Expansion of the secondary injury following primary spinal cord injury is a major pathological event that increases destruction in the spinal cord, so measures to reduce secondary injury are needed. Our previous study...Expansion of the secondary injury following primary spinal cord injury is a major pathological event that increases destruction in the spinal cord, so measures to reduce secondary injury are needed. Our previous study demonstrated that, at the front of the expanding secondary injury in the spinal cord, there is an ischemic area in which many neurons can still be rescued. Therefore, enhancement of blood circulation in the cord may be helpful, and indeed, we found that a traditional Chinese medicine, shu-xue-tong, efficiently reduces the secondary injury. The aim of the present study was to investigate the effect of reducing fibrinogen with Batroxobin, a drug widely used clinically for ischemia, in rats with spinal cord contusion. We found that both 2 and 4 Batroxobin units （BU）/kg efficiently decreased the plasma fibrinogen, and 2 BU/kg significantly increased spinal blood flow, enhanced neuronal survival, mitigated astrocyte and microglia activation, and improved locomotor recovery. However, 4 BU/kg had no effect on the secondary spinal cord injury. These data suggest that Batroxobin has multiple beneficial effects on spinal cord injury, indicating a potential clinical application.展开更多
Metabolic changes in rats with photochemically induced cerebral infarction and the effects of batroxobin were investigated 1, 3, 5 and 7 days after infarction by means of magnetic resonance imaging (MRI), 1H- and 31P-...Metabolic changes in rats with photochemically induced cerebral infarction and the effects of batroxobin were investigated 1, 3, 5 and 7 days after infarction by means of magnetic resonance imaging (MRI), 1H- and 31P-magnetic resonance spectroscopy (MRS). A region of T2 hyperintensity was observed in left temporal neocortex in infarction group and batroxobin group 1, 3, 5 and 7 days after infarction. The volume of the region gradually decreased from 1 day to 7 days after infarction. The ratio of NAA/Cho + Cr in the region of T2 hyperintensity in the infarction group was significantly lower than that in the corresponding region in the sham-operated group 3, 5 and 7 days after infarction respectively (P展开更多
To study the changes of the expression of growth-associated protein-43 (GAP-43) and pathology in temporal infarction of rats photochemically induced and the effects of batroxobin. METHODS: Immunohistochemical techniqu...To study the changes of the expression of growth-associated protein-43 (GAP-43) and pathology in temporal infarction of rats photochemically induced and the effects of batroxobin. METHODS: Immunohistochemical technique and hematoxylin-eosin stain was used to show the changes of the expression of GAP-43 and pathology. RESULTS: In infarction group, GAP-43 expression was markedly increased on the infarction and surrounding tissues at 24 h cerebral infarction. The expression reached peak level at 72 h after cerebral infarction and was decreased at 7 d after cerebral infarction. However, in batroxobin-treated group, GAP-43 expression was increased and the pathological changes were much slight as compared with infarction group. CONCLUSION: The expression of GAP-43 increases in infarction of temporal neocortex and batroxobin promotes the expression of GAP-43 and ameliorates the pathological changes in infarction of temporal neocortex.展开更多
The effect of Batroxobin expression of neural cell adhesion molecule (NCAM) in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemical metho...The effect of Batroxobin expression of neural cell adhesion molecule (NCAM) in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemical methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats and at the same time NCAM expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of NCAM immune reactive cells of Batroxobin-treated rats was more than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats and the regulation of the expression of NCAM is probably related to the neuroprotective mechanism.展开更多
We have found that Batroxobin plays a protective role in ischemic brain injury, which attracted us to investigate the effect of Batroxobin on apoptosis of neurons during cerebral ischemia and reperfusion. The apoptoti...We have found that Batroxobin plays a protective role in ischemic brain injury, which attracted us to investigate the effect of Batroxobin on apoptosis of neurons during cerebral ischemia and reperfusion. The apoptotic cells in ischemic rat brains at different reperfusion intervals were tested with method of TdT-mediated dUTP-DIG nick end labeling (TUNEL) and the effect of Batroxobin on the apoptosis of neurons was studied in left middle cerebral artery (LMCA) occlusion and reperfusion in rat models (n = 18). The results showed that few scattered apoptosis cells were observed in right cerebral hemispheres after LMCA occlusion and reperfusion, and that a lot of apoptosis cells were found in left ischemic cortex and caudoputamen at 12 h reperfusion, and they reached peak at 24 h-48 h reperfusion. However, in the rats pretreated with Batroxobin, the number of apoptosis cells in left cerebral cortex and caudoputamen reduced significantly and the neuronal damage was much milder at 24 h reperfusion than that of saline-treated rats. The results indicate that administration of Batroxobin may reduce the apoptosis of neurons induced by cerebral ischemia and reperfusion and afford significant cerebroprotection in the model of focal cerebral ischemia and reperfusion.展开更多
The effect of Batroxobin on spatial memory disorder of left temporal ischemic rats and the expression of HSP32 and HSP70 were investigated with Morri`s water maze and immunohistochemistry methods. The results show... The effect of Batroxobin on spatial memory disorder of left temporal ischemic rats and the expression of HSP32 and HSP70 were investigated with Morri`s water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats in searching a goal were significantly longer than those of the sham-operated rats and at the same time HSP32 and HSP70 expression of left temporal ischemic region in rats was significantly increased as compared with the sham-operated rats. However, the mean reaction time and distance of the Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of HSP32 and HSP70 immune reactive cells of Batroxobin-treated rats was also less than that of the ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats; and the down-regulation of the expression of HSP32 and HSP70 is probably related to the attenuation of ischemic injury.展开更多
Recombinant batroxobin(S3101)is a thrombin-like serine protease that binds to fibrinogen or is taken up by the reticuloendothelial system.A literature survey showed no adequate method that could determine sufficient c...Recombinant batroxobin(S3101)is a thrombin-like serine protease that binds to fibrinogen or is taken up by the reticuloendothelial system.A literature survey showed no adequate method that could determine sufficient concentrations to evaluate pharmacokinetic parameters for phase I clinical studies.Therefore,a sensitive method is urgently needed to support the clinical pharmacokinetic evaluation of S3101.In this study,a sensitive bioanalytical method was developed and validated,using a Quanterix single molecular array(Simoa)assay.Moreover,to thoroughly assess the platform,enzyme-linked immunosorbent assay and electrochemiluminescence assay were also developed,and their performance was compared with that of this novel technology platform.The assay was validated in compliance with the current guidelines.Measurements with the Simoa assay were precise and accurate,presenting a valid assay range from 6.55 to 4000 pg/mL.The intra-and inter-run accuracy and precision were within-19.3%to 15.3%and 5.5%to 17.0%,respectively.S3101 was stable in human serum for 280 days at-20℃and-70℃,for 2 h prior to pre-treatment and 24 h post pre-treatment at room temperature(22℃-28℃),respectively,and after five and two freeze-thaw cycles at-70℃and-20oC,respectively.The Simoa assay also demonstrated sufficient dilution linearity,assay sensitivity,and parallelism for quantifying S3101 in human serum.The Simoa assay is a sensitive and adequate method for evaluating the pharmacokinetic parameters of S3101 in human serum.展开更多
Objective:The aim of the study was to explore the therapeutic efficacy and safety of batroxobin in patients with primary hepatic carcinoma(PHC) and the advantages of transcatheter arterial perfusion of batroxobin comb...Objective:The aim of the study was to explore the therapeutic efficacy and safety of batroxobin in patients with primary hepatic carcinoma(PHC) and the advantages of transcatheter arterial perfusion of batroxobin combined with transcatheter arterial chemoembolization(TACE).Methods:Forty patients with PHC were randomized into experimental group(transcatheter arterial perfusion of batroxobin combined with TACE treatment,20 patients) and control group(TACE alone group,20 patients).The patients were followed up and the data were recorded,compared and analyzed.Results:(1) Compared with the control group,the FIB level in the experimental group was significantly decreased at the first month after treatment(P < 0.05).(2) The baseline of the tumor was shortened in both groups after the treatment.There was a significant difference between the two groups at different time intervals(P < 0.05).(3) After the treatment,there was a significant difference of progression-free survival(PFS) levels between the two groups(t =2.877,P < 0.05).(4) The incidence of metastasis were 5.0%(1/20) in both groups at 6 months after treatment,and that after one year was 10.0%(2/20) in the experimental group and 25.0%(5/20) in the control group.However,the difference was not significant(χ2 = 0.693,P > 0.05).Conclusion:Batroxobin can rapidly and effectively decrease the FIB level of the PHC cases.Therefore it may be used as an effective and safe adjuvant drug for the treatment of primary hepatic carcinomas.Transcatheter arterial perfusion of batroxobin combined with TACE therapy has advantages in comparison with TACE alone therapy.It could be taken as a new therapeutic regimen in the PHC treatment.展开更多
Objective: To investigate the effects of ginaton combined with batroxobin on oxidative stress, hemodynamics and coagulation in patients with sudden hearing loss. Methods: According to random data table method, 100 cas...Objective: To investigate the effects of ginaton combined with batroxobin on oxidative stress, hemodynamics and coagulation in patients with sudden hearing loss. Methods: According to random data table method, 100 cases of sudden hearing loss were randomly divided into the control group (n=50) and observation group (n=50), patients in the control group were given batroxobin treatment, the observation group received ginaton combined with batroxobin theraphy.The levels of oxidative stress, hemodynamics and coagulation were compared between the two groups before and after treatment. Results: The levels of WBV, HCT, PV, APTT, PT, TT, PF, SOD, LPO in the two groups before treatment were not statistically significant. After treatment, the levels of WBV, PV in the control group and observation group were respectively (5.33±0.62) mPa?s, (1.73±0.59) mPa?s and (4.07±0.55) mPa?s, (1.32±0.41) mPa?s, which were significantly lower than those before treatment, and after treatment in the observation group the levels of WBV, PV were significantly lower than the control group;After treatment, the levels of APTT, PT, TT, PF in the control group and observation group were respectively (43.75±6.15) s, (18.23±2.02) s, (15.38±2.51) s, (58.61±12.96) μg/L and (53.68±7.16) s, (24.67±4.35) s, (22.51±4.85) s, (41.47±8.63) μg/L, compared with those in the same group before treatment, the levels of APTT, PT and TT were significantly increased, PF level was significantly decreased, and in the observation group APTT, PT and TT levels were significantly higher and PF level was significantly lower than that in the control group. After treatment, the levels of SOD, LPO in the control group and observation group were respectively (101.78±10.53) nu/L, (5.91±0.95) mmol/L and (110.07±12.62) nu/L, (4.68±1.02) mmol/L compared with those in the same group before treatment, the level of SOD were significantly increased, the level of LPO level was significantly decreased, and in the observation group LPO level was significantly lower and SOD level was significantly higher than that in the control group. Conclusion Compared with the use of batroxobin alone, Ginaton combined with batroxobin can better reduce the stress response, improve hemodynamics and coagulation in patients with sudden hearing loss.展开更多
BACKGROUND： Batroxobin has been found to have protective effect on cerebral ischemia-reperfusion, and cardiopulmonary resuscitation （CPR） is the common cause of global brain ischemia-reperfusion. OBJECTIVE： To obs...BACKGROUND： Batroxobin has been found to have protective effect on cerebral ischemia-reperfusion, and cardiopulmonary resuscitation （CPR） is the common cause of global brain ischemia-reperfusion. OBJECTIVE： To observe the effect of Batroxobin on the morphological results of cerebral cortex and hippocampus in rabbit models of CPR, and the changes of serum concentration of tumor necrosis factor alpha （TNF- α ） after CPR. DESIGN： A randomized controlled observation. SETTING： Laboratory of the Department of Bums, Changhai Hospital affiliated to the Second Military Medical University of Chinese PLA. MATERIALS： Thirty healthy New Zealand rabbits of 2.5 - 3.0 kg, either male or female, were used. Kits for TNF- α determination were provided by LIFEKEY BioMeditech Company （USA）. METHODS： The experiments were carried out in the laboratory of Department of Bums, Changhai Hospital from February 2001 to January 2002. The 32 rabbits were randomly divided into sham-operated group （n=8）, conventional resuscitation group （n=12） and Batroxobin-treated group （n=12）. The animals in the conventional resuscitation group and Batroxobin-treated group were anesthetized, then induced into modified Pittsburg＇s model of mechanical ventricular fibrillation. Sham-operated group was discharged on the chest wall, which did not cause ventricular fibrillation. Conventional resuscitation group and Batroxobin-treated group were exposed to 6 minutes of cardiac arrest induced by ventricular fibrillation, then the resuscitation began. A dosage of 0.3 Bu/kg of Batroxobin was administered to the rabbits in the Batroxobin-treated group at the beginning of resuscitation. Blood sample was collected at 4 and 12 hours after CPR to determine the concentration of TNF- α in serum. After the second blood collection, brain tissue was taken out immediately, and the forms of nerve cells in cerebral cortex and hippocampal CAl region were observed under light microscope. MAIN OUTCOME MEASURES： ① TNF- α concentration in serum at 4 and 12 hours after CPR; ② Forms of nerve cells in cerebral cortex and hippocampal CAI region at 12 hours after CPR. RESULTS： All the 31 New Zealand rabbits were involved in the analysis of results. ①TNF-α concentration in serum： At 4 hours after CPR, the TNF-α concentrations in serum in the conventional resuscitation group and Batroxobin-treated group [（5.947±2.366）, （5.122±2.521） ng/L] were significantly higher than that in the sham-operated group [（2.604±1.623） ng/L, P 〈 0.05]. At 12 hours after CPR, the TNF- α concentration in serum in the conventional resuscitation group was （7.770±3.121） ng/L, it was significantly higher than that at 4 hours （P 〈 0.05）, also significantly higher than that in the Batroxobin-treated group [（5.425±2.280） ng/L, P 〈 0.05]. ② Forms of nerve cells： In the sham-operated group, no abnormality was found in the hippocampal CAI region and cerebral cortex. In the conventional resuscitation group, the pyramidal cells in hippocampal CAI region were lined up in disorders, and edema, puff, vacuolization, nucleus concentration and anachromasis were also observed appeared; Edema of nerve cells, vacuole, pyknosis appeared in cerebral cortex; microthrombosis appeared in some blood capillaries. As compared with the conventional resuscitation group, cellular edema was relieved and pyknosis of nerve cells were obviously reduced, and no microthrombosis was found in hippocampal CAI region and cerebral cortex in the Batroxobin-treated group. CONCLUSION： Batroxobin have neuroprotective effect on CPR rabbits, and may inhibit the excessive increase of TNF- α concentration in serum.展开更多
The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that...The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats, and at the same time c-Jun expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of c-Jun immune reactive cells of Batroxobin-treated rats was also less than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder in temporal ischemic rats, and the down-regulation of the expression of c-Jun is probably related to the neuroprotective mechanism.展开更多
Batroxobin,the thrombin-like enzyme,is used for therapeutic defibrination. We have found that batroxobin has good therapeutic effect in ischemic reperfusion rats and clinical practices in vivo. But we have not studied...Batroxobin,the thrombin-like enzyme,is used for therapeutic defibrination. We have found that batroxobin has good therapeutic effect in ischemic reperfusion rats and clinical practices in vivo. But we have not studied the neuroprotective effect of batroxobin on anoxic hippocampal neurons in vitro. The purpose of this study was to obtain further information on the mechanism of the batroxobin-induced neuroprotection and examine the neuroprotective effect on neurons exposed to anoxia. The effect of batroxobin on anoxic damages in cultured hippocampal neurons of neonatal rats was investigated by using morphological changes and heat shock protein 70Kd (Hsp70) immunoreactive expression as indicators. The results indicate that batroxobin, besides its defibrination, may have a direct neuroprotective effect on anoxic damage of hippocampal neurons.展开更多
Objective: To study the effects of combined use of Batroxobin and Ginkgo Leaf Extract and Dipyridamole Injection on hemodynamics, coagulation function, fibrinolytic function and related factors in patients with sudden...Objective: To study the effects of combined use of Batroxobin and Ginkgo Leaf Extract and Dipyridamole Injection on hemodynamics, coagulation function, fibrinolytic function and related factors in patients with sudden deafness. Methods: A total of 94 patients with sudden deafness in our hospital were selected, and divided them into control group and observation group randomly, 47 cases in each group. All patients were given 10BU batroxobin injection intravenous drip after admission every other day;And the patients of observation group were given intravenous drip of 30ml ginkgo-damole injection, 1 time a day. The hemodynamics, coagulation function, fibrinolytic function and related factors were detected and compared between the two groups before and after treatment. Results: Before treatment, there was no statistical difference in hemodynamics, coagulation function, fibrinolytic function and related factors between the two groups;After treatment, the levels of WBV and PV in the control group was (5.21±0.58) mPa/s and (1.78±0.32) mPa/s, and the observation group was (4.13±0.47) mPa/s and (1.31±0.26) mPa/s, compared with the same group before treatment, there were statistical difference, and there was also statistical difference between the two groups;The levels of PT, APTT, TT and PF was (19.22±3.98) s, (43.57±9.88) s, (15.64±3.27) s and (58.22±10.58) μg/L, and the observation group was (23.97±4.82) s, (52.49±10.38) s, (20.59±4.15) s and (41.03±8.46) μg/L, compared with the same group before treatment, there were statistical difference, and there was also statistical difference between the two groups;The levels of Fib, D-dimer and FDP was (4.52±0.93) g/L, (6.53±1.88) mg/L and (8.17±2.34)μg/mL, and the observation group was (3.13±0.75 g/L, (9.75±2.14) mg/L, (13.52±2.58) μg/mL, compared with the same group before treatment, there were statistical difference, and there was also statistical difference between the two groups;The serum levels of ET, NO and SOD was (66.92±5.87) ρg/mL, (48.75±7.61) μmol/L, (95.01±12.38) NU/mL, and the observation group was (63.97±5.24) ρg/mL, (43.11±6.83) μmol/L, (104.79±13.15) NU/mL, compared with the same group before treatment, there were statistical difference, and there was also statistical difference between the two groups. Conclusion: The treatment of patients with sudden deafness using batroxobin combine with ginkgo-damole injection, can improve the hemodynamics, coagulation function, fibrinolytic function of patients, decrease the serum levels of ET and NO, improve the levels of SOD, the effect is curative, it's worthy of clinical application.展开更多
Background Batroxobin (BX),a serine protease used in defibrinogenation and thrombolysis,also has an effect on c-fos gene and growth factor. This study attempted to determine the effects of BX on the proliferation of v...Background Batroxobin (BX),a serine protease used in defibrinogenation and thrombolysis,also has an effect on c-fos gene and growth factor. This study attempted to determine the effects of BX on the proliferation of vascular smooth muscle cells (VSMCs) and calcium metabolism. Methods VSMCs were treated with BX at concentrations of 0.1,0.3,or 1.0 mmol/L and cell numbers were determined at 0,24,48,and 72 hours. Intracellular calcium concentration ([Ca 2+ ]_i) was measured using direct fluorescence methods. Results BX was found to suppress proliferation of VSMCs in a dose-dependent fashion with inhibition rates of 18% and 31% by 48 and 72 hours,respectively. In addition,BX decreases basal [Ca 2+ ]_i significantly. The basal level in untreated cells was 162.7±33.8 nmol/L,and decreased to 131.5±27.7 nmol/L,128.3±28.5 nmol/L,and 125.6±34.3 nmol/L with the three concentrations of BX,respectively. Noradrenaline (NE)-induced [Ca 2+ ]_i stimulation was also attenuated by BX (0.1 mmol/L BX,20%±8% inhibition; 0.3 mmol/L BX,54%±11% inhibition; 1.0 mmol/L BX,62%±15% inhibition). The ability of NE to stimulate [Ca 2+ ]_i was attenuated in cultures in Ca 2+ -free medium,as was the ability of BX to blunt NE-induced stimulation. Conclusion These findings demonstrate that BX can effectively inhibit proliferation of VSMCs,probably by blocking the release and uptake of Ca 2+ ,thus influencing [Ca 2+ ]_i.展开更多
基金supported by grants from the National Natural Science Foundation of China (81072600 and 31271583)
文摘Expansion of the secondary injury following primary spinal cord injury is a major pathological event that increases destruction in the spinal cord, so measures to reduce secondary injury are needed. Our previous study demonstrated that, at the front of the expanding secondary injury in the spinal cord, there is an ischemic area in which many neurons can still be rescued. Therefore, enhancement of blood circulation in the cord may be helpful, and indeed, we found that a traditional Chinese medicine, shu-xue-tong, efficiently reduces the secondary injury. The aim of the present study was to investigate the effect of reducing fibrinogen with Batroxobin, a drug widely used clinically for ischemia, in rats with spinal cord contusion. We found that both 2 and 4 Batroxobin units （BU）/kg efficiently decreased the plasma fibrinogen, and 2 BU/kg significantly increased spinal blood flow, enhanced neuronal survival, mitigated astrocyte and microglia activation, and improved locomotor recovery. However, 4 BU/kg had no effect on the secondary spinal cord injury. These data suggest that Batroxobin has multiple beneficial effects on spinal cord injury, indicating a potential clinical application.
文摘Metabolic changes in rats with photochemically induced cerebral infarction and the effects of batroxobin were investigated 1, 3, 5 and 7 days after infarction by means of magnetic resonance imaging (MRI), 1H- and 31P-magnetic resonance spectroscopy (MRS). A region of T2 hyperintensity was observed in left temporal neocortex in infarction group and batroxobin group 1, 3, 5 and 7 days after infarction. The volume of the region gradually decreased from 1 day to 7 days after infarction. The ratio of NAA/Cho + Cr in the region of T2 hyperintensity in the infarction group was significantly lower than that in the corresponding region in the sham-operated group 3, 5 and 7 days after infarction respectively (P
文摘To study the changes of the expression of growth-associated protein-43 (GAP-43) and pathology in temporal infarction of rats photochemically induced and the effects of batroxobin. METHODS: Immunohistochemical technique and hematoxylin-eosin stain was used to show the changes of the expression of GAP-43 and pathology. RESULTS: In infarction group, GAP-43 expression was markedly increased on the infarction and surrounding tissues at 24 h cerebral infarction. The expression reached peak level at 72 h after cerebral infarction and was decreased at 7 d after cerebral infarction. However, in batroxobin-treated group, GAP-43 expression was increased and the pathological changes were much slight as compared with infarction group. CONCLUSION: The expression of GAP-43 increases in infarction of temporal neocortex and batroxobin promotes the expression of GAP-43 and ameliorates the pathological changes in infarction of temporal neocortex.
文摘The effect of Batroxobin expression of neural cell adhesion molecule (NCAM) in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemical methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats and at the same time NCAM expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of NCAM immune reactive cells of Batroxobin-treated rats was more than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats and the regulation of the expression of NCAM is probably related to the neuroprotective mechanism.
文摘We have found that Batroxobin plays a protective role in ischemic brain injury, which attracted us to investigate the effect of Batroxobin on apoptosis of neurons during cerebral ischemia and reperfusion. The apoptotic cells in ischemic rat brains at different reperfusion intervals were tested with method of TdT-mediated dUTP-DIG nick end labeling (TUNEL) and the effect of Batroxobin on the apoptosis of neurons was studied in left middle cerebral artery (LMCA) occlusion and reperfusion in rat models (n = 18). The results showed that few scattered apoptosis cells were observed in right cerebral hemispheres after LMCA occlusion and reperfusion, and that a lot of apoptosis cells were found in left ischemic cortex and caudoputamen at 12 h reperfusion, and they reached peak at 24 h-48 h reperfusion. However, in the rats pretreated with Batroxobin, the number of apoptosis cells in left cerebral cortex and caudoputamen reduced significantly and the neuronal damage was much milder at 24 h reperfusion than that of saline-treated rats. The results indicate that administration of Batroxobin may reduce the apoptosis of neurons induced by cerebral ischemia and reperfusion and afford significant cerebroprotection in the model of focal cerebral ischemia and reperfusion.
文摘 The effect of Batroxobin on spatial memory disorder of left temporal ischemic rats and the expression of HSP32 and HSP70 were investigated with Morri`s water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats in searching a goal were significantly longer than those of the sham-operated rats and at the same time HSP32 and HSP70 expression of left temporal ischemic region in rats was significantly increased as compared with the sham-operated rats. However, the mean reaction time and distance of the Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of HSP32 and HSP70 immune reactive cells of Batroxobin-treated rats was also less than that of the ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats; and the down-regulation of the expression of HSP32 and HSP70 is probably related to the attenuation of ischemic injury.
文摘Recombinant batroxobin(S3101)is a thrombin-like serine protease that binds to fibrinogen or is taken up by the reticuloendothelial system.A literature survey showed no adequate method that could determine sufficient concentrations to evaluate pharmacokinetic parameters for phase I clinical studies.Therefore,a sensitive method is urgently needed to support the clinical pharmacokinetic evaluation of S3101.In this study,a sensitive bioanalytical method was developed and validated,using a Quanterix single molecular array(Simoa)assay.Moreover,to thoroughly assess the platform,enzyme-linked immunosorbent assay and electrochemiluminescence assay were also developed,and their performance was compared with that of this novel technology platform.The assay was validated in compliance with the current guidelines.Measurements with the Simoa assay were precise and accurate,presenting a valid assay range from 6.55 to 4000 pg/mL.The intra-and inter-run accuracy and precision were within-19.3%to 15.3%and 5.5%to 17.0%,respectively.S3101 was stable in human serum for 280 days at-20℃and-70℃,for 2 h prior to pre-treatment and 24 h post pre-treatment at room temperature(22℃-28℃),respectively,and after five and two freeze-thaw cycles at-70℃and-20oC,respectively.The Simoa assay also demonstrated sufficient dilution linearity,assay sensitivity,and parallelism for quantifying S3101 in human serum.The Simoa assay is a sensitive and adequate method for evaluating the pharmacokinetic parameters of S3101 in human serum.
基金Supported by a grant from the Sciences and Technology Foundation of Guangdong Province (No. 73128)
文摘Objective:The aim of the study was to explore the therapeutic efficacy and safety of batroxobin in patients with primary hepatic carcinoma(PHC) and the advantages of transcatheter arterial perfusion of batroxobin combined with transcatheter arterial chemoembolization(TACE).Methods:Forty patients with PHC were randomized into experimental group(transcatheter arterial perfusion of batroxobin combined with TACE treatment,20 patients) and control group(TACE alone group,20 patients).The patients were followed up and the data were recorded,compared and analyzed.Results:(1) Compared with the control group,the FIB level in the experimental group was significantly decreased at the first month after treatment(P < 0.05).(2) The baseline of the tumor was shortened in both groups after the treatment.There was a significant difference between the two groups at different time intervals(P < 0.05).(3) After the treatment,there was a significant difference of progression-free survival(PFS) levels between the two groups(t =2.877,P < 0.05).(4) The incidence of metastasis were 5.0%(1/20) in both groups at 6 months after treatment,and that after one year was 10.0%(2/20) in the experimental group and 25.0%(5/20) in the control group.However,the difference was not significant(χ2 = 0.693,P > 0.05).Conclusion:Batroxobin can rapidly and effectively decrease the FIB level of the PHC cases.Therefore it may be used as an effective and safe adjuvant drug for the treatment of primary hepatic carcinomas.Transcatheter arterial perfusion of batroxobin combined with TACE therapy has advantages in comparison with TACE alone therapy.It could be taken as a new therapeutic regimen in the PHC treatment.
文摘Objective: To investigate the effects of ginaton combined with batroxobin on oxidative stress, hemodynamics and coagulation in patients with sudden hearing loss. Methods: According to random data table method, 100 cases of sudden hearing loss were randomly divided into the control group (n=50) and observation group (n=50), patients in the control group were given batroxobin treatment, the observation group received ginaton combined with batroxobin theraphy.The levels of oxidative stress, hemodynamics and coagulation were compared between the two groups before and after treatment. Results: The levels of WBV, HCT, PV, APTT, PT, TT, PF, SOD, LPO in the two groups before treatment were not statistically significant. After treatment, the levels of WBV, PV in the control group and observation group were respectively (5.33±0.62) mPa?s, (1.73±0.59) mPa?s and (4.07±0.55) mPa?s, (1.32±0.41) mPa?s, which were significantly lower than those before treatment, and after treatment in the observation group the levels of WBV, PV were significantly lower than the control group;After treatment, the levels of APTT, PT, TT, PF in the control group and observation group were respectively (43.75±6.15) s, (18.23±2.02) s, (15.38±2.51) s, (58.61±12.96) μg/L and (53.68±7.16) s, (24.67±4.35) s, (22.51±4.85) s, (41.47±8.63) μg/L, compared with those in the same group before treatment, the levels of APTT, PT and TT were significantly increased, PF level was significantly decreased, and in the observation group APTT, PT and TT levels were significantly higher and PF level was significantly lower than that in the control group. After treatment, the levels of SOD, LPO in the control group and observation group were respectively (101.78±10.53) nu/L, (5.91±0.95) mmol/L and (110.07±12.62) nu/L, (4.68±1.02) mmol/L compared with those in the same group before treatment, the level of SOD were significantly increased, the level of LPO level was significantly decreased, and in the observation group LPO level was significantly lower and SOD level was significantly higher than that in the control group. Conclusion Compared with the use of batroxobin alone, Ginaton combined with batroxobin can better reduce the stress response, improve hemodynamics and coagulation in patients with sudden hearing loss.
文摘BACKGROUND： Batroxobin has been found to have protective effect on cerebral ischemia-reperfusion, and cardiopulmonary resuscitation （CPR） is the common cause of global brain ischemia-reperfusion. OBJECTIVE： To observe the effect of Batroxobin on the morphological results of cerebral cortex and hippocampus in rabbit models of CPR, and the changes of serum concentration of tumor necrosis factor alpha （TNF- α ） after CPR. DESIGN： A randomized controlled observation. SETTING： Laboratory of the Department of Bums, Changhai Hospital affiliated to the Second Military Medical University of Chinese PLA. MATERIALS： Thirty healthy New Zealand rabbits of 2.5 - 3.0 kg, either male or female, were used. Kits for TNF- α determination were provided by LIFEKEY BioMeditech Company （USA）. METHODS： The experiments were carried out in the laboratory of Department of Bums, Changhai Hospital from February 2001 to January 2002. The 32 rabbits were randomly divided into sham-operated group （n=8）, conventional resuscitation group （n=12） and Batroxobin-treated group （n=12）. The animals in the conventional resuscitation group and Batroxobin-treated group were anesthetized, then induced into modified Pittsburg＇s model of mechanical ventricular fibrillation. Sham-operated group was discharged on the chest wall, which did not cause ventricular fibrillation. Conventional resuscitation group and Batroxobin-treated group were exposed to 6 minutes of cardiac arrest induced by ventricular fibrillation, then the resuscitation began. A dosage of 0.3 Bu/kg of Batroxobin was administered to the rabbits in the Batroxobin-treated group at the beginning of resuscitation. Blood sample was collected at 4 and 12 hours after CPR to determine the concentration of TNF- α in serum. After the second blood collection, brain tissue was taken out immediately, and the forms of nerve cells in cerebral cortex and hippocampal CAl region were observed under light microscope. MAIN OUTCOME MEASURES： ① TNF- α concentration in serum at 4 and 12 hours after CPR; ② Forms of nerve cells in cerebral cortex and hippocampal CAI region at 12 hours after CPR. RESULTS： All the 31 New Zealand rabbits were involved in the analysis of results. ①TNF-α concentration in serum： At 4 hours after CPR, the TNF-α concentrations in serum in the conventional resuscitation group and Batroxobin-treated group [（5.947±2.366）, （5.122±2.521） ng/L] were significantly higher than that in the sham-operated group [（2.604±1.623） ng/L, P 〈 0.05]. At 12 hours after CPR, the TNF- α concentration in serum in the conventional resuscitation group was （7.770±3.121） ng/L, it was significantly higher than that at 4 hours （P 〈 0.05）, also significantly higher than that in the Batroxobin-treated group [（5.425±2.280） ng/L, P 〈 0.05]. ② Forms of nerve cells： In the sham-operated group, no abnormality was found in the hippocampal CAI region and cerebral cortex. In the conventional resuscitation group, the pyramidal cells in hippocampal CAI region were lined up in disorders, and edema, puff, vacuolization, nucleus concentration and anachromasis were also observed appeared; Edema of nerve cells, vacuole, pyknosis appeared in cerebral cortex; microthrombosis appeared in some blood capillaries. As compared with the conventional resuscitation group, cellular edema was relieved and pyknosis of nerve cells were obviously reduced, and no microthrombosis was found in hippocampal CAI region and cerebral cortex in the Batroxobin-treated group. CONCLUSION： Batroxobin have neuroprotective effect on CPR rabbits, and may inhibit the excessive increase of TNF- α concentration in serum.
文摘The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats, and at the same time c-Jun expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of c-Jun immune reactive cells of Batroxobin-treated rats was also less than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder in temporal ischemic rats, and the down-regulation of the expression of c-Jun is probably related to the neuroprotective mechanism.
文摘Batroxobin,the thrombin-like enzyme,is used for therapeutic defibrination. We have found that batroxobin has good therapeutic effect in ischemic reperfusion rats and clinical practices in vivo. But we have not studied the neuroprotective effect of batroxobin on anoxic hippocampal neurons in vitro. The purpose of this study was to obtain further information on the mechanism of the batroxobin-induced neuroprotection and examine the neuroprotective effect on neurons exposed to anoxia. The effect of batroxobin on anoxic damages in cultured hippocampal neurons of neonatal rats was investigated by using morphological changes and heat shock protein 70Kd (Hsp70) immunoreactive expression as indicators. The results indicate that batroxobin, besides its defibrination, may have a direct neuroprotective effect on anoxic damage of hippocampal neurons.
文摘Objective: To study the effects of combined use of Batroxobin and Ginkgo Leaf Extract and Dipyridamole Injection on hemodynamics, coagulation function, fibrinolytic function and related factors in patients with sudden deafness. Methods: A total of 94 patients with sudden deafness in our hospital were selected, and divided them into control group and observation group randomly, 47 cases in each group. All patients were given 10BU batroxobin injection intravenous drip after admission every other day;And the patients of observation group were given intravenous drip of 30ml ginkgo-damole injection, 1 time a day. The hemodynamics, coagulation function, fibrinolytic function and related factors were detected and compared between the two groups before and after treatment. Results: Before treatment, there was no statistical difference in hemodynamics, coagulation function, fibrinolytic function and related factors between the two groups;After treatment, the levels of WBV and PV in the control group was (5.21±0.58) mPa/s and (1.78±0.32) mPa/s, and the observation group was (4.13±0.47) mPa/s and (1.31±0.26) mPa/s, compared with the same group before treatment, there were statistical difference, and there was also statistical difference between the two groups;The levels of PT, APTT, TT and PF was (19.22±3.98) s, (43.57±9.88) s, (15.64±3.27) s and (58.22±10.58) μg/L, and the observation group was (23.97±4.82) s, (52.49±10.38) s, (20.59±4.15) s and (41.03±8.46) μg/L, compared with the same group before treatment, there were statistical difference, and there was also statistical difference between the two groups;The levels of Fib, D-dimer and FDP was (4.52±0.93) g/L, (6.53±1.88) mg/L and (8.17±2.34)μg/mL, and the observation group was (3.13±0.75 g/L, (9.75±2.14) mg/L, (13.52±2.58) μg/mL, compared with the same group before treatment, there were statistical difference, and there was also statistical difference between the two groups;The serum levels of ET, NO and SOD was (66.92±5.87) ρg/mL, (48.75±7.61) μmol/L, (95.01±12.38) NU/mL, and the observation group was (63.97±5.24) ρg/mL, (43.11±6.83) μmol/L, (104.79±13.15) NU/mL, compared with the same group before treatment, there were statistical difference, and there was also statistical difference between the two groups. Conclusion: The treatment of patients with sudden deafness using batroxobin combine with ginkgo-damole injection, can improve the hemodynamics, coagulation function, fibrinolytic function of patients, decrease the serum levels of ET and NO, improve the levels of SOD, the effect is curative, it's worthy of clinical application.
基金ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina (No 3 0 0 0 0 163 )
文摘Background Batroxobin (BX),a serine protease used in defibrinogenation and thrombolysis,also has an effect on c-fos gene and growth factor. This study attempted to determine the effects of BX on the proliferation of vascular smooth muscle cells (VSMCs) and calcium metabolism. Methods VSMCs were treated with BX at concentrations of 0.1,0.3,or 1.0 mmol/L and cell numbers were determined at 0,24,48,and 72 hours. Intracellular calcium concentration ([Ca 2+ ]_i) was measured using direct fluorescence methods. Results BX was found to suppress proliferation of VSMCs in a dose-dependent fashion with inhibition rates of 18% and 31% by 48 and 72 hours,respectively. In addition,BX decreases basal [Ca 2+ ]_i significantly. The basal level in untreated cells was 162.7±33.8 nmol/L,and decreased to 131.5±27.7 nmol/L,128.3±28.5 nmol/L,and 125.6±34.3 nmol/L with the three concentrations of BX,respectively. Noradrenaline (NE)-induced [Ca 2+ ]_i stimulation was also attenuated by BX (0.1 mmol/L BX,20%±8% inhibition; 0.3 mmol/L BX,54%±11% inhibition; 1.0 mmol/L BX,62%±15% inhibition). The ability of NE to stimulate [Ca 2+ ]_i was attenuated in cultures in Ca 2+ -free medium,as was the ability of BX to blunt NE-induced stimulation. Conclusion These findings demonstrate that BX can effectively inhibit proliferation of VSMCs,probably by blocking the release and uptake of Ca 2+ ,thus influencing [Ca 2+ ]_i.
