Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to i...Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion.Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins,Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion,enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group.Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion,expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl-2/Bax, especially in membrane fraction.展开更多
AIM: To explore the pathophysiological significance of delayed type hypersensitivity (DTH) reaction in mouse gastrointestinal tract induced by an allergen 2,4-dinitrochlorobenzene (DNCB).METHODS: BALB/c mice were rand...AIM: To explore the pathophysiological significance of delayed type hypersensitivity (DTH) reaction in mouse gastrointestinal tract induced by an allergen 2,4-dinitrochlorobenzene (DNCB).METHODS: BALB/c mice were randomly divided into control and DTH1-6 groups. After sensitized by DNCB smeared on the abdominal skin, the mice were challenged with DNCB by gavage or enema. The weight, stool viscosity and hematochezia were observed and accumulated as disease active index (DAI) score; the gastrointestinal motility was represented by active charcoal propulsion rate;the colon pathological score was achieved by macropathology and HE staining of section prepared for microscopy; and the leukocyte migration inhibitory factor (1MIF) activity was determined by indirect capillary assay of the absorbance (A) of migrated leukocytes.RESULTS: Active charcoal propulsion rates of small intestine in the DNCB gavages groups were significantly higher than that in the control group (P<0.01). The DAI scores and pathological score in DNCB enema groups were also higher than that in the control group (P<0.05), and there were significant rises in LMIF activity in DNCB enemagroups as compared with control groups (P<0.01).CONCLUSION: Mouse gastrointestinal DTH reaction could be induced by DNCB, which might facilitate the mechanism underlying the ulcerative colitis.展开更多
AIM: To illustrate the pathophysiological role of metallothionein (MT) in gastric ulcer induced by stress. METHODS: Wistar rats underwent water-immersionrestraint (WIR) stress, ZnSO4 (an MT inducer) treatment, WIR+ZnS...AIM: To illustrate the pathophysiological role of metallothionein (MT) in gastric ulcer induced by stress. METHODS: Wistar rats underwent water-immersionrestraint (WIR) stress, ZnSO4 (an MT inducer) treatment, WIR+ZnSO4 or WIR+MT, and the ulcer index (UI) was estimated in excised stomach and liver tissues. The mRNA level of gastric MT was determined by semi-quantitative RT-PCR. The MT content in gastric and hepatic tissues was determined by Cd/hemoglobin affinity assay. The lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were estimated by use of thiobarbituric acid reactive species and ultraviolet spectrophotometry. RESULTS: WIR stress induced severe gastric mucosal lesions in rats. Compared with control rats, stressed rats had increased lipid peroxide content in serum and stomach and liver tissues. MDA content was increased by 34%, 21% and 29% and CD level by 270%, 83% and 28%, respectively. MT content in the stomach and liver was increased by 0.74- and 1.8-fold, and the MT-mRNA level in the stomach was increased by 26%. Pretreatment with ZnSO4 prevented gastric lesion development (the UI was 87% lower than that without pretreatment), and the MDA and CD content in serum and tissues was lower. The MT content in the liver was double in rats that were not pretreated, and the MT mRNA level in the stomach was 35% higher. MT administration 1 h before the WIR stress prevented gastric lesion development (the UI decreased by 47% compared with that in rats not pretreated), and the MDA and CD content in serum and tissues was significantly lower. CONCLUSION: In WIR-stressed rats, the MT level was increased in serum and in stomach and liver tissues. Pre-administration of exogenous MT or pre-induction of endogenous MT can protect the gastric mucosa against stress-induced ulcers and inhibits the formation of stressinduced lipid peroxide. MT could have a gastroprotective effect and might be a new interventive and therapeutic target in stress-induced gastric ulcers.展开更多
AIM:Taurine has been shown to be an effective scavenger of hypochlorous acid (HOCI).The role of HOCI is well established in tissue damage associated with inflammation and injury. In the present study, the effect of HO...AIM:Taurine has been shown to be an effective scavenger of hypochlorous acid (HOCI).The role of HOCI is well established in tissue damage associated with inflammation and injury. In the present study, the effect of HOCl on nuclear nucleoside triphosphatase of hepatocytes and the ability of taurine to prevent this effect were investigated.METHODS:Isolated hepatic nuclei from rat liver were exposed to HOCl with or without taurine. The NTPase activity on nuclear envelope was assayed using ATP and GTP as substrates, respectively.RESULTS:The first series of experiments evaluated the toxicity of HOCl and the efficacy of taurine to protect NTPase.HOCI at 10^-9-5×10^-6 mol/L reduced nuclear NTPase activities in a concentration dependent manner (ATP and GTP as substrates) (P<0.01). HOCl at 10^-6mol/L reduced the NTPase activity by 65% (ATP as substrate) and 76% (GTP assubstrate). Taurine (10^-7 to 10^-4mol/L) was tested forprotection against HOCl at 10^-6mol/L and the nuclei treated with 5×10^-4mol/L taurine exhibited only 20% and 12% reduction in NTPase activities compared to untreated controls. A second study was performed comparing taurine to glutathione (GSH). GSH and HOCl at 10^-6mol/L exhibited 46% and 67.4% reduction in NTPase activities compared with control. GSH (10^-4mol/L) which was incubated with the nuclei and HOCI still exhibited 44.2% and 44.8% reduction in NTPase activities of untreated control. Taurine with HOCl only exhibited 15.2% and 17.1% reduction in NTPase activities, which provided more powerful protection against HOCI than GSH. The third experiment was undertaken to evaluate the specificity of taurine against HOCl. Incubation of rat hepatic nuclei with Fe^3+/H2O2 (1mmol/L vs 5μmol/L) resulted in a decrease in nuclear NTPase activities (P<0.01).When hepatic nuclei were incubated with Tau (10^-4mol/L) and Fe^3+/H2O2 (1mmol/L vs 5μmol/L), nuclear NTPase activities were only slightly increased as compared with that of incubation with Fe^3+/H2O2 alone. However, GSH failed to alter the NTPase activities induced by Fe^3+/H2O2.CONCLUSION:The present findings indicate that HOCl can act as an inhibitor of nuclear NTPase. Taurine can antagonistically reduce the toxicity of HOCI to NTPase.展开更多
Although it is recognized that im idazoline receptors play an im portant role in the central regulation of cardio- vascular activities,little is known about their role in the caudal ventrolateral m edulla.In m ale Spr...Although it is recognized that im idazoline receptors play an im portant role in the central regulation of cardio- vascular activities,little is known about their role in the caudal ventrolateral m edulla.In m ale Sprague- Dawley rats anes- thetized with urethane,we used antagonists of I1 - imidazoline receptor orα2 - adrenoceptor to assess the function of these recep- tors in the caudal ventrolateral m edulla in controlling the cardiovascular effects of clonidine.U nilateral microinjection of cloni- dine(6 nmol/ 5 0 nl) into the caudal ventrolateral m edulla significantly(P<0 .0 1 ) increased blood pressure and the discharge of the rostral ventrolateral medulla presym pathetic neurons,while heart rate remained unchanged.Microinjection of yohim - bine(a selectiveα2 - adrenoceptor antagonist,5 0 0 pm ol/ 5 0 nl) into the caudal ventrolateral medulla did notm odify blood pres- sure,heart rate,or the discharge of the rostral ventrolateral m edulla presym pathetic neurons,and failed to attenuate the local caudal ventrolateral m edulla clonidine- induced blood pressure elevation.However,unilateral microinjection of idazoxan (a mixed antagonist of imidazoline receptor andα2 - adrenoceptor,2 nmol/ 5 0 nl) into the caudal ventrolateral medulla signifi- cantly(P<0 .0 1 ) decreased m ean arterial pressure,heartrate,and the discharge of the rostral ventrolateral medulla presym - pathetic neurons,and completely abolished the pressor effect of clonidine.In addition,bilateral microinjection of idazoxan(4 nmol in1 0 0 nl for each side) into the caudal ventrolateral medulla effectively (P<0 .0 1 ) blocked the depressor effects of clonidine administered intravenously(5 and5 0 μg/ kg) .These results confirm that I1 - imidazoline receptors within the caudal ventrolateral medulla are involved inmaintaining the tonic cardiovascular activities and in the pressor effect of clonidine in the caudal ventrolateral medulla.In addition,itseem s that the caudal ventrolateral medulla plays an im portant role in the antihy- pertensive effects of systemically administered clonidine in展开更多
AIM: Previous work done by Al-Chaer' s lab has shown that colon irritation (CI) in neonates can lead to chronic visceral hypersensitivity in adult rats, with characteristics of visceral allodynia and hyperalgesia,...AIM: Previous work done by Al-Chaer' s lab has shown that colon irritation (CI) in neonates can lead to chronic visceral hypersensitivity in adult rats, with characteristics of visceral allodynia and hyperalgesia, associated with central neuronal sensitization in the absence of identifiable peripheral pathology (Al-Chaer et al. 2000) . The pathogenesis展开更多
AIM. To observe apoptosis of the neurocytes and the expression of BCL-2 and BAX proteins after focal cerebral ischemia-reperfusion injury (CIRI) in brain tissue of rats and the protective effects of rofecoxib. METHODS...AIM. To observe apoptosis of the neurocytes and the expression of BCL-2 and BAX proteins after focal cerebral ischemia-reperfusion injury (CIRI) in brain tissue of rats and the protective effects of rofecoxib. METHODS: The model of local CIRI was induced by reversible middle cerebral artery occlusion ( MCAO with inserting a thread through internal展开更多
基金The study was supported by grants from National Natural Science Foundation of Chinathe Science and Technology committee of Shanghai Municipality(02JC14038).
文摘Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion.Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins,Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion,enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group.Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion,expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl-2/Bax, especially in membrane fraction.
基金Supported by the NatiOnal Natural Science Foundation of China,No.30170419
文摘AIM: To explore the pathophysiological significance of delayed type hypersensitivity (DTH) reaction in mouse gastrointestinal tract induced by an allergen 2,4-dinitrochlorobenzene (DNCB).METHODS: BALB/c mice were randomly divided into control and DTH1-6 groups. After sensitized by DNCB smeared on the abdominal skin, the mice were challenged with DNCB by gavage or enema. The weight, stool viscosity and hematochezia were observed and accumulated as disease active index (DAI) score; the gastrointestinal motility was represented by active charcoal propulsion rate;the colon pathological score was achieved by macropathology and HE staining of section prepared for microscopy; and the leukocyte migration inhibitory factor (1MIF) activity was determined by indirect capillary assay of the absorbance (A) of migrated leukocytes.RESULTS: Active charcoal propulsion rates of small intestine in the DNCB gavages groups were significantly higher than that in the control group (P<0.01). The DAI scores and pathological score in DNCB enema groups were also higher than that in the control group (P<0.05), and there were significant rises in LMIF activity in DNCB enemagroups as compared with control groups (P<0.01).CONCLUSION: Mouse gastrointestinal DTH reaction could be induced by DNCB, which might facilitate the mechanism underlying the ulcerative colitis.
基金Supported by the State Major Basic Research Development Program of the People's Republic of China, No. 2003CCA041
文摘AIM: To illustrate the pathophysiological role of metallothionein (MT) in gastric ulcer induced by stress. METHODS: Wistar rats underwent water-immersionrestraint (WIR) stress, ZnSO4 (an MT inducer) treatment, WIR+ZnSO4 or WIR+MT, and the ulcer index (UI) was estimated in excised stomach and liver tissues. The mRNA level of gastric MT was determined by semi-quantitative RT-PCR. The MT content in gastric and hepatic tissues was determined by Cd/hemoglobin affinity assay. The lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were estimated by use of thiobarbituric acid reactive species and ultraviolet spectrophotometry. RESULTS: WIR stress induced severe gastric mucosal lesions in rats. Compared with control rats, stressed rats had increased lipid peroxide content in serum and stomach and liver tissues. MDA content was increased by 34%, 21% and 29% and CD level by 270%, 83% and 28%, respectively. MT content in the stomach and liver was increased by 0.74- and 1.8-fold, and the MT-mRNA level in the stomach was increased by 26%. Pretreatment with ZnSO4 prevented gastric lesion development (the UI was 87% lower than that without pretreatment), and the MDA and CD content in serum and tissues was lower. The MT content in the liver was double in rats that were not pretreated, and the MT mRNA level in the stomach was 35% higher. MT administration 1 h before the WIR stress prevented gastric lesion development (the UI decreased by 47% compared with that in rats not pretreated), and the MDA and CD content in serum and tissues was significantly lower. CONCLUSION: In WIR-stressed rats, the MT level was increased in serum and in stomach and liver tissues. Pre-administration of exogenous MT or pre-induction of endogenous MT can protect the gastric mucosa against stress-induced ulcers and inhibits the formation of stressinduced lipid peroxide. MT could have a gastroprotective effect and might be a new interventive and therapeutic target in stress-induced gastric ulcers.
基金Supported by the Major State Basic Research Development Program of People's Republic of China,No.G2000056905 and the National Natural Science Foundation of China,No.30070308
文摘AIM:Taurine has been shown to be an effective scavenger of hypochlorous acid (HOCI).The role of HOCI is well established in tissue damage associated with inflammation and injury. In the present study, the effect of HOCl on nuclear nucleoside triphosphatase of hepatocytes and the ability of taurine to prevent this effect were investigated.METHODS:Isolated hepatic nuclei from rat liver were exposed to HOCl with or without taurine. The NTPase activity on nuclear envelope was assayed using ATP and GTP as substrates, respectively.RESULTS:The first series of experiments evaluated the toxicity of HOCl and the efficacy of taurine to protect NTPase.HOCI at 10^-9-5×10^-6 mol/L reduced nuclear NTPase activities in a concentration dependent manner (ATP and GTP as substrates) (P<0.01). HOCl at 10^-6mol/L reduced the NTPase activity by 65% (ATP as substrate) and 76% (GTP assubstrate). Taurine (10^-7 to 10^-4mol/L) was tested forprotection against HOCl at 10^-6mol/L and the nuclei treated with 5×10^-4mol/L taurine exhibited only 20% and 12% reduction in NTPase activities compared to untreated controls. A second study was performed comparing taurine to glutathione (GSH). GSH and HOCl at 10^-6mol/L exhibited 46% and 67.4% reduction in NTPase activities compared with control. GSH (10^-4mol/L) which was incubated with the nuclei and HOCI still exhibited 44.2% and 44.8% reduction in NTPase activities of untreated control. Taurine with HOCl only exhibited 15.2% and 17.1% reduction in NTPase activities, which provided more powerful protection against HOCI than GSH. The third experiment was undertaken to evaluate the specificity of taurine against HOCl. Incubation of rat hepatic nuclei with Fe^3+/H2O2 (1mmol/L vs 5μmol/L) resulted in a decrease in nuclear NTPase activities (P<0.01).When hepatic nuclei were incubated with Tau (10^-4mol/L) and Fe^3+/H2O2 (1mmol/L vs 5μmol/L), nuclear NTPase activities were only slightly increased as compared with that of incubation with Fe^3+/H2O2 alone. However, GSH failed to alter the NTPase activities induced by Fe^3+/H2O2.CONCLUSION:The present findings indicate that HOCl can act as an inhibitor of nuclear NTPase. Taurine can antagonistically reduce the toxicity of HOCI to NTPase.
文摘Although it is recognized that im idazoline receptors play an im portant role in the central regulation of cardio- vascular activities,little is known about their role in the caudal ventrolateral m edulla.In m ale Sprague- Dawley rats anes- thetized with urethane,we used antagonists of I1 - imidazoline receptor orα2 - adrenoceptor to assess the function of these recep- tors in the caudal ventrolateral m edulla in controlling the cardiovascular effects of clonidine.U nilateral microinjection of cloni- dine(6 nmol/ 5 0 nl) into the caudal ventrolateral m edulla significantly(P<0 .0 1 ) increased blood pressure and the discharge of the rostral ventrolateral medulla presym pathetic neurons,while heart rate remained unchanged.Microinjection of yohim - bine(a selectiveα2 - adrenoceptor antagonist,5 0 0 pm ol/ 5 0 nl) into the caudal ventrolateral medulla did notm odify blood pres- sure,heart rate,or the discharge of the rostral ventrolateral m edulla presym pathetic neurons,and failed to attenuate the local caudal ventrolateral m edulla clonidine- induced blood pressure elevation.However,unilateral microinjection of idazoxan (a mixed antagonist of imidazoline receptor andα2 - adrenoceptor,2 nmol/ 5 0 nl) into the caudal ventrolateral medulla signifi- cantly(P<0 .0 1 ) decreased m ean arterial pressure,heartrate,and the discharge of the rostral ventrolateral medulla presym - pathetic neurons,and completely abolished the pressor effect of clonidine.In addition,bilateral microinjection of idazoxan(4 nmol in1 0 0 nl for each side) into the caudal ventrolateral medulla effectively (P<0 .0 1 ) blocked the depressor effects of clonidine administered intravenously(5 and5 0 μg/ kg) .These results confirm that I1 - imidazoline receptors within the caudal ventrolateral medulla are involved inmaintaining the tonic cardiovascular activities and in the pressor effect of clonidine in the caudal ventrolateral medulla.In addition,itseem s that the caudal ventrolateral medulla plays an im portant role in the antihy- pertensive effects of systemically administered clonidine in
文摘AIM: Previous work done by Al-Chaer' s lab has shown that colon irritation (CI) in neonates can lead to chronic visceral hypersensitivity in adult rats, with characteristics of visceral allodynia and hyperalgesia, associated with central neuronal sensitization in the absence of identifiable peripheral pathology (Al-Chaer et al. 2000) . The pathogenesis
文摘AIM. To observe apoptosis of the neurocytes and the expression of BCL-2 and BAX proteins after focal cerebral ischemia-reperfusion injury (CIRI) in brain tissue of rats and the protective effects of rofecoxib. METHODS: The model of local CIRI was induced by reversible middle cerebral artery occlusion ( MCAO with inserting a thread through internal
