AIM: To explore the effect of sulfated cholecystokinin octapeptide (sCCK-8) on cardiac functions and its receptor mechanism in endotoxic shock (ES) rats. METHODS: The changes of the mean arterial pressure (MAP), heart...AIM: To explore the effect of sulfated cholecystokinin octapeptide (sCCK-8) on cardiac functions and its receptor mechanism in endotoxic shock (ES) rats. METHODS: The changes of the mean arterial pressure (MAP), heart rate (HR), the left ventricular pressure (LVP) and the maximal/minimum rate of LVP (±LVdp/dt max) were measured by using physiological record instrument in eight groups of rats. The expression of cholecystokinin-A receptor (CCK-AR) and cholecystokinin-B receptor (CCK-BR) mRNA of myocardium in ES rats was examined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: (1) Low doses of sCCK-8 (0.4 μg/kg) caused tachycardia (441±27, normal control 391±22 s/min) and slight increase in MAP, LVP and ±LVdp/dtmax (16.96±1.79, 18.21±1.69 and +768.85±31.28/-565.04±27.71 kPa, respectively, all P<0.01), while medium doses (4.0 μg/kg) and high doses of sCCK-8 (40 μg/kg) elicited bradycardia and marked increase in MAP, LVP and ±LVdp/dtmax (17.29±1.63, 19.46±2.57 and +831.46±22.57/-606.08 ±31.32; 17.46±1.08, 19.83±2.91 and +914.52±35.95/ -639.15±30.23 kPa, respectively, all P<0.01). Proglumide (1.0 mg/kg), a nonselective antagonist of CCK-receptor (CCK-R), significantly inhibited the pressor effects of sCCK-8 (15.96±1.38, 17.36±0.66 and +748.18±19.29/-512.12±14.39 kPa, respectively, all P<0.01), whilst reversing the bradycardiac responses. (2) High doses of LPS (8 mg/kg) elicited marked decrease in MAP, LVP and ±LVdp/dtmax. (7.16±0.59, 7.6±0.68 and +298.01±25.52/ -166.96±19.25 kPa, respectively, all P<0.01). Pretreatment with sCCK-8 (40 μg/kg) could reverse the decline of cardiac functions (10.71±0.45, 11.7±1.26 and +446.04±67.18/ -347.90±36.98 kPa, respectively, all P<0.01), while proglumide could cause further decline of cardiac function in ES rats (4.71±0.67, 5.58±1.25 and +226.48±15.84/ -142.83±20.23 kPa, respectively, all P<0.01). (3) CCK-A/BR mRNAs were expressed in myocardium of control rats. Gene expression of CCK-AR and CCK-BR significantly increased in myocardium of ES rats. The increase of CCK-AR mRNA induced by LPS began at 0.5 h, peaked at 2 h, kept a high level at 6 h and declined at 12 h, respectively. Similar to CCK-AR mRNA, the expression of CCK-BR mRNA peaked at 2 h and kept a high level at 6 h, but it did not change at the first 0.5 h and was stable at a high level at 12 h. CONCLUSION: The above results indicate that endogenous and exogenous sCCK-8 may significantly improve cardiac function and intractable hypotension of ES rats, which was likely related to high expression of CCK-A/BR in myocardium induced by LPS.展开更多
In present work,EEG and BP were used as the indexes to observe the relationbetween the change of EEG and the change of BP in the endotoxic shocked rats。At maintainingshock for 1 hr,dysrhythmia of EEG appeared in 38/4...In present work,EEG and BP were used as the indexes to observe the relationbetween the change of EEG and the change of BP in the endotoxic shocked rats。At maintainingshock for 1 hr,dysrhythmia of EEG appeared in 38/46 cases.Simultaneously,there was a markeddrop in Bp,P【0.05.Following the shocked time prolonged,dysrhythmia was getting severe。AfterEA”Rengzhong"(n=14)or“Zusanli”(n=12),BP was significantly increased(P【0.05),anddysrhythmia of EEG showed clear improvement in most of the rats。There was a close relation be-tween the changes of EEG and BP,the change of EEG had a direct bearing on the change of BP.展开更多
The CD11a/CD18 monoclonal antibody was injected into rabbits with endotoxic shock in order to observe the effect of the antibody on microcirculation. The resuh showed that the injection of CD11a/CD18 monoclonal antibo...The CD11a/CD18 monoclonal antibody was injected into rabbits with endotoxic shock in order to observe the effect of the antibody on microcirculation. The resuh showed that the injection of CD11a/CD18 monoclonal antibody could obviously reduce the number of leukocytes adhered on the venule wall, increase the blood velocity and attenuate the falling of mean arterial pressure in the shock rabbits, which indicates that CD11a/CD18 takes part in the pathogenesis of leukocytes adherence in endotoxic shock. Blocking CD11a/CD18 can improve microcirculation to a certain extent.展开更多
Objective To investigate the effect of methylene blue (MB) on the blood pressure and cGMP ofendotoxic shock. Methods An experiment was performed on 16 New Zealand rabbits suffering from endotoxicshock, in which 8 were...Objective To investigate the effect of methylene blue (MB) on the blood pressure and cGMP ofendotoxic shock. Methods An experiment was performed on 16 New Zealand rabbits suffering from endotoxicshock, in which 8 were distributed to the trial group (MB infusion) and another 8 to the control group (normalsaline). The mean arterial pressure (MAP), plasma cyclic monophosphate guanylate (cGMP), and arterialnatriuretic factor (ANF) in the two groups were observed. Results in the trial group MB infusion elevated MAP(P<0.01), decreased cGMP (P<0.01) and did not change the level of ANF. In the control group, normal salineinfusion did not alter MAP, plasma cGMP and ANF level. In addition, the MAP of the trial group was foundsignificantly higher than that of the control group (P<0.01) and the plasma cGMP of the trial group significantlylower than that of the control group (P<0.01). Conclusion These data suggest that the elevation of plasmacGMP is related to hypotension and MB in vivo can effectively inhibit soluable guanylate Cyclase, thus decreaseplasma cGMP level and increase MAP of rabbits with endotoxic shock. This indicates that MB can be used as adrug for the treatment of endotoxic shock.展开更多
objective: To investigate the protective effects of bactericidal/permeability-increa protein (BPIP) on rats after endotoxic shock as to provide more experimental evidence for studies on its clinical use. Methods:E. co...objective: To investigate the protective effects of bactericidal/permeability-increa protein (BPIP) on rats after endotoxic shock as to provide more experimental evidence for studies on its clinical use. Methods:E. coli 026:B6 LPS was injected at a dosage of 12. 5 mg/kg through the artery to reproduce endo toxic shock. BPIP at a dosage of 5 mg/kg (BPIP-treated group) or equal volume of normal saline (control group) were injected immediately after the injection of LPS. Results: ①Survival time of the shocked animals was prolonged and the 24 h survival rate was also significantly increased in BPIP-treated group as compared with the control group. ②The mean arterial pressure, left intraventricular systolic pressure, isovolemic ven tricular pressure and ±dp/dtmax. were significantly higher in BPIP-treated group than in control group. ③ Plasma levels of glutamic-pyruvic transaminase and urea nitrogen were markedly higher but those of endotox in and TNFα were lower in BPIP-treated group than in control group. Conclusion: BPIP can exert significant protective effects on cardiac, hepatic and renal functions in rats after endotoxic shock, indicating that BPIP might be a good choice in treatment of sepsis/septic shock.展开更多
The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits we...The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits were randomized into 4 groups as follows : The normal control (NC) group consisted of 12 rabbits with sham injection . the endotoxic shork (ES) group of 31 rabbits, the chloquine pretreated (CQ) group of 16 rabbits receiving 3 mg/kg of chlorqouine and the dexamethasone-pretreated (DM) group of 10 rabbits receiving 5 mg/kg of dexamethasone. Blood was sampled before and 5 and 30 min, 1 ,3, 5 and 8 h after the administration of endotoxin for the determination of PLA2, platelet activating factor (PAF) , TXB2 and 6-keto-PGF1α. In addrtion, changes of mean arterial pressure (MAP) and respiratory rate (RR) were also carefully recorded. It was found that the activities of PLA2 and PAF and the levels of TXB2 and 6-keto-PGF1α. were significantly increased after the infusion of endotoxin. CQ and DM markedly suppressed the activities of PLA2 and PAF. The inhibition of CQ on TXB2 and 6-keto-PGF1α was greater than that of DM. Besides, CQ and DM could increase the survival rate of the animals from 48% to 75% (CQ group) and 70% (DM group). These findings suggest that PLA2 inhibitors such as CQ and DM can significantly attenuate the formation of shock mediators such as PLA2, PAF, TXB2 and 6-keto-PGF1α, and so improve the prognosis of the victims of endotoxic shock.展开更多
To investigate the effect of Flunixin meglumine- a NSAID;alone and in combination with hypertonic saline on endotoxemic buffalo calves, two groups of five apparently healthy male buffalo calves aged be-tween 6-8 month...To investigate the effect of Flunixin meglumine- a NSAID;alone and in combination with hypertonic saline on endotoxemic buffalo calves, two groups of five apparently healthy male buffalo calves aged be-tween 6-8 months were subjected to I.V. infusion of E.coli endotoxin at the rate of 5μg/kg BW per hour for 3 hours. A highly significant (P < 0.01) fall in mean systolic,diastolic, pulse, mean arterial pressure (M.A.P), central venous pressure (C.V.P) and haemo-globin was observed till the end of endotoxin infusion while respiratory rate was significantly elevated along with a non-significant alteration in rectal tem-perature and hematocrit during the infusion of en-dotoxin. Immediately at the end of endotoxin infusion, flunixin meglumine at the rate of 1.1 mg/kg B.W was infused i.v. in group-I animals and group-II animals were infused with hypertonic saline solution (H.S.S.) at the rate of 4 ml/Kg BW as one time infusion fol-lowed by flunixin meglumine at the rate of 1.1 mg/kg B.W which resulted in increase of various parameters either to normal or very close to normal value while the rectal temperature and haematocrit decreased non-significantly throughout the observation period of 7 hours. No improvement in Hb and respiration was observed consequent to FM administration. Both treatments successfully raised systolic, diastolic, pulse pressure, C.V.P & M.A.P to normal pre-infusion val-ues. From the results of the present investigation, it can be concluded that i.v. infusion of FM alone and in combination with hypertonic saline solution in en-dotoxemic buffalo calves effectively restores the various hemodynamic parameters close to normal pre-infusion values and it can be used as immediate resuscitation measure to provide the clinician valu-able time to plan further long term treatment.展开更多
Suppressor of cytokine signaling 3 （SOCS3） was reported as a feedback inhibitor of cytokine receptor signaling by inhibiting the JAK-STAT signal transduction pathway. We sought to test the anti-endotoxic septic shoc...Suppressor of cytokine signaling 3 （SOCS3） was reported as a feedback inhibitor of cytokine receptor signaling by inhibiting the JAK-STAT signal transduction pathway. We sought to test the anti-endotoxic septic shock effect of liposome mediated gene delivery of SOCS3 in a lethal endotoxic shock mouse model. BALB/c mice were injected intraperitoneally with 200μg pcDNA3.1-SOCS3 cationic liposomes, while pcDNA3.1-IL-10 and empty vector as positive and negative control respectively. Forty-eight hours after gene delivery, mice were challenged with 4 μg of E.coli 0127：B8 LPS and 18 mg D-GaIN administered i.p. 90 min later, serum TNF-α level was determined. Survival over the next 48 h was evaluated. Peritoneal macrophages from survival mice were stimulated in vitro with 1 μg/ml LPS for 18 h, and the supernatants were harvested for determination of the amount of TNF-α. We found that gene delivery of SOCS3 significantly increase the mouse survival rate from 27.8 ± 9.6% of control group to 61.1 ± 9.6% （p 〈 0.01）. In comparison with control group （218 ± 13 pg/ml） and sham delivery group （219 ± 22 pg/ml）, gene delivery of SOCS3 reduced the level of serum TNF-α （68 ± 9 pg/ml） significantly （p 〈 0.01）. Furthermore, gene delivery of SOCS3 displayed the capacity of prevention of tolerance of peritoneal macrophages to LPS. These findings suggest that gene delivery of SOCS3 mediated by liposome is a promising approach for endotoxic septic shock treatment. Cellular ＆ Molecular Immunology.展开更多
Summary: To investigate the role of NF-κB in endotoxic shock in rats, the model of endotoxin-shock rats was induced by intravenous infusion of lipopolysaccharide (LPS). 1 h, 2 h, 4 h and 6 h after LPS injection, the...Summary: To investigate the role of NF-κB in endotoxic shock in rats, the model of endotoxin-shock rats was induced by intravenous infusion of lipopolysaccharide (LPS). 1 h, 2 h, 4 h and 6 h after LPS injection, the activation of NF-κB in blood mononuclear cells and the content of TNF-α and IL-6 in plasma was detected by enzyme-linked immunoadsordent assay (ELISA). The level of mean arterial pressure (MAP) and the histopathological changes of lung and liver were also observed. The activation of NF-κB in mononuclear cells increased 1 h after LPS injection and reached its peak 2 h after the injection, and its level was higher than that of normal group. The level of TNF-α was increased 1 h after the infusion and peaked 2 h after the injection, and its level was higher than that of normal group after LPS infusion. The content of IL-6 increased gradually with time, the IL-6 level was higher than that of normal group after LPS injection. MAP was decreased gradually with time and its level was lower than that of normal group after LPS injection. Pathological examination showed that endotoxic shock could cause pulmonary alveolar hemorrhage, edema and infiltration of inflammatory cell in lung tissue and congestion, edema, capillary dilation and inflammatory cell infiltration in liver tissue. It is concluded that NF-κB can up-regulate the expression of TNF-α and IL-6 in plasma and play an important role in endotoxin-induced shock in rats.展开更多
基金Supported by the projects of Health Committee and Education Committee of Hebei Province, No. 2K002, and No. 200122
文摘AIM: To explore the effect of sulfated cholecystokinin octapeptide (sCCK-8) on cardiac functions and its receptor mechanism in endotoxic shock (ES) rats. METHODS: The changes of the mean arterial pressure (MAP), heart rate (HR), the left ventricular pressure (LVP) and the maximal/minimum rate of LVP (±LVdp/dt max) were measured by using physiological record instrument in eight groups of rats. The expression of cholecystokinin-A receptor (CCK-AR) and cholecystokinin-B receptor (CCK-BR) mRNA of myocardium in ES rats was examined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: (1) Low doses of sCCK-8 (0.4 μg/kg) caused tachycardia (441±27, normal control 391±22 s/min) and slight increase in MAP, LVP and ±LVdp/dtmax (16.96±1.79, 18.21±1.69 and +768.85±31.28/-565.04±27.71 kPa, respectively, all P<0.01), while medium doses (4.0 μg/kg) and high doses of sCCK-8 (40 μg/kg) elicited bradycardia and marked increase in MAP, LVP and ±LVdp/dtmax (17.29±1.63, 19.46±2.57 and +831.46±22.57/-606.08 ±31.32; 17.46±1.08, 19.83±2.91 and +914.52±35.95/ -639.15±30.23 kPa, respectively, all P<0.01). Proglumide (1.0 mg/kg), a nonselective antagonist of CCK-receptor (CCK-R), significantly inhibited the pressor effects of sCCK-8 (15.96±1.38, 17.36±0.66 and +748.18±19.29/-512.12±14.39 kPa, respectively, all P<0.01), whilst reversing the bradycardiac responses. (2) High doses of LPS (8 mg/kg) elicited marked decrease in MAP, LVP and ±LVdp/dtmax. (7.16±0.59, 7.6±0.68 and +298.01±25.52/ -166.96±19.25 kPa, respectively, all P<0.01). Pretreatment with sCCK-8 (40 μg/kg) could reverse the decline of cardiac functions (10.71±0.45, 11.7±1.26 and +446.04±67.18/ -347.90±36.98 kPa, respectively, all P<0.01), while proglumide could cause further decline of cardiac function in ES rats (4.71±0.67, 5.58±1.25 and +226.48±15.84/ -142.83±20.23 kPa, respectively, all P<0.01). (3) CCK-A/BR mRNAs were expressed in myocardium of control rats. Gene expression of CCK-AR and CCK-BR significantly increased in myocardium of ES rats. The increase of CCK-AR mRNA induced by LPS began at 0.5 h, peaked at 2 h, kept a high level at 6 h and declined at 12 h, respectively. Similar to CCK-AR mRNA, the expression of CCK-BR mRNA peaked at 2 h and kept a high level at 6 h, but it did not change at the first 0.5 h and was stable at a high level at 12 h. CONCLUSION: The above results indicate that endogenous and exogenous sCCK-8 may significantly improve cardiac function and intractable hypotension of ES rats, which was likely related to high expression of CCK-A/BR in myocardium induced by LPS.
基金The Project Supported by National Natural Science Foundation of China
文摘In present work,EEG and BP were used as the indexes to observe the relationbetween the change of EEG and the change of BP in the endotoxic shocked rats。At maintainingshock for 1 hr,dysrhythmia of EEG appeared in 38/46 cases.Simultaneously,there was a markeddrop in Bp,P【0.05.Following the shocked time prolonged,dysrhythmia was getting severe。AfterEA”Rengzhong"(n=14)or“Zusanli”(n=12),BP was significantly increased(P【0.05),anddysrhythmia of EEG showed clear improvement in most of the rats。There was a close relation be-tween the changes of EEG and BP,the change of EEG had a direct bearing on the change of BP.
文摘The CD11a/CD18 monoclonal antibody was injected into rabbits with endotoxic shock in order to observe the effect of the antibody on microcirculation. The resuh showed that the injection of CD11a/CD18 monoclonal antibody could obviously reduce the number of leukocytes adhered on the venule wall, increase the blood velocity and attenuate the falling of mean arterial pressure in the shock rabbits, which indicates that CD11a/CD18 takes part in the pathogenesis of leukocytes adherence in endotoxic shock. Blocking CD11a/CD18 can improve microcirculation to a certain extent.
文摘Objective To investigate the effect of methylene blue (MB) on the blood pressure and cGMP ofendotoxic shock. Methods An experiment was performed on 16 New Zealand rabbits suffering from endotoxicshock, in which 8 were distributed to the trial group (MB infusion) and another 8 to the control group (normalsaline). The mean arterial pressure (MAP), plasma cyclic monophosphate guanylate (cGMP), and arterialnatriuretic factor (ANF) in the two groups were observed. Results in the trial group MB infusion elevated MAP(P<0.01), decreased cGMP (P<0.01) and did not change the level of ANF. In the control group, normal salineinfusion did not alter MAP, plasma cGMP and ANF level. In addition, the MAP of the trial group was foundsignificantly higher than that of the control group (P<0.01) and the plasma cGMP of the trial group significantlylower than that of the control group (P<0.01). Conclusion These data suggest that the elevation of plasmacGMP is related to hypotension and MB in vivo can effectively inhibit soluable guanylate Cyclase, thus decreaseplasma cGMP level and increase MAP of rabbits with endotoxic shock. This indicates that MB can be used as adrug for the treatment of endotoxic shock.
文摘objective: To investigate the protective effects of bactericidal/permeability-increa protein (BPIP) on rats after endotoxic shock as to provide more experimental evidence for studies on its clinical use. Methods:E. coli 026:B6 LPS was injected at a dosage of 12. 5 mg/kg through the artery to reproduce endo toxic shock. BPIP at a dosage of 5 mg/kg (BPIP-treated group) or equal volume of normal saline (control group) were injected immediately after the injection of LPS. Results: ①Survival time of the shocked animals was prolonged and the 24 h survival rate was also significantly increased in BPIP-treated group as compared with the control group. ②The mean arterial pressure, left intraventricular systolic pressure, isovolemic ven tricular pressure and ±dp/dtmax. were significantly higher in BPIP-treated group than in control group. ③ Plasma levels of glutamic-pyruvic transaminase and urea nitrogen were markedly higher but those of endotox in and TNFα were lower in BPIP-treated group than in control group. Conclusion: BPIP can exert significant protective effects on cardiac, hepatic and renal functions in rats after endotoxic shock, indicating that BPIP might be a good choice in treatment of sepsis/septic shock.
文摘The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits were randomized into 4 groups as follows : The normal control (NC) group consisted of 12 rabbits with sham injection . the endotoxic shork (ES) group of 31 rabbits, the chloquine pretreated (CQ) group of 16 rabbits receiving 3 mg/kg of chlorqouine and the dexamethasone-pretreated (DM) group of 10 rabbits receiving 5 mg/kg of dexamethasone. Blood was sampled before and 5 and 30 min, 1 ,3, 5 and 8 h after the administration of endotoxin for the determination of PLA2, platelet activating factor (PAF) , TXB2 and 6-keto-PGF1α. In addrtion, changes of mean arterial pressure (MAP) and respiratory rate (RR) were also carefully recorded. It was found that the activities of PLA2 and PAF and the levels of TXB2 and 6-keto-PGF1α. were significantly increased after the infusion of endotoxin. CQ and DM markedly suppressed the activities of PLA2 and PAF. The inhibition of CQ on TXB2 and 6-keto-PGF1α was greater than that of DM. Besides, CQ and DM could increase the survival rate of the animals from 48% to 75% (CQ group) and 70% (DM group). These findings suggest that PLA2 inhibitors such as CQ and DM can significantly attenuate the formation of shock mediators such as PLA2, PAF, TXB2 and 6-keto-PGF1α, and so improve the prognosis of the victims of endotoxic shock.
文摘To investigate the effect of Flunixin meglumine- a NSAID;alone and in combination with hypertonic saline on endotoxemic buffalo calves, two groups of five apparently healthy male buffalo calves aged be-tween 6-8 months were subjected to I.V. infusion of E.coli endotoxin at the rate of 5μg/kg BW per hour for 3 hours. A highly significant (P < 0.01) fall in mean systolic,diastolic, pulse, mean arterial pressure (M.A.P), central venous pressure (C.V.P) and haemo-globin was observed till the end of endotoxin infusion while respiratory rate was significantly elevated along with a non-significant alteration in rectal tem-perature and hematocrit during the infusion of en-dotoxin. Immediately at the end of endotoxin infusion, flunixin meglumine at the rate of 1.1 mg/kg B.W was infused i.v. in group-I animals and group-II animals were infused with hypertonic saline solution (H.S.S.) at the rate of 4 ml/Kg BW as one time infusion fol-lowed by flunixin meglumine at the rate of 1.1 mg/kg B.W which resulted in increase of various parameters either to normal or very close to normal value while the rectal temperature and haematocrit decreased non-significantly throughout the observation period of 7 hours. No improvement in Hb and respiration was observed consequent to FM administration. Both treatments successfully raised systolic, diastolic, pulse pressure, C.V.P & M.A.P to normal pre-infusion val-ues. From the results of the present investigation, it can be concluded that i.v. infusion of FM alone and in combination with hypertonic saline solution in en-dotoxemic buffalo calves effectively restores the various hemodynamic parameters close to normal pre-infusion values and it can be used as immediate resuscitation measure to provide the clinician valu-able time to plan further long term treatment.
文摘Suppressor of cytokine signaling 3 （SOCS3） was reported as a feedback inhibitor of cytokine receptor signaling by inhibiting the JAK-STAT signal transduction pathway. We sought to test the anti-endotoxic septic shock effect of liposome mediated gene delivery of SOCS3 in a lethal endotoxic shock mouse model. BALB/c mice were injected intraperitoneally with 200μg pcDNA3.1-SOCS3 cationic liposomes, while pcDNA3.1-IL-10 and empty vector as positive and negative control respectively. Forty-eight hours after gene delivery, mice were challenged with 4 μg of E.coli 0127：B8 LPS and 18 mg D-GaIN administered i.p. 90 min later, serum TNF-α level was determined. Survival over the next 48 h was evaluated. Peritoneal macrophages from survival mice were stimulated in vitro with 1 μg/ml LPS for 18 h, and the supernatants were harvested for determination of the amount of TNF-α. We found that gene delivery of SOCS3 significantly increase the mouse survival rate from 27.8 ± 9.6% of control group to 61.1 ± 9.6% （p 〈 0.01）. In comparison with control group （218 ± 13 pg/ml） and sham delivery group （219 ± 22 pg/ml）, gene delivery of SOCS3 reduced the level of serum TNF-α （68 ± 9 pg/ml） significantly （p 〈 0.01）. Furthermore, gene delivery of SOCS3 displayed the capacity of prevention of tolerance of peritoneal macrophages to LPS. These findings suggest that gene delivery of SOCS3 mediated by liposome is a promising approach for endotoxic septic shock treatment. Cellular ＆ Molecular Immunology.
基金This project was supported by a grant from Hubei Province Science and Technology Foundation (2003AA301C51).
文摘Summary: To investigate the role of NF-κB in endotoxic shock in rats, the model of endotoxin-shock rats was induced by intravenous infusion of lipopolysaccharide (LPS). 1 h, 2 h, 4 h and 6 h after LPS injection, the activation of NF-κB in blood mononuclear cells and the content of TNF-α and IL-6 in plasma was detected by enzyme-linked immunoadsordent assay (ELISA). The level of mean arterial pressure (MAP) and the histopathological changes of lung and liver were also observed. The activation of NF-κB in mononuclear cells increased 1 h after LPS injection and reached its peak 2 h after the injection, and its level was higher than that of normal group. The level of TNF-α was increased 1 h after the infusion and peaked 2 h after the injection, and its level was higher than that of normal group after LPS infusion. The content of IL-6 increased gradually with time, the IL-6 level was higher than that of normal group after LPS injection. MAP was decreased gradually with time and its level was lower than that of normal group after LPS injection. Pathological examination showed that endotoxic shock could cause pulmonary alveolar hemorrhage, edema and infiltration of inflammatory cell in lung tissue and congestion, edema, capillary dilation and inflammatory cell infiltration in liver tissue. It is concluded that NF-κB can up-regulate the expression of TNF-α and IL-6 in plasma and play an important role in endotoxin-induced shock in rats.
