Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and determining whether nitric oxide and neurogenic pathway play an important role in the mechanism o...Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and determining whether nitric oxide and neurogenic pathway play an important role in the mechanism of acute remote ischemic preconditioning （IPC）.Methods Forty Wistar rats were randomly divided into four experimental groups. In Group I , the rats underwent 30-minute occlusion of the left anterior descending coronary artery, and 120-minute reperfusion. In Group PL, the rats underwent four cycles of 5-minute occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group I. In Group PL-N and Group PL-,, we administered L-nitro-arginine methyl ester （L-NAME） 10 mg/kg or hexamethonium chloride 20 mg,/kg intravenously, 10 minutes before IPC. Infarct size as a percentage of the area at risk was determined by triphenyhetrazolium chloride staining.Results There were no statistically significant differences in mean arterial pressure and heart rate among these groups at any time point during the experiment （ P〉0. 05 ）. The myocardial infarct size （IS） was decreased significantly in Group PL and Group PL-U compared with Group I , and the IS/AAR was 34. 5%± 7.6%, 35.9%±8.6% and58.5%±8.5%, respectively （P〈0.05）. The IS/AAR was 49.1%±6.5% in Group PEN, and there was no significant difference compared with Group I （P〉0. 05 ）.Conclusions Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. Nitric oxide plays an important role in the mechanism of acute remote IPC, in which the neurogenic pathway is not involved.展开更多
目的探讨GABA及其受体在心肌梗死缺血再灌注损伤过程中的心肌保护机制。方法取自SD大鼠的原代心室肌细胞,根据不同干预分为6组:空白对照组(BC组)无任何干预措施;空白模型组(BM组)模拟缺血再灌注模型,缺糖缺氧培养6 h后,恢复正常含糖及...目的探讨GABA及其受体在心肌梗死缺血再灌注损伤过程中的心肌保护机制。方法取自SD大鼠的原代心室肌细胞,根据不同干预分为6组:空白对照组(BC组)无任何干预措施;空白模型组(BM组)模拟缺血再灌注模型,缺糖缺氧培养6 h后,恢复正常含糖及氧浓度培养3 h;干预组包括:在缺糖缺氧及复糖复氧开始时给予GABA 100μmol/L(GBAB组)、GABABR激动剂巴氯芬100μmol/L(Baclofen组)、TLR4拮抗剂E5564 100μmol/L(E5564组)以及GABABR拮抗剂CGP35348 100μmol/L(CGP35348组)。MTT方法检测心肌细胞活力,RT-qPCR方法检测心肌细胞GABABR及TLR4基因表达。ELISA法检测上清液TNF-α、CKMB。结果缺血再灌注损伤前后,心肌细胞活力严重受损,重要保护因子GABABR基因表达显著下调(0.72 vs 0.23,P <0.001),而关键促炎因子TLR4基因表达显著升高(1.40 vs 1.60,P <0.05),CKMB、TNF-α均显著升高(4.70±3.08 vs 34.10±13.75,25.50±9.78vs 68.75±12.97,P <0.001)。与BM组比较,Baclofen组GABABR、TLR4基因表达变化均无统计学差异,其炎性指标CKMB、TNF-α均显著下降(19.46±8.43 vs 34.10±13.75,47.31±14.79 vs 68.75±12.97,P <0.01);CGP35348组因失去GABABR保护,其结果与BM组基本一致。结论 GABA及其受体通过抑制促炎细胞因子来减轻炎症反应,从而在心肌梗死缺血再灌注损伤过程中起到心肌保护作用。TLR4通路在该心肌保护机制中可能发挥重要调节作用。展开更多
基金This study was supported by a grant from the Natural ScienceFoundation of Liaoning Education Committee (No.2004D193).
文摘Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and determining whether nitric oxide and neurogenic pathway play an important role in the mechanism of acute remote ischemic preconditioning （IPC）.Methods Forty Wistar rats were randomly divided into four experimental groups. In Group I , the rats underwent 30-minute occlusion of the left anterior descending coronary artery, and 120-minute reperfusion. In Group PL, the rats underwent four cycles of 5-minute occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group I. In Group PL-N and Group PL-,, we administered L-nitro-arginine methyl ester （L-NAME） 10 mg/kg or hexamethonium chloride 20 mg,/kg intravenously, 10 minutes before IPC. Infarct size as a percentage of the area at risk was determined by triphenyhetrazolium chloride staining.Results There were no statistically significant differences in mean arterial pressure and heart rate among these groups at any time point during the experiment （ P〉0. 05 ）. The myocardial infarct size （IS） was decreased significantly in Group PL and Group PL-U compared with Group I , and the IS/AAR was 34. 5%± 7.6%, 35.9%±8.6% and58.5%±8.5%, respectively （P〈0.05）. The IS/AAR was 49.1%±6.5% in Group PEN, and there was no significant difference compared with Group I （P〉0. 05 ）.Conclusions Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. Nitric oxide plays an important role in the mechanism of acute remote IPC, in which the neurogenic pathway is not involved.
文摘目的探讨GABA及其受体在心肌梗死缺血再灌注损伤过程中的心肌保护机制。方法取自SD大鼠的原代心室肌细胞,根据不同干预分为6组:空白对照组(BC组)无任何干预措施;空白模型组(BM组)模拟缺血再灌注模型,缺糖缺氧培养6 h后,恢复正常含糖及氧浓度培养3 h;干预组包括:在缺糖缺氧及复糖复氧开始时给予GABA 100μmol/L(GBAB组)、GABABR激动剂巴氯芬100μmol/L(Baclofen组)、TLR4拮抗剂E5564 100μmol/L(E5564组)以及GABABR拮抗剂CGP35348 100μmol/L(CGP35348组)。MTT方法检测心肌细胞活力,RT-qPCR方法检测心肌细胞GABABR及TLR4基因表达。ELISA法检测上清液TNF-α、CKMB。结果缺血再灌注损伤前后,心肌细胞活力严重受损,重要保护因子GABABR基因表达显著下调(0.72 vs 0.23,P <0.001),而关键促炎因子TLR4基因表达显著升高(1.40 vs 1.60,P <0.05),CKMB、TNF-α均显著升高(4.70±3.08 vs 34.10±13.75,25.50±9.78vs 68.75±12.97,P <0.001)。与BM组比较,Baclofen组GABABR、TLR4基因表达变化均无统计学差异,其炎性指标CKMB、TNF-α均显著下降(19.46±8.43 vs 34.10±13.75,47.31±14.79 vs 68.75±12.97,P <0.01);CGP35348组因失去GABABR保护,其结果与BM组基本一致。结论 GABA及其受体通过抑制促炎细胞因子来减轻炎症反应,从而在心肌梗死缺血再灌注损伤过程中起到心肌保护作用。TLR4通路在该心肌保护机制中可能发挥重要调节作用。
