TG-6对大鼠心肌缺血再灌注损伤的保护作用及其机制研究

Protective effects of TG-6 on myocardial ischemia-reperfusion injury and its mechanism

目的:研究新化合物TG-6对大鼠心肌缺血再灌注(myocardial ischemia reperfusion,I/R)损伤的保护作用及其机制。方法:大鼠于I/R前5 min尾静脉注射药物,结扎大鼠左冠状动脉前降支缺血45 min,再灌注24 h后,测定大鼠心电图,心肌组织HE染色观察其病理学变化;测定血清中乳酸脱氢酶(lactate dehydrogenase,LDH)、肌酸激酶(creatine kinase,CK)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)等含量;检测血清中炎症因子,如肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin-6,IL-6)、白介素-1β(interleukin-1β,IL-1β)含量,Western blot测定TLR4、IκBα、NF-κB蛋白的表达。结果:与模型组相比,TG-6可以明显改善心电图S-T段的抬高,减轻心肌组织梗死面积和病理损伤,显著降低血清中LDH、CK、MDA、TNF-α、IL-6和IL-1β的含量,增加SOD活性。TG-6能减少心肌组织中TLR4、IκBα、NF-κB蛋白的表达。结论:TG-6对心肌缺血再灌注损伤具有保护作用,其机制可能与抗炎和抗氧化有关。

Objective：To investigate the effect of TG-6 on myocardial ischemia reperfusion injury in rats and the underlying mechanism. Methods：The drugs were administered by intravenous injection 5 min before ischemia reperfusion（I/R）injury. Myocardial ischemia reperfusion injury（MI/RI）model was treated by 45 min of left anterior descending（LAD）occlusion followed by 24 h of reperfusion. Measurement of rat electrocardiogram（ECG）,hematoxylin-eosin（HE）staining of cardiac tissue,serum lactate dehydrogenase（LDH）,creatine kinase（CK）,superoxide dismutase（SOD）and malondialdehyde（MDA）. Serum inflammatory cytokines,such as tumor necrosis factor-α（TNF-α）,interleukin-6（IL-6）and interleukin-1β（IL-1β）were measured by ELISA kits. The protein expression of TLR4,IκBα and NF-κB were measured by Western blot. Results：Compared with the I/R group,TG-6 decreased S-T elevation,reduced myocardial pathological lesions,significantly decreased serum LDH,CK,MDA,TNF-α,IL-6,IL-1β content,and increased SOD activity.TG-6 reduced TLR4,IκBα and NF-κB protein expression in cardiac tissue. Conclusion：TG-6 exerts strong favorable cardioprotective function on myocardial I/R injury, which may be related to anti-inflammatory and antioxidant activity.