白芍总苷对大鼠心肌缺血再灌注损伤保护作用及其机制研究

Protection and mechanism of total glucosides of paeony on myocardial ischemia-reperfusion injury in rats

目的:研究白芍总苷(TGP)对大鼠心肌缺血再灌注损伤的保护作用。方法:通过夹闭冠状动脉30min后松夹的方法制备心肌缺血再灌注大鼠模型,取80只大鼠随机分为心肌缺血再灌注模型对照组、白芍总苷60、120和240mg/kg治疗组和复方丹参滴丸135mg/kg治疗组,并另取16只同龄大鼠设假手术组,术后立即灌胃给药,4周后,测定各组大鼠心脏/体质量比,由TTC染色测定各组大鼠心肌梗死面积,通过HE染色方法观察各组大鼠心肌组织病理学改变;测定各组大鼠血清中心肌酶(AST、CPK、LDH)含量以及总抗氧化能力(T-AOC)水平;测定心肌组织中抗氧化酶(SOD、GSH-Px、CAT)活性以及丙二醛(MDA)含量;通过酶联免疫法(ELIAS)测定各组大鼠血清中白细胞介素-1(IL-1)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平。结果:较模型对照组,白芍总苷120和240mg/kg组大鼠心脏/体质量比和心肌梗死面积均显著降低;白芍总苷治疗组大鼠心肌组织病变好转,其中以240mg/kg治疗组效果最为显著;白芍总苷120和240mg/kg治疗组大鼠血清中AST、CPK、LDH含量及IL-6水平均显著降低,心肌组织中SOD、CAT活性显著升高且MDA含量显著降低,其中240mg/kg治疗组血清中T-AOC、IL-1、TNF-α水平和心肌组织中GSH-Px活性显著升高。结论:白芍总苷能够有效减轻心脏水肿,减小心肌组织梗死,改善组织病理学改变,提示白芍总苷对大鼠心肌缺血再灌注损伤具有剂量依赖性的保护作用,其作用机制可能与其能够增强抗氧化酶活性、抑制氧化应激损伤,改善心功能有关。

Objective： To investigate the protection and mechanism of total glucosides of paeony（ TGP） on myocardial ischemia-reperfusion injury in rats. Methods： 80 rat models were randomly devided into five groups： myocardial ischemia-reperfusion control group,TGP 60,120 and 240 mg / kg treated groups,and Fufangdanshen diwan（ 135 mg / kg） treated group,and selcted another 16 same-aged rats as sham operation group. Four weeks later,the ratio of heart weight and body weight were detected,the areas of myocardial infarction were analysised by TTC staining,the histopathological changes was observed by HE staining; the level of T-AOC and the content of AST,CPK,LDH in serum were determined; and the level of IL-1,IL-6,TNF-α in serum were determined; the activity of SOD,GSH-Px,CAT and the content of MDA in myocardial tissue were determined. Results： Compared with myocardial ischemia- reperfusion control group,the ratio of heart weight and body weight of TGP 120 and 240 mg / kg treated groups and the areas of myocardial infarction were significantly decreased（ P〈0. 05,P 〈0.01）; the histopathological changes of TGP treated groups were significantly improved,especially the 240 mg / kg treated group. The content of AST,CPK,LDH,IL-6 in serum of TGP 120,240 mg / kg treated groups were significantly decreased（ P〈0. 05,P〈0. 01）,the activity of SOD,CAT were significantly increased and the content of MDA in myocardial tissue significantly decreased（ P〈0. 05,P〈0. 01）; the level of T-AOC,IL-1,TNF-α in serum and the the activity of GSH-Px in myocardial tissue of TGP 240 mg / kg treated group was significantly increased（ P〈0. 05,P〈0. 01）. Conclusion： TGP could effectively lower the cardiac edema and the areas of myocardial infarction,inhibit the histopathological changes,suggesting that TGP had dose-dependent protective effects against myocardial ischemia-reperfusion injury in rats,which perhaps related to its effects of enhancing the activity of antioxidant enzymes,inhibiting the oxidative stress,improving heart function and inhibiting the inflammation.