Objective To investigate the effect of morroniside on oxidative stress in heart failure rats induced by ligation of the left anterior descending coronary artery. Methods The rat model of heart failure was established by ligating the left anterior descending coronary artery and inducing myocardial infarction. The rats that survived the procedure were then divided into six groups: a model group, a low dose group of morroniside (60 mg / kg) , a medium-dose group of morroniside (120 mg / kg) , a high-dose group of morroniside (240 mg / kg) , captopril group (100 mg / kg) and the sham operation group was only threaded without ligation. Following a modelling period of 3 hours, the drugs were administered by gavage according to the corresponding drugs and dosage, once a day for a period of eight weeks. Hematoxylin eosin (HE) staining was used to detect the histopathological changes of the rat heart. The levels of SOD and MDA in the plasma of rats in each group were detected by WST-1 method and TBA method, respectively. Finally, Western blot analysis was used to detect the expression of SIRT1 and SIRT3 proteins in rat myocardium. Results Following a period of eight weeks, the result of HE staining demonstrated that, in comparison with the sham operation group, the myocardial cells in the model group exhibited a state of disarray, accompanied by the presence of broken and necrotic muscle fibers, as well as inflammatory cell infiltration. In comparison with the model group, the myocardial structure of rats in the morroniside group and captopril group was evidently enhanced and the infiltration of inflammatory cells was mitigated. The result of the SOD detection showed that the plasma SOD concentration in the model group was significantly lower than that in the sham operation group (P<0. 001) . In contrast, the morroniside group exhibited a significant increase in SOD concentration (P<0. 05,P<0. 01) , as did the Captopril group increased significantly ( P < 0. 01) . The result of the MDA test demonstrated that the concentration of MDA in the model group was significantly higher than that in the sham operation group (P< 0. 01) . In contrast, the morroniside group exhibited a significant decrease in MDA concentration (P<0. 05,P<0. 01) , and that in the Captopril group demonstrated a comparable decrease ( P<0. 01) .The result of the Western blot analysis demonstrated that the expression levels of SIRT1 and SIRT3 proteins in the model group were significantly lower than those in the sham operation group ( P<0. 05) . Compared with the model group, the expression level of morroniside in the High-dose group was significantly increased (P<0. 05) , and there was an increasing trend in the captopril group, though this was not statistically significant. Conclusion Morroniside may improve the oxidative stress injury in rats with heart failure subsequent to myocardial infarction by increasing the concentration of SOD in plasma, decreasing the concentration of MDA and Up-regulating the expression levels of SIRT1 and SIRT3 proteins, thereby reducing myocardial injury.

SIRT1 / 3;morroniside;heartfailure;oxidativestress;superoxidedismutase, malondialdehyde

目的 探讨莫诺苷对结扎冠状动脉左前降支致心力衰竭模型大鼠氧化应激反应的影响。 方法 采用结扎冠状动脉左前降支导致心肌梗死的方法建立大鼠心力衰竭模型,将造模成功的大鼠随机分为模型组、莫诺苷低剂量组(60 mg / kg) 、莫诺苷中剂量组(120 mg / kg) 、莫诺苷高剂量组( 240 mg / kg) 、卡托普利组( 100 mg / kg) 和假手术组(只穿线不结扎) 。 造模 3 h 后,按照对应的药物及给药剂量进行灌胃给药,每天 1 次,连续给药 8 周。 苏木精-伊红染色法( HE)检测大鼠心脏组织病理学变化;WST-1 法检测各组大鼠血浆中 SOD 水平;TBA 法检测各组大鼠血浆中MDA 的水平;Western blot 检测大鼠心肌组织中 SIRT1、SIRT3 蛋白表达。 结果 给药 8 周后,HE 染色结果显示,与假手术组相比,模型组大鼠心肌细胞排列紊乱,肌纤维出现断裂、坏死,且伴有炎性细胞浸润;与模型组相比,莫诺苷组和卡托普利组大鼠心肌结构得到明显的改善、炎性细胞浸润缓解。 SOD 检测结果显示:与假手术组相比,模型组血浆 SOD 浓度显著降低(P<0. 001) ;与模型组相比,莫诺苷组 SOD 浓度显著升高( P< 0. 05,P< 0. 01) ,卡托普利组 SOD 浓度显著升高( P< 0. 05) 。 MDA 检测结果显示:与假手术组相比,模型组 MDA 浓度显著升高( P< 0. 001) ;与模型组相比,莫诺苷组 MDA 浓度显著降低 ( P < 0. 05,P < 0. 01) ,卡托普利组 MDA 浓度显著降 低 ( P < 0. 05) 。Western blot 结果显示:与假手术组相比,模型组 SIRT1、SIRT3 蛋白表达量明显降低(P<0. 05) ;与模型组相比,莫诺苷高剂量组表达量明显升高(P<0. 05) ,卡托普利组有升高趋势,但无统计学差异。 结论 莫诺苷可能通过提高血浆中 SOD 浓度、降低 MDA 浓度,上调 SIRT1、SIRT3 蛋白表达水平来改善心肌梗死后心力衰竭大鼠氧化应激损伤,从而减轻心肌损伤。

SIRT1 / 3, 莫诺苷, 心力衰竭, 氧化应激, 超氧化物歧化酶, 丙二醛