葡萄籽原花青素对糖尿病小鼠心室重构的保护作用

The protective effects of grape seed proanthocyanidins on cardiac remodeling in diabetis mice

目的探讨葡萄籽原花青素(GSP)对糖尿病小鼠心脏损伤的保护作用及作用机制。方法采用腹腔注射四氧嘧啶制备1型糖尿病模型,造模成功后,随机分为模型组、GSP低、中、高剂量组(65、130、195 mg/kg)和二甲双胍(MET)阳性对照组(220 mg/kg)。同时设置空白对照组,各组灌胃给药30 d,对照和模型组给予0.9%氯化钠溶液灌胃。给药期间记录动态血糖、糖耐量和饮食饮水量的变化。连续给药30 d后,采用BL-420S生物机能实验系统检测小鼠心功能并计算心脏重量指数(HWI)和肾脏重量指数(KWI);苏木精-伊红(HE)染色和马松(Masson)染色观察组织病理学变化;酶联免疫吸附法和比色法检测血清学指标的改变;免疫荧光法和Western blot检测心脏组织蛋白表达的变化。结果与对照组相比,模型组小鼠血糖、糖耐量、饮食饮水量明显升高;血流动力学、病理形态学、血清学指标发生明显异常改变,如心肌组织内皮素A(ETA)明显升高,内皮型一氧化氮合酶(eNOS)明显降低等。与模型组相比,给药组和MET组均能显著改善上述指标。结论GSP对糖尿病心脏损伤具有一定的保护作用,其机制可能与抗氧化应激和改善内皮功能障碍有关。

Objective To investigate the protective effect of grape seed proanthocyanidins(GSP)on heart injury and its possible mechanism in diabetic mice.Methods Diabetic mice was induced by intraperitoneal injection of alloxan.The mice were randomly divided into model group,GSP low,middle and high dose group(65,130,195 mg/kg)and metformin positive control group(220 mg/kg).Meanwhile,the control group was set up.The control group and model group were given normal saline.Dynamic blood glucose,glucose tolerance and water intake were recorded during the administration.At the end of the experiment,BL-420S was used to detect the hemodynamics of mice;the heart weight and kidney weight index were calculated;pathologicalchanges were observed by pathological staining;serological indexes were detected by enzyme-linked immunosorbent assay and colorimetry;protein expression in heart tissue was observed by immunofluorescence and western blotting.Results Compared with the control group,the blood glucose,glucose tolerance,diet and drinking water were significantly higher in the model group;the cardiac function,pathomorphology,serological indexes had changed abnormally,such as the increase of endothelin-1 A receptor(ETA)and the decrease of the endothelial nitric oxide synthase(eNOS).GSP and metformin could significantly improve the above indicators.Conclusion GSP has protective effect on heart injury in diabetic mice,and its mechanism may be related to anti-oxidant stress and improvement of endothelial dysfunction.