丹参多酚酸盐联合三七总皂苷对2型糖尿病模型大鼠心肌的影响及作用机制

Effects and mechanisms of Salvianolate combined with Panax notoginsenosidum on diabetic cardiomyopathy of type 2 diabetic model rats

目的:探讨丹参多酚酸盐联合三七总皂苷对2型糖尿病模型大鼠心肌的影响及作用机制。方法:选取50只健康SD雄性大鼠作为研究对象。采用随机数字表法抽取40只造模为2型糖尿病大鼠模型,采用链脲佐菌素腹腔注射并高脂饮食法建动物模型,成模后将模型组分为4组,高、中、低三个剂量组30只、模型组10只、正常对照组10只。其中高、中、低三个组按预定剂量给予丹参多酚酸盐和三七总皂苷连续腹腔注射8周,模型组及对照组注射等量生理盐水。比较两组注射前后空腹血糖(FPG)、心肌组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)含量水平;采用Masson染色观察大鼠心肌组织纤维化程度,计算各组心肌胶原容积分数(CVF);采用分光光度试剂盒检测心肌组织Caspase-3、Caspase-8、Caspase-9活性。结果:注射后各高、中、低三个剂量组FPG水平均明显低于对照组,高剂量组FPG水平明显低于低剂量组,差异均有统计学意义(P<0.05);高、中、低三个剂量组SOD、GSH-Px水平均明显高于模型组,MDA水平明显低于模型组,高剂量组SOD、GSH-Px水平明显高于低剂量组,差异均有统计学意义(P<0.05);高、中二个剂量组CVF均明显小于低剂量组,Caspase-3、Caspase-9活性均显著低于低剂量组,差异均有统计学意义(P<0.05)。结论:丹参多酚酸盐联合三七总皂苷能够显著降低Ⅱ型糖尿病模型大鼠的血糖水平,延缓心肌纤维化病变,其机制可能与抑制Caspase-9活性有关。

Objective： To investigate effects and mechanisms of Salvianolate combined with Panax notoginsenosidum on diabetic cardiomyopathy of type 2 diabetic model rats. Methods： A total of 50 healthy SD rats were selected as the research objects and divided into normal control group （n = 10） and experimental group （n = 40）. The experimental group was given Streptozotocin by intraperitoneal injection and high fat diet to establish the diabetic models, which were then subdivided into high dose group （n = 10）, moderate dose group （n = 10）, low dose group （n = 10） and model group （n = 10）. Further, the high dose group, moderate dose group andlow dose group were given the prescribed Salvianolate combined with Panax notoginsenosidum by intraperitoneal injection for 8 weeks,while the model group and the control group used the equivalent physiological saline. The levels of fasting plasma glucose （FPG）, superoxide dismutase （SOD）, glutathion peroxidase （GSH-Px）, and malondialdehyde （MDA） of the two groups before and after the injection were compared. The myocardial fibrosis was observed by Masson staining. The collagen volume fraction （CVF） was calculatedand the activities of Caspase-3, Caspase-8 and Caspase-9 were detected by commercial kit. Results： After the injection, the FPGlevels of the high dose group, moderate dose group and low dose group were significantly higher than that of the control group, the FPGlevel of the high dose group was obviously lower than that of the low dose group, and the differences were statistically significant （P〈0. 05）. The levels of SOD and GSH-Px of the high dose group, moderate dose group and low dose group were significantly higher thanthat of the model group, the MDA level was obviously lower than that of the model group, the levels of SOD and GSH-Px of the highdose group were obviously higher than those of the low dose group, and the differences were statistically significant （P〈0. 05）. Moreover, the levels of CVF of the high dose group and moderate dose group were significantly lower than that of the low dose group, the activities of Caspase-3 and Caspase-9 were obviously lower than those of the low dose group, and the differences were statistically significant （P〈0. 05）. Conclusions： Salvianolate combined with Panax notoginsenosidum could improve the plasma glucose levels of thetype 2 diabetic model rats and delay myocardial fibrosis. The mechanism of myocardium protection may be correlated with the activity ofCaspase-9.