阿托伐他汀通过RGS6改善糖尿病心肌病大鼠心功能的作用及其机制研究

目的:探讨阿托伐他汀通过调节RGS6/NAD(P)H氧化酶/活性氧生成通路保护糖尿病心肌病大鼠心功能的药理作用机制。方法:40只6周龄雄性Wistar大鼠按随机数字表法随机分为对照组,糖尿病心肌病模型组,低剂量阿托伐他汀组,高剂量阿托伐他汀组,每组10只。实验过程中动态监测大鼠体质量及血脂水平;实验结束后脉冲多普勒检测各组大鼠心功能指标;组织活性氧检测试剂盒检测心肌组织中活性氧的水平;免疫组化法检测大鼠心肌组织中RGS6的表达;Western blot法检测大鼠心肌组织中RGS6及NAD (P)H氧化酶活性亚单位p47phox和p67phox的水平。结果:与对照组相比,糖尿病心肌病模型大鼠体质量明显减少(P0.01),血脂水平明显升高(P0.01),心脏E/A、LVEF、FS值降低(P0.01),心肌组织活性氧生成明显增多(P0.01),心肌组织RGS6及p47phox、p67phox表达明显上调(P0.01),而不同剂量阿托伐他汀干预均可有效逆转上述指标的改变。结论:阿托伐他汀对糖尿病心肌病大鼠的心脏具有明显保护作用,其机制可能与对RGS6/NAD(P)H氧化酶/活性氧生成通路的抑制有关。

Atorvastatin Improves Cardiac Function in Diabetic Cardiomyopathy Rats by Regulating RGS6

ABSTRACT Objective: To investigate the pharmacological mechanism of atorvastatin in protecting cardiac function in diabetic cardiomyopathy rats by regulating RGS6/NAD(P)H oxidase/reactive oxygen (ROS) production pathway. Methods: 40 6-week-old male Wistar rats were randomly divided into control group, diabetic cardiomyopathy model group, low-dose atorvastatin group and high-dose atorvastatin group according to the random number table method (10 rats in each group). During the experiment, the body mass and lipid levels of rats were monitored dynamically. After the experiment, pulse doppler method was used to detect the cardiac function indexes of rats in each group. Tissue ROS detection kits were used to detect the ROS levels in myocardial tissues. The expression of RGS6 in myocardial tissue was measured by immunohistochemistry and Western blot. The levels of RGS6 and NAD(P)H oxidase subunits p47 ^phox and p67 ^phox in rat myocardial tissues were detected by Western blot. Results: Compared with control group, the rats from diabetic cardiomyopathy model group displayed significant decreased body mass (P<0.01), increased levels of blood lipids (P<0.01), lower E/A heart, LVEF, FS value (P<0.01), increased production of ROS in myocardial tissue (P<0.01), enhanced expressions of RGS6, p47 ^phox and p67 ^phox in myocardial tissues (P<0.01), while different dose of atorvastatin intervention can effectively reverse these changes. Conclusion: Atorvastatin has a significant protective effect on the heart of diabetic cardiomyopathy rats, and its mechanism may be related to the inhibition of RGS6/NAD(P)H oxidase/ROS production pathway.