基于ROCK-MAPK通路观察糖心宁干预糖尿病心肌病作用机制研究  

Mechanism Research on the Effect of Tangxinning on Diabetic Cardiomyopathy Based on ROCK-MAPK Signal Pathway

作　　者：岳改英[1,2] 李景[1] 解欣然[3] 周旭升[1] 李江敏子 谷玉红[1] 易京红[1] 

机构地区：[1]首都医科大学附属北京中医医院,北京100010 [2]北京市房山区韩村河镇社区卫生服务中心,北京102423 [3]北京市中医研究所,北京100010

出　　处：《中国中医急症》2017年第1期26-29,32,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：首都中医药研究专项一般项目(15ZY15);首都医科大学附属北京中医医院"育苗计划"院级课题(2014YM-07)

摘　　要：目的观察糖心宁对糖尿病心肌病大鼠心肌组织ROCK、JNK及P38MAPK蛋白表达的影响,探讨其对ROCK-MAPK信号通路的作用机制。方法采用链脲佐菌素制备糖尿病心肌病大鼠模型,40只雄性SD大鼠随机分为空白组、模型组、法舒地尔组、糖心宁高剂量组、糖心宁等效剂量组各8只。空白组及模型组灌服等量清洁饮用水,法舒地尔组给予法舒地尔腹腔注射,糖心宁组灌服中药糖心宁。给药8周后处死大鼠,计算左心室肥厚指数,检测血糖、血脂水平;HE染色观察心肌细胞形态学变化;免疫组化法检测心肌组织ROCK、JNK、P38MAPK蛋白表达情况。结果给药8周末,模型组大鼠空腹血糖、甘油三酯明显高于空白组(均P<0.05);与模型组比较,法舒地尔组、糖心宁高剂量组、糖心宁等效剂量组甘油三酯水平明显降低(均P<0.05),但空腹血糖未见明显变化(均P>0.05)。模型组大鼠心肌肥厚指数明显高于空白组(P<0.05);与模型组比较,法舒地尔组、糖心宁高剂量组、糖心宁等效剂量组心肌肥厚指数均低于模型组(P<0.05)。HE染色光镜下观察,空白组大鼠心肌细胞肌节完整,肌丝、线粒体排列比较整齐。模型组大鼠心肌细胞肿胀,肌丝排列稀疏,肌丝断裂、溶解,心肌出现大面积玻璃样变性及坏死。糖心宁高剂量组、糖心宁等效剂量组、法舒地尔组大鼠心肌细胞肿胀,肌丝排列均较模型组有明显好转。与空白组大鼠比较,模型组大鼠的ROCK1蛋白表达显著增加(P<0.05),而ROCK2蛋白表达未见明显增加(P>0.05)。与模型组大鼠比较,法舒地尔组、糖心宁高剂量组、糖心宁等效剂量组的ROCK1蛋白表达受到显著抑制(P<0.05),ROCK2蛋白表达未见明显改变(P>0.05)。与法舒地尔组比较,糖心宁高剂量组明显抑制ROCK1蛋白表达(P<0.05),而糖心宁等效剂量组则并不明显(P>0.05)。与空白组大鼠比较,模型组大鼠的JNK、P38MAPK蛋白表达均显著增加(P<0.05),�Objective： To observe the effect of Tangxinning on the expression of ROCK,JNK and P38MAPK protein in myocardium of diabetic rats with cardiomyopathy, and to explore its mechanism of ROCK-MAPK signal pathway. Methods： Diabetic cardiomyopathy rats were induced by streptozotocin. The rats were randomly divided into blank group,model group ,fasudil group, Tangxirming high dose group and Tangxinning equivalent dose group with 8 cases in each group. The blank control group and the model group were given the same amount of clean drinking water. The fasudil group was given intraperitoneal injection of fasudil,the Tangxinning group was given Chinese medicine Tangxinning. After 8 weeks, the rats were sacrificed and the left ventricular hypertrophy index was calculated and the levels of blood glucose and lipid were measured. The morphological changes of myocardium were observed by HE staining. The expression of ROCK,JNK and P38MAPK protein in myocardium was detected by immunohistochemistry. Results： Compared with the model group ,the left ventricular hypertrophy was significantly decreased in the fasudil group,the Tangxinning high-dose group and the Tangxinning equivalentdose group （P〈 0.05 ）. The improvement on the swelling of the cardiomyocytes was significant （P〈 0.05 ）,and the expression of ROCK1 ,JNK and P38MAPK was decreased significantly,but no significant changes in ROCK2 protein expression. Conclusion： Tangxinning can reduce the ventricular remodeling in rats with diabetic cardiomyopathy, and its mechanism may be related to inhibition of ROCK-MAPK signaling pathway.

关 键 词：糖尿病心肌病 心室重构 糖心宁 ROCK-MAPK信号通路 

分 类 号：R285.5[医药卫生—中药学]