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
岳改英,李景,解欣然,周旭升,李江敏子,谷玉红,易京红
摘要(Abstract):
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),与模型组大鼠比较,法舒地尔组、糖心宁高、等效剂量组大鼠JNK、P38MAPK蛋白表达均明显受到抑制(P<0.05)。结论糖心宁能减轻糖尿病心肌病大鼠的心室重构,其机制可能与抑制ROCK-MAPK信号通路有关。
关键词(KeyWords): 糖尿病心肌病;心室重构;糖心宁;ROCK-MAPK信号通路
基金项目(Foundation): 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)
作者(Author): 岳改英,李景,解欣然,周旭升,李江敏子,谷玉红,易京红
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