目的 观察糖尿病(DM)大鼠和正常大鼠冠状动脉RhoA及Rho激酶(ROCK)表达水平及PPAR-γ激动剂吡格列酮(PIO)对糖尿病大鼠糖脂代谢及冠状动脉组织RhoA及ROCK表达水平的影响.方法 30只雄性Sprague-Dawley大鼠随机分为3组,对照组予普通饮食;DM组给予高果糖饮食+链脲佐菌素(25 mg/kg)造模,PIO干预组在糖尿病组基础上给予吡格列酮10 mg·kg-1 ·d-1干预.4周后采血检测血糖、血脂及胰岛素水平,分离冠状动脉采用Western Blot法测定各组大鼠冠状动脉组织中RhoA、ROCK1、ROCK2蛋白表达水平.结果 吡格列酮可显著降低DM大鼠胆固醇、三酰甘油及空腹胰岛素水平(均为P <0.05).与对照组比较,DM组RhoA(F =5.131,P=0.019)、ROCK2蛋白表达水平升高(F=6.953,P=0.011),ROCK1蛋白表达水平差异无统计学意义.给予PIO干预后ROCK2蛋白表达水平明显降低,差异具有统计学意义(F =4.323,P=0.045).结论 PIO可显著改善糖尿病大鼠胰岛素抵抗状态,降低TC及TG水平.糖尿病大鼠冠状动脉RhoA/ROCK蛋白表达增加,吡格列酮可显著降低糖尿病大鼠冠状动脉组织ROCK2蛋白表达水平.
Objective To observe RhoA and ROCK protein expression level in diabetes mellitus (DM) rat's coronary artery tissue and identify whether pioglitazone (PIO) could affect RhoA and ROCK protein expression level in DM Rat's coronary artery.Methods A total of 30 male Sprague-Dawley (SD) Rats were randomly divided into 3 groups (10 in each group),control group (fed with normal diet),DM group [create model by high fructose diet plus Streptozotocin(25 mg/kg) injection] and PIO group (DM plus pioglitazone 10 mg· kg-1 · d-1).After 4 weeks treatment,blood samples were collected for glucose,serum lipid and serum insulin test.Coronary arteries were isolated for Westen blot assay to identify RhoA,ROCK1,ROCK2 protein expression level.Results The RhoA,ROCK2 protein expression levels were significantly elevated in DM group than in control group (F =5.131,P =0.019 ; F =6.953,P =0.011,respectively),and ROCK1 protein expression level was similar between the two groups.The ROCK2 protein expression level remarkably decreased in PIO group(F =4.323,P =0.045).RhoA protein expression level was lower in PIO group than in DM group but no statistic difference.Conclusions Pioglitazone can remarkably reverse DM rat's insulin resistence,lower TC and TG level.The RhoA/ROCK protein expression is increased in DM rat's coronary artery and Pioglitazone can significantly down regulate ROCK2 protein express level in the DM rat's coronary artery.