目的 观察吡格列酮对2型糖尿病（T2DM）模型大鼠心肌纤维化的影响。方法 清洁级雄性SD大鼠随机分为对照组和模型组，对照组喂饲正常食物，模型组喂饲高脂饲料，2周后模型组大鼠一次性尾iv链脲佐菌素（STZ）50 mg/kg。造模成功大鼠又随机分为模型组和吡格列酮低、高剂量（5、10 mg/kg）组，除对照组，其余大鼠继续给予高脂饲料，每天ig给药1次至12周。心室彩色超声检测心输出量（CO）、左心室舒张末期（LVIDd）和收缩末期内径（LVIDs）；眼眶采血，应用葡萄糖氧化酶法检测试剂盒测血糖；天狼猩红染色计算胶原容积分数；ELISA法检测外周血肿瘤坏死因子α（TNF-α）和白介素-6（IL-6）水平；Western blotting检测心肌组织转化生长因子β1（TGF-β1）和Smad3蛋白表达。结果 与模型组比较，吡格列酮组血糖、LVIDd和LVIDs显著降低（P<0.05、0.01），CO显著升高（P<0.05、0.01）；吡格列酮低、高剂量组心肌间质胶原纤维显著减少，胶原容积分数显著降低（P<0.01）；吡格列酮组TNF-α和IL-6表达水平显著降低（P<0.01）；吡格列酮组TGF-β1和Smad3蛋白相对表达量显著降低（P<0.01）；作用均呈剂量相关性。结论 吡格列酮通过抑制炎症反应以及TGF-β1/Smad3信号通路，发挥抗糖尿病大鼠心肌纤维化的作用。

Objective To observe the effect of pioglitazone on myocardial fibrosis in Type 2 diabetes mellitus (T2DM) rats. Methods SD rats were divided into control group and T2DM model group. Rats in control group was fed with normal food. T2DM model group was given 40% calories for fat. After two weeks, the T2DM model group was injected with STZ (50 mg/kg). T2DM rats were divided into:model group, pioglitazone low and high dose group. Except for the control group, the rest of the rats were continued given high-fat diet, once ig a day to 12 weeks. Cardiac output (CO), left ventricular end diastolic (LVIDD) and end systolic diameter (LVIDS) were measured by echocardiography. Blood samples were collected from orbit and blood glucose was measured by glucose oxidase method. Collagen volume fraction was calculated by Sirius red staining. TNF-α and IL-6 was detected by ELISA analysis. TGF-β1 and Smad3 was detected by Western blotting. Results Blood glucose, LVIDd and LVIDds in pioglitazone group were significantly lower than those in model group (P<0.05 and 0.01), while CO was significantly higher than that in model group (P<0.05). In pioglitazone low and high dose groups, myocardial interstitial collagen fibers and collagen volume fraction were significantly decreased compared with model group (P<0.01). The expression of TNF-a and IL-6 in pioglitazone group was lower than that in model group (P<0.01). The relative gray values of TGF-β1 and Smad3 in pioglitazone group was lower than that in model group (P<0.01). Conclusion Pioglitazone can inhibit inflammatory and TGF-β1/Smad3 path way to block myocardial fibrosis in diabetic rats.

R965.1

海南省自然科学基金资助项目（20168394）