目的 觀察吡格列酮對2型糖尿?。═2DM）模型大鼠心肌纖維化的影響。方法 清潔級雄性SD大鼠隨機分為對照組和模型組，對照組喂飼正常食物，模型組喂飼高脂飼料，2周后模型組大鼠一次性尾iv鏈脲佐菌素（STZ）50 mg/kg。造模成功大鼠又隨機分為模型組和吡格列酮低、高劑量（5、10 mg/kg）組，除對照組，其余大鼠繼續(xù)給予高脂飼料，每天ig給藥1次至12周。心室彩色超聲檢測心輸出量（CO）、左心室舒張末期（LVIDd）和收縮末期內(nèi)徑（LVIDs）；眼眶采血，應用葡萄糖氧化酶法檢測試劑盒測血糖；天狼猩紅染色計算膠原容積分數(shù)；ELISA法檢測外周血腫瘤壞死因子α（TNF-α）和白介素-6（IL-6）水平；Western blotting檢測心肌組織轉(zhuǎn)化生長因子β1（TGF-β1）和Smad3蛋白表達。結(jié)果 與模型組比較，吡格列酮組血糖、LVIDd和LVIDs顯著降低（P<0.05、0.01），CO顯著升高（P<0.05、0.01）；吡格列酮低、高劑量組心肌間質(zhì)膠原纖維顯著減少，膠原容積分數(shù)顯著降低（P<0.01）；吡格列酮組TNF-α和IL-6表達水平顯著降低（P<0.01）；吡格列酮組TGF-β1和Smad3蛋白相對表達量顯著降低（P<0.01）；作用均呈劑量相關(guān)性。結(jié)論 吡格列酮通過抑制炎癥反應以及TGF-β1/Smad3信號通路，發(fā)揮抗糖尿病大鼠心肌纖維化的作用。

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

海南省自然科學基金資助項目（20168394）