摘要
目的:观察罗格列酮对糖尿病大鼠心脏转化生长因子-β1(TGF-β1)/SMADs 信号转导通路的影响及对心脏重塑的作用。方法:30只雄性 SD 大鼠随机分成正常组、糖尿病组和罗格列酮组,每组10只。腹腔注射链脲菌素60 mg/kg 建立糖尿病模型。12周后,多导生理记录仪测定大鼠心功能;测定大鼠体质量、心脏质量并计算心脏质量/体质量;电镜观察心肌超微结构改变;苦味酸酸性复红染色观察心肌间质纤维化程度;逆转录多聚酶链反应(RT-PCR)测定大鼠心脏 SMAD3和 SMAD7信使核糖核酸(mRNA)水平,免疫组化法分析大鼠心脏 TGF-β1、SMAD3和 SMAD7的蛋白水平。结果:与正常组比较,糖尿病组心功能明显受损,心脏胶原含量显著增加(P<0.01),心脏质量/体质量显著增加(P<0.01),电镜超微结构显示心肌肌丝溶解、断裂,间质胶原增生,SMAD3 mRNA 表达水平明显增加(P<0.01),SMAD7mRNA 表达水平明显降低(P<0.01),TGF-β1和 SMAD3蛋白表达水平均增加(P<0.01),SMAD7蛋白表达水平降低(P<0.01)。应用罗格列酮干预后,心功能明显改善,胶原含量明显下降(P<0.05),心脏质量/体质量下降(P<0.05),超微结构破坏程度减轻,SMAD3 mRNA 表达水平降低(P<0.01),SMAD7 mRNA 水平增加(P<0.01),TGF-β1和SMAD3蛋白表达水平均降低(P<0.05～0.01),SMAD7蛋白表达水平增加(P<0.01)。结论:罗格列酮能够明显改善链脲菌素糖尿病大鼠心脏重塑,改善心功能,影响 TGF-β1/SMADs 信号通路活化可能是其作用机制之一。
Objective ：To observe the effects of rosiglitazone on transforming growth factor -β1 （TGF-β1）/SMADs signal pathway in diabetic rat myocardium（DM） and cardiac remodeling. Methods：Thirty male SD rats were randomly divided into normal control, DM and rosiglitazone groups, each having 10 rats. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin （60mg/kg）. A cannula connected to a transducer was inserted into the heart to measure the cardiac function. The body weight, heart weight and heart weight/body weight （HW/BW） were measured. The ultrastructural changes were evaluated by electron microscope and collagen content was assessed by Van Gieson staining. The mRNA expression level of SMAD3 and SMAD7 were determined by RT-PCR. The protein level of TGF-β1 ,SMAD3 and SMAD7 were detected by immunohistochemistry. Results：Compared with the normal controls, diabetic rats experienced marked myocardium damage. Cardiac function, especially diastolic function was impaired, HW/BW （ P 〈 0. 01 ） and collagen content （ P 〈 0. 01 ） were much higher. Uhrastructural changes,such as myofilament fragmentation, blood capillary basement membrane thickening and interstitial fibrosis were observed. The protein level of TGF-β1was increased, mRNA and protein level of SMAD3 were significantly increased and SMAD7 was markedly decreased. Compared with diabetic rats, rosiglitazone treated rats experienced slightly myocardium damage. The protein level of TGF-β1 was decreased. The mRNA expression and protein level of SMAD3 were decreased and SMAD7 was remarkably inecreased. Conclusions：Rosiglitazone can retard the progression of cardiac remodeling of diabetic heart. The mechanism may be related to its effect on TGF-β1/SMADs signal pathway.
出处
《中国循环杂志》
CSCD
北大核心
2007年第6期463-467,共5页
Chinese Circulation Journal
