中文摘要：

目的 观察球形脂联素（gAd）对2型糖尿病（T2DM）大鼠动脉粥样硬化的影响并探讨其作用机制.方法 90只雄性SD大鼠按随机数字表法分为正常对照组（N组,n=24）和T2DM造模组（n=66）,成模的53只再分为T2DM组（D组,n=26）、干预组（A组,n=27）.A组予gAd 10μg·kg-1·d-1腹腔推注,余两组予等量生理盐水.各组分别于4、8、12周（w）末随机取8只大鼠麻醉后采血,备测生化指标,留取胸主动脉,行HE染色后光镜观察其形态学改变,并用免疫组化法测Ⅰ型胶原蛋白（Col-1）的表达,应用Western blotting、实时荧光定量聚合酶链反应法测转化生子因子β1（TGF-β1）、Smad3、Smad7蛋白及其mRNA的表达.统计学采用单因素方差分析和LSD-t检验.结果 （1）在各时间段中,与N组相比,D组胸主动脉出现动脉粥样硬化改变,且随时间延长,病变逐渐加重,TGF-β1、Smad3蛋白及Col-1表达明显增多（12 w：1.28±0.01比0.99±0.02、1.08±0.01比0.84±0.01、183.3±0.6比200.7±2.1,t=25.108、20.779、15.011,均P〈0.05）,而Smad7蛋白减少（12 w：0.72±0.02比1.10±0.02,t=30.018,P〈0.05）.（2）与同期D组比较,A组胸主动脉粥样硬化病变减轻,12 w时TGF-β1、Smad3及Col-1蛋白表达分别为1.05±0.01、0.81±0.02、196.3±1.2,明显低于D组（t=19.913、23.377、11.258,均P〈0.05）,而Smad7蛋白增多（12 w为0.99±0.01,t=21.404,P〈0.05）.且随gAd干预时间延长,病变逐渐减轻,TGF-β1、Smad3及Col-1逐渐减少,Smad7逐渐增多（均P〈0.05）.结论 gAd可通过上调Smad7或下调TGF-β1、Smad3进而抑制TGF-β1/Smads传导通路,发挥抗血管壁纤维化作用,从而缓解T2DM大鼠动脉粥样硬化进程.

英文摘要：

Objective To explore the mechanism and effects of globular adiponectin （gAd） on atherosclerosis in rats with type 2 diabetes mellitus （T2DM）. Methods Ninety male Sprague-Dawley rats were divided into control group （group N, n=24） and T2DM model group （n=66） according to the method of random number table. Similarly, 53 successful modeling diabetic rats were randomly divided into T2DM group （group D, n=26） and intervention group （group A, n=27）. Rats in group A were administrated with gAd in dose of 10 μg·kg-1·d-1, and rats in the other two groups were administrated with saline respectively. At the end of 4, 8 and 12 weeks （w）, serum biochemical indexes were tested in 8 rats collected randomly from each group, respectively. In the mean time, atherosclerotic changes of thoracic aorta were observed by HE staining, and the expressions of type 1 collagen （Col-1） were detected by immunohistochemistry. The protein and mRNA expressions of transforming growth factor β1 （TGF-β1）, Smad3, Smad7 were detected by Western blotting and real time fluorescent quantitative polymerase chain reaction, respectively. Statistical analysis was performed by using one way analysis of variance and LSD-t test. Results In each period, compared with group N, in group D, atherosclerotic changes of thoracic aorta appeared, the lesions worsened gradually with staining time, and the expressions of TGF-β1, Smad3 and Col-1 increased significantly （12 w：1.28±0.01 vs 0.99±0.02, 1.08±0.01 vs 0.84±0.01, 183.3±0.6 vs 200.7±2.1, t=25.108, 20.779, 15.011, all P〈 0.05）, while the expression of Smad7 decreased （12 w： 0.72 ± 0.02 vs 1.10 ± 0.02, t=30.018, P〈0.05）.Compared with group D, in group A, atherosclerotic lesions of thoracic aorta were slight, and the expressions of TGF-β1, Smad3 and Col-1 decreased significantly （12 w： 1.05±0.01, 0.81±0.02, 196.3±1.2, t=19.913,23.377, 11.258, all P〈0.05）, while the expression of Smad7 increased （12 w： 0.99±0.01, t=21.404, P〈0.05）.Wi