·糖尿病基础研究·

　　戴启明 刘乃丰

　　作者单位：210009南京，东南大学附属中大医院心脏科

　　【摘要】目的探讨氨基胍抑制DM大鼠心肌间质纤维化的机制及其对心功能的影响。方法雄性SD大鼠30只，随机分成正常对照组(NC)、DM组和氨基胍干预(A)组，每组各10只。采用STZ一次性腹腔注射建立DM动物模型。12周后检测大鼠血清AGEs、左室心肌胶原含量、结缔组织生长因子(CTGF)mRNA和蛋白质表达及血流动力学。结果与NC组相比，DM大鼠血清AGEs的荧光值(7.21±2.2 vs 2.63±0.62，P<0.01)、左室心肌组织胶原含量 (16±3% vs 12±2%, P<0.01)及CTGFmRNA和蛋白质表达水平 (0.077±0.0037 vs 0.0102±0.0034，0.51±0.01 vs 0.34±0.02，P< 0.01) 均明显升高，心功能明显减低;应用氨基胍干预后上述异常明显减轻。结论氨基胍通过抑制AGEs的形成及心肌组织的CTGF的表达来逆转DM大鼠心肌间质纤维化并改善心脏功能。

　　【关键词】糖尿病;心肌;纤维化;心脏功能;糖基化终产物

　　doi:10.3969/j.issn.1006-6187.2012.03.019

　　Effect of aminoguanidine on myocardial interstitial fibrosis and cardiac function in diabetic ratsDAI Qi-ming,LIU Nai-feng.Department of Cardiology, Zhongda Hospital of Southeast University, Nanjing 210009, China

　　【Abstract】ObjectiveTo investigate the effect of aminoguanidine on myocardial interstitial fibrosis and cardiac function in diabetic rats, and explore the mechanism of the actions.Methods　Thirty male SD rats were randomly divided into 3 groups: normal control, STZ-induced diabetic rats, and diabetic rats treated with aminoguanidine. After 12 weeks, hemodynamics, advanced glycation end products (AGEs) in serum and values of collagen content , the expression of connective tissue growth factor (CTGF) mRNA and protein in the left ventricular tissue were measured.ResultsCompared with the control, AGEs fluorescence of serum(7.21±2.2 vs 2.63±0.62,P<0.01),collagen content (16±3% vs 12±2%, P<0.01), the expression of CTGF mRNA(0.077±0.0037 vs 0.0102±0.0034,P< 0.01) and protein (0.51±0.01 vs 0.34±0.02，P< 0.01) of myocardium were significantly increased in the diabetic group. The cardiac function was significantly lower in the diabetic group than in the control group. However, the above-mentioned abnormalities were obviously attenuated by administration of aminoguanidine.ConclusionsAGEs play an important role in myocardial interstitial fibrosis of diabetic rats. Aminoguanidine can reverse the myocardial interstitial fibrosis and improve the cardiac function by inhibiting the formation of AGEs and down-regulating the over-expression of CTGF.

　　【Key words】Diabetes mellitus; Myocardium; Fibrosis; Cardiac function; Glycosylation end products, advanced