心肌营养素-1和结缔组织增长因子在糖尿病大鼠心肌中的表达及厄贝沙坦的干预作用

目的通过观察心肌营养素-1（CT—1）mRNA和结缔组织增长因子（CTGF）在糖尿病大鼠心肌中的动态表达以及厄贝沙坦干预的影响，探讨CT—1和CTGF在糖尿病心肌病（DMCM）发病机制中的作用。方法SD雄性大鼠78只，随机分为对照组和糖尿病组。用链脲佐菌素（STZ）一次性腹腔注射建立糖尿病模型后，糖尿病组再为厄贝沙坦治疗组及糖尿病未治疗组。治疗组以厄贝沙坦灌服12周。分别在病程2、4、6、8、10、12周处死各组大鼠。称量体重（BW）、全心重量（HW）、左室重量（LVW），计算心体比（HW／BW）和左室重量指数（LVWI）。检测心肌CT—1 mRNA和CTGF的表达水平；心肌胶原（Col）和心肌血管紧张素（AngⅡ）含量。观察心肌超微结构病理改变。结果糖尿病组大鼠的HW／BW、LVWI明显高于正常对照组（P〈0．01），厄贝沙坦治疗组大鼠的HW／BW、LVWI明显低于糖尿病组（P〈0．01），但仍高于正常对照组（P〈0．01）。厄贝沙坦组心肌细胞变性、坏死程度和范围较糖尿病组明显减轻。糖尿病组大鼠CT—1 mRNA、CTGF表达明显卜调，随病程延长呈升高趋势（P〈0．01），心肌col、AngⅡ含量较正常对照组明显升高（P〈0．01）。而厄贝沙坦治疗组大鼠的CTI mRNA、CTGF表达与糖尿病组相比较下调（P〈0．01）；心肌Col、AngⅡ含量明显低于糖尿病组（P〈0．05）。糖尿病组大鼠心室CT—1mRNA、CTGF和心室局部Col、AngⅡ含量呈明显正相关。结论糖尿病大鼠心肌CT—1mRNA、CTGF表达上调与心肌肥大、间质纤化密切相关，在糖尿病心肌病的心室重构中起重要作用。厄贝沙坦町减轻糖尿病心肌病的心室重构，其心肌保护作用机制可能与其下调CT—1和CTGF水平有关。

EXPRESSION OF CARDIOTRPOHIN-1mRNA AND CTGF IN CARDIOMYOPATHY OF DIABETIC RATS AND THE EFFECT OF IRBESARTAN

Objective To investigate the expression of cardiotrophin-1 （CT-1） mRNA and connective tissue growth factor （CTGF） in cardiomyopathy of diabetic rats and the intervention of Irbesartan, and to probe into the role of CT-1 and CTGF in the diabetic mellitus cardiomyopathy. Methods Seventy eight male SD rats were randomized into 2 groups： the control group and the diabetic group. Diabetes was induced by intraperitoneal injection of STZ, and the rats of the diabetics group were subdivided into 2 groups： Irbesartan group and untreated group. Rats of the Irbesartan group were treated with Irbesartan for 12weeks. Rats were killed at 2weeks, 4weeks, 6weeks, 8weeks, 10weeks, 12weeks respectively. Of each rat were measured body weight （BW） ,heart weight （HW） ,left heart weight （LVW） ,heart weight/body weight （HW/BW） and left ventricular weight index （LVWI） . The pathological changes of myocardial ultrastructure were observed. CT-1 mRNA, CTGF, myocardial AngII （Ang Ⅱ ） and collagen contents（COL） were measured respectively. Results LVWI and HW/BW of the diabetic groups were significantly higher than that of the control group （P〈0.01）. HW/BW and LVWI of the Irbesartan group were lower than those of the umtrated group （P〈0.01） and higher than those of the control group （P〈0.01）. Pathological changes of cardiocyte degeneration and cellular necrosis in the lrbesartan group were lessened than in the unfreated group. The CT- 1 mRNA and CTGF expression of the diabetic groups was increased significantly with the development of diabetes （P〈0.01）. And the Col and AngII contents in the diabetic groups were higher than those in the control group （P〈0.01）. The CT-1 mRNA and CTGF expression of the Irbesartan group was lower than those of the untreated group （P〈0.01）. Also, Col and AngⅡ of cardiomyopathy were lower than those of the untreated group （P〈0.05）. Cardiac ventricle CT-1 mRNA and CTGF were positively correleted with Col and AngⅡ. Conclusion Upregulation of CTGF and CT-1mRNA is strongly correlated with the concomitant accumulation of extracelluar matrix component, and is involved in the onset and progression of diabetic cardiomyopathy. Down-regulating the overexpression of CT-1 mRNA and CTGF in diabetic is an underlying mechanism of Irbesartan in the prevention of myocardial fibrosis and cardiac protection.