结缔组织生长因子在慢性心力衰竭大鼠心肌纤维化中的表达

Expression of connective tissue growth factor in myocardial fibrosis of rats with chronic heart failure

目的研究结缔组织生长因子(CTGF)的表达与慢性心力衰竭(CHF)大鼠心肌纤维化的关系。方法选择Wistar雄性大鼠45只,随机取8只为假手术组,其余37只大鼠采用肾上腹主动脉缩窄法制作CHF模型,4周后随机取10只大鼠测血流动力学证实造模成功,存活的24只大鼠随机分为CHF 1 d组,CHF 7 d组,CHF 14 d组,每组8只。各组测心肌胶原容积分数(CVF)及左心室重量指数(LVMI),用HE和Masson染色法观察左心室心肌组织形态的改变。用RT-PCR和Western blot法检测CTGF mRNA及蛋白表达水平。结果与假手术组比较,CHF 1 d组、CHF 7 d组和CHF 14 d组CVF和LVMI明显升高(P<0.01),与CHF 1 d组比较,CHF 7 d组和CHF 14 d组CVF和LVMI升高更明显(P<0.01),且CHF 14 d组较CHF7d组升高更显著(P<0.05)。CHF1d组、CHF 7 d组和CHF 14 d组CTGF mRNA及蛋白表达均明显高于假手术组(P<0.01),各CHF组CTGFmRNA及蛋白表达比较,差异有统计学意义(P<0.05,P<0.01)。结论 CTGF可能参与大鼠压力负荷性心肌肥厚的发生和发展,且与CHF的严重程度密切相关。

Objective To investigate the relation between expression of connective tissue growth factor（CTGF） and myocardial fibrosis in rats with chronic heart failure（CHF） induced by pressure overload. Methods Eight of 45 male Wistar rats were taken as sham-operated group, and other rats were used to establish（CHF） model by suprarenal aortic constriction, then the model rats were randomly divided into three groups：CHF 1 day,7 days and 14 days. The collagen volume fraction（CVF） and left ventricular mass index（LVMI） were determined in all groups. The morphology of myocardium was studied with HE and Masson staining. Expression of CTGF mRNA and protein were evaluated by RT-PCR and Western blot respectively. Results Compared with sham group rats,the CVF and LVMI in CHF 1 d group,CHF 7 d group and CHF 14 d group rats were obviously increased （P 〈 0.01）. Compared with CHF 1 d group rats, the CVF and LVMI in CHF 7 d group and CHF 14 d group rats were obviously increased （P 〈 0.01）. The CVF and LVMI in CHF 14 d group increased singnificantly compared with CHF 7 d group （P 〈0.05）. The expression of CTGF in the left ventricular myoeardium was significantly increased at different stages of CHF compared with sham operation group （P 〈 0.01）. Conclusion CTGF may be involved in the development of myocardial hypertrophy in rats induced by pressure overload,and its level is related closely to the severity of CHF.