卡托普利对压力负荷增加大鼠心肌促纤维化细胞因子的影响

目的观察卡托普利对压力负荷增加大鼠心肌促纤维化细胞因子转化生长因子-β1(TGF-β1)和结缔组织生长因子(CT-GF)表达水平的影响。方法采用腹主动脉缩窄术制备压力负荷增加心肌纤维化模型,随机分成3组:假手术组(Sham组)、模型组(Model组)和卡托普利组(Captopril组),每组8只。术后4 w成功造模并开始给药,疗程为4 w。8 w后观察各组心脏质量指数和左心室质量指数、HE染色法观察左室心肌病理学、Masson染色法观察左心室心肌胶原形态,图像分析测量胶原容积分数(CVF)和血管周围胶原面积(PVCA),ELISA法检测心肌羟脯氨酸含量以及免疫组化法测定左室心肌TGF-β1和CTGF的表达。结果与Sham组比较,Model组大鼠心脏质量指数和左心室质量指数均明显升高(P0.01);与Model组比较,Captopril组则均显著降低(P0.01)。(2)与Sham组比较,Model组大鼠CVF、PVCA和羟脯氨酸含量均明显升高(P0.01);与Model组比较,Captopril组则均显著降低(P0.01)。(3)与Sham组比较,Model组大鼠心肌组织TGF-β1、CTGF表达均显著升高(P0.01);与Model组比较,Captopril组则均显著降低(P0.01)。结论卡托普利具有逆转心肌纤维化的作用,可能与抑制心肌组织促纤维化细胞因子TGF-β1、CTGF表达有关。

Effect of Captopril on myocardial fibrogenic cytokines in rats with pressure overload

Objective To observe the effect of Captopril on the expression of myocardial fibrogenic cytokine transforming growth factor-β1（TGF-β1） and connective tissue growth factor（CTGF）.Methods Sixteen Sprague-Dawley（SD） rats induced by the abdominal aorta constriction preparation were randomly assigned into Model group and Captopril group（n = 8）（Captopril group,100 mg.kg-1.d-1）.Age matched SD sham operated group（n = 8） as control.The model of pressure overload-induced myocardial fibrosis was successfully established after 4 weeks of operation.After four weeks of Captopril treatment,heart mass index and left ventricular mass index were measured,left ventricular myocardial pathology was detected by HE staining,left ventricular myocardial collagen forms by Masson staining,collagen volume fraction（CVF） and perivascular collagen area（PVCA） by Image-pro Plus Version 6.0 software,in concurrent evaluation of myocardial hydroxyproline content by ELISA,as well as left ventricular myocardial TGF-β1 and CTGF expression by immunohistochemical staining.Results Compared with Sham group,heart mass index and left ventricular mass index were significantly increased in Model group（P 0.01）;Compared with Model group,Captopril had significantly decreased these indexes（P 0.01）.Compared with Sham group,CVF and PVCA and myocardial hydroxyproline content were significantly increased in Model group（P 0.01）;Compered with Model group,Captopril reduced these indexes significantly（P 0.01）.Compared with Sham group,myocardial tissue of CTGF and TGFβ1 protein content were increased in Model group（P 0.01）;Compared with Model group,Captopril had significantly reduced the expression of CTGF and TGF-β1（P 0.01）.Conclusion Captopril had the effect on regressing myocardial fibrosis by inhibition of myocardial tissue fibrogenic cytokine TGF-β1 and CTGF expression.