结缔组织生长因子与肾血管性高血压大鼠心肌纤维化的关系研究

目的:探讨结缔组织生长因子(CTGF)在高血压心肌纤维化发生、发展中的作用。方法:以两肾一夹肾血管性高血压大鼠(RHR)为模型,假手术实验大鼠(SOR)为对照,将实验大鼠分为4组:高血压4周组(H4),高血压12周组(H12),假手术4周组(S4),假手术12周组(S12)。用免疫组化法对CTGF、TGFβ1在4组的左室心肌的分布及表达进行半定量分析;用VG染色法观察左室心肌胶原形态,图像分析系统测量胶原容积分数(CVF)和血管周围胶原面积(PVCA)。结果:(1)CVF、PVCA在RHR组明显高于SOR组(P均<0.01);(2)CTGF、TGFβ1在RHR组左室心肌中的表达较SOR组明显增强(P均<0.05),CTGF主要在血管平滑肌和心肌间质及疤痕组织中表达。SOR组CTGF在心肌间质呈弱表达;(3)相关分析表明,CTGF与TGFβ1(r=0.626,P<0.05)、CVF(r=0.815,P<0.01)、PVCA(r=0.793,P=0.01)呈正相关。结论:CTGF参与了肾血管性高血压心肌纤维化的形成过程。

Relation between CTGF and Myocardial Fibrosis in Renovascular Hypertensive Rats

Objective: To investigate roles of the connective tissue growth factor (CTGF) in the development of myocardial fibrosis in renovascular hypertensive rats. Methods: Renovascular hypertensive rat models were established. The experimental rats were divided into four groups: hypertensive and sham|operated groups for four weeks, and hypertensive and sham-operated groups for twelve weeks. CTGF and TGF-β 1 were evaluated by immunohistochemical staining in the fourth and the twelfth week after operation to explore their distribution and expression in the left ventricular tissue. The VanGieson staining was used for determining total collagen in the left ventricular interstitial tissue. Results: Compared with that in sham operated rats(SOR), the collagen volume fraction (CVF),perivascular collagen area (PVCA),the expression of CTGF and TGF-β 1 in the ventricular tissue were significantly increased in renovascular hypertensive rats (P<0.01 and P<0.05, respectively). The expression of CTGF was primarily in myocardial interstitium and artery intimal while the expression of TGF-β 1 mainly in myocardial cells. The correlation analysis revealed that the expression of CTGF positively correlated with that of TGF-β 1(r = 0.626, P< 0.05),CVF(r=0.815, P<0.01) and PVCA(r=0.793,P<0.01). Conclusion: The connective tissue growth factor may play important roles in the development of myocardial interstitial fibrosis.