盐诱导高血压大鼠左心室心肌中TNF-α、TGF-β1和MMP-9的表达

Expression of TNF-α,TGF-β1 and MMP-9 in left ventricular muscle at salt-induced hypertensive rats

目的探讨TNF-α、TGF-β1和MMP-9在盐诱导高血压模型大鼠左心室心肌中的表达与心肌间质重构中的作用。方法48只5周龄Wistar大鼠,随机分为正常对照(NC)组、低浓度(LS)组和高浓度(HS)组各16只,分别用蒸馏水、2%或3%氯化钠饲养10周后,尾袖法测尾动脉血压,处死取左心室心肌组织,HE染色观察大鼠心肌细胞形态,免疫组化联合酶联免疫吸附法(enzyme linked immunsorbent assay,ELISA)检测TNF-α、MMP-9和TGF-β1的表达水平,Masson染色观察心肌胶原纤维并计算胶原容积分数(collagen volume fraction,CVF)。结果 (1)LS组成模率为75.00%,病死率为6.25%,HS组成模率为81.25%,病死率为12.50%;(2)与NC组相比,饲养10周后LS组和HS组成模大鼠的收缩压均明显增高,但LS组与HS组间比较无明显差异;(3)LS组与HS组成模型大鼠心肌细胞增生肥大,呈不同程度灶性溶解、颗粒与空泡变性,核增大、分裂、畸形,细胞间隙增宽;(4)与NC组相比,LS组与HS组大鼠左心室心肌组织中TNF-α、MMP-9和TGF-β1蛋白表达显著增多,CVF显著增加。结论高盐诱导高血压大鼠左心室心肌间质胶原增生明显,且与TNF-α、MMP-9和TGF-β1表达水平增高有关,提示TNF-α和TGF-β1可能通过上调MMP-9的表达而参与左心室间质胶原重构。

Purpose To study the effect of tumor necrosis factor-α（ TNF-α）,transforming growth factor-β1（ TGF-β1） and matrix metalloproteinase-9（ MMP-9） in left ventricular myocardial interstitial remodeling in high-salt induced hypertensive rats. Methods Wistar rats were divided into three groups： normal control group（ NC,n = 16 drinking normal-salt water）,low salt group（ LS,n = 16 drinking 2% Na Cl solution） and high salt group（ HS,n = 16 drinking 3% Na Cl solution）. Myocardial morphological and structural changes were observed by hematoxylin-eosin staining（ HE）,myocardial collagen network remodeling was observed and collagen volume fraction（ CVF） was calculated by Masson staining. The levels of TNF-α,TGF-β1 and MMP-9 expression in left ventricle（ LV） were measured by biochemistry and enzymology. The levels of TNF-α / TGF-β1 / MMP-9 in blood were determined by enzyme linked immunsorbent assay（ ELISA）. Results The incidence rate of hypertension was 75. 00%（ 12 /16） in LS group,the incidence rate of hypertension was 81. 25%（ 13 /16） in HS group. Compared to control group,after 10 weeks the systoilc blood pressure（ SBP） of LS group and HS group were increased significantly,but no significant differences between the LS group and HS group. Compared with NC group,there were much more significant cardiac myocyte hypertrophy accompanied with nucleus augmentation,pleomorphism and mitosis in the LS group and HS group. Also,there were spotlysis,granular degeneration and vacuolation in the myocytoplasm at some degree. Compared with NC group,The level of TNF-α,TGF-β1 and MMP-9 in blood,as well as left ventricle（ LV） were increased significantly,so did CVF. Conclusions Left ventricular interstitial collagen hyperplasia witch is related to expression level of TNF-α,TGF-β1 and MMP-9 increase in high salt induced-hypertension rats,suggesting that TNF-α and TGF-β1 may affect the ventricular interstitial collagen remodeling of left ventricle through up-regulating MMP-9 expression.