瞬时受体电位香草酸亚型1通道蛋白在心肌梗死后修复和重构中的作用

The Protective Role of Transient Receptor Potential Vanilloid Subtype 1 in Post Myocardial Infarction Healing and Remodeling

目的:研究瞬时受体电位香草酸亚型1通道蛋白(TRPV1)在心肌梗死(心梗)后修复和重构中的保护作用。方法:在TRPV1基因敲除(TRPV1-/-)小鼠和野生型(WT)小鼠左冠状动脉结扎建立心梗模型后分为TRPV1-/-心梗组、野生型心梗组;假手术组分为TRPV1-/-假手术组、野生型假手术组,监测心梗后第7天的死亡率、梗死面积。免疫组化检测成肌纤维细胞渗透和胶原成分沉积,超声心动图检测左心室重构和心功能,用酶联免疫吸附法(ELISA)测定组织转化生长因子(TGF)-β1、血管内皮生长因子和基质金属蛋白酶-2的表达水平,Western blot测定Smad2的表达。结果:心梗后第7天,TRPV1-/-心梗组的死亡率高于野生型心梗组(P<0.05),TRPV1-/-心梗组梗死面积大于野生型心梗组(P<0.001)。TRPV1-/-心梗组与野生型心梗组比较,TRPV1-/-小鼠的成肌纤维细胞渗透明显增多,胶原成分沉积增加,差异有统计学意义(P均<0.05)。TRPV1-/-心梗组比野生型心梗组左心室重构加重,心功能恶化,转化生长因子、血管内皮生长因子和基质金属蛋白酶-2的表达水平增高(P均<0.05),磷酸化Smad2蛋白明显升高,差异均有统计学意义(P<0.05)。结论:TRPV1缺失可能通过增强TGF-β-Smad2蛋白信号通路的表达而损害心梗后修复,加重左心室重构,死亡率增加,表明TRPV1在心梗后的修复和重构中起了保护性的作用。

Objective：To investigate the protective role of transient receptor potential vanilloid subtype 1 （TRPV1）in post myocardial infarction（MI） healing and remodeling. Methods ：TRPVI-null mutant（TRPV1^-/-） mice and wild-type（WT） mice were subjected to left anterior descending branch ligation to create MI model and the corresponding sham operation control. 7 days after MI, the mortality rate and infarct size were measured. The infiltration of myofibroblasts and the deposition of collagen were examined by immunohistochemistry, the remodeling of left ventricle and cardiac function were detected by eachocardiogram;the levels of transforming growth factor（ TGF）-β1 ;the vascular endothelial growth factor（ VEGF）, and matrix metalloproteinase （MMP）-2 were examined by ELISA;Smad2 was deteded by Western blot analysis. Results ：7 days after MI, TRPV1^-/- mice showed increased mortality rate than WT mice （36% vs 16% , P 〈 0. 05 ）accompanied with increased infarct size（ P 〈 0. 001 ）. Compared with WT mice, the infiltration of myofibroblasts and the deposition of collagen were increased in TRPV1^-/- mice （P 〈 0.05 respectively）. Echocardiogram showed increased end-systolic diameter and end-diastolic diameter with reduced ejection fraction in TRPV1^-/- mice compared than WT mice（P 〈 0. 001 ）. ELISA analysis presented upregulated expression of TGF-β1, VEGF,and MMP-2 in TRPV1^-/- mice than that in WT mice（P 〈 0. 01 respectively）. Western blot indicated enhanced Smad2 expression in TRPV1^-/- mice compared with WT mice（ P 〈 0. 05 ）. Conclusion：The ablation of TRPV1 could markedly impair the post infarction healing and increase the rate of MI mortality. This might be because of the enhancement of TGF-β-Smad2 signaling and therefore revealing the possible protective role of TRPV1 in MI healing.