高血压大鼠左室重构时Toll样受体4的表达及作用

Expression and function of Toll-like receptor 4 (TLR4) in hypertensive left ventricular remodeling

目的探讨Toll样受体4（toll like receptor 4，TLR4）在高血压大鼠左室重构中的表达及作用。方法健康雄性sprague—dawley（SD）大鼠6～8周龄，体重160～190g。采用两肾一夹法建立Coldblatt鼠模型，45只SD大鼠随机分为高血压组（25只）和假手术组（20只）。每周测1次尾动脉压，每两周测1次超声心动图。术后第8周，应用RT—PCR及Western—blot从mRNA及蛋白水平检测左室心肌TLR4的表达情况；放免法检测血管紧张素Ⅱ（AngⅡ）的含量。结果与假手术组相比，术后8周高血压组尾动脉压、收缩末期经线室壁应力（Meridional end—systolic wall stress，MESS）及左室重量指数（left ventricle mass index，LVMI）、相对室壁厚度（relative wall thickness，RWT）和心肌AngⅡ含量均明显增高（P〈0．01）；高血压组大鼠左室心肌组织中TLR4 mRNA及蛋白表达水平也明显升高（P〈0．01）。相关性分析TLR4蛋白表达与LVMI、RWT呈正相关；同时与动脉压、MESS及局部AngⅡ含量相关。结论高血压左室重构时TLR4表达明显增高，表明TLR4及其介导的免疫、炎症反应可能参与高血压左室重构的发生发展，持续的压力负荷及心肌局部AngⅡ含量可能对左室心肌TLR4表达起到重要调节作用。

Objective To investigate the expression and function of Toll-like receptor 4 （TLR4） in hypertensive left ventricular remodeling. Methods The Goldblatt model of two-kidney one-clip （2K1 C） renovascular hypertension was induced in forty-five male Sprague-Dawley rats. They were randomly divided into hypertension group （ group H, n = 25 ） and sham operation group （group C, n = 20）. The caudal arterial pressure was measured once a week and echocardiogram was examined every two weeks. The concentration of AngⅡ in left ventricle was measured by radioimmunoassay, and western blotting and RT-PCR were used to examine the mRNA and protein expression of TLR4 in the left ventricle eight weeks after operation. Results Compared with group C, the caudal arterial pressure, meridional end-systolic wall stress （MESS）, left ventricle mass index （LVMI）, relative wall thickness （RWT） and the concentration of Ang Ⅱ were significantly increased in group H eight weeks after operation （P 〈 0. 01 ）. TLR4 mRNA and protein expression in the left ventricle were obviously higher in group H （P 〈 0. 01 ）. Positive correlations were observed between the protein expression of TLR4 and LVMI, RWT. Conclusion The expression of TLR4 is significantly increased in hypertensive left ventricular remodeling. Enhanced expression of TLR4 and its mediated immunoinflammatory reactions contribute to the development of hypertensive left ventricular remodeling. Sustained pressure overload and the concentration of Ang Ⅱ may induce the expression of TLR4 in left ventricle.