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目的:观察Goldblatt大鼠左室重构过程中TLR4表达及其与压力负荷及左室心肌血管紧张素Ⅱ含量的相互关系,探讨TLR4在高血压左室重构发生发展中的作用及参与机制。方法:健康雄性Sprague-Dawley(SD)大鼠7-9周龄,体重165-210 g。采用2肾一夹法建立Goldblatt大鼠模型,45只SD大鼠随机分为高血压组(H组,n=25)和假手术组(Sham组,n=20)。每周测1次尾动脉压,每2周测1次超声心动图,术后第8周,处死大鼠,留取左室心肌组织。免疫组化观察左室心肌TLR4表达,应用RT-PCR及Western blotting从mRNA及蛋白水平检测TLR4的表达情况;放免检测左室心肌AngⅡ的含量。结果:术后8周H组尾动脉压、收缩末期经线室壁应力(MESS)及左室重量指数(LVMI)、相对室壁厚度(RWT)和心肌AngⅡ含量均明显高于sham组(P<0.01);H组大鼠左室心肌组织中TLR4 mRNA及蛋白表达水平均明显高于sham组(P<0.01);免疫组化发现TLR4的表达,H组主要是在心肌细胞膜,尤其2个或2个以上的心肌细胞相邻处有团簇样表达,但也有半数样本的胞浆内有少量表达;正常对照组主要弥漫表达于胞浆内,胞膜的表达极少。相关性分析TLR4蛋白表达与反应左室重构的LVMI、RWT呈正相关(r=0.614,P<0.01;r=0.621,P<0.01);同时与反应压力负荷的尾动脉压、MESS及局部AngⅡ含量相关。结论:Goldblatt大鼠左室重构过程中TLR4 mRNA及蛋白水平均明显增加,增强表达的TLR4主要位于心肌细胞膜,尤其2个或2个以上的心肌细胞相邻处有团簇样表达。提示TLR4这一与免疫炎症密切相关的跨膜信号转导受体及其介导的信号通路可能参与高血压左室重构的发生发展。
OBJECTIVE: To observe the relationship between TLR4 expression and stress load and the content of angiotensin Ⅱ in left ventricular myocardium during left ventricular remodeling in Goldblatt rats, and to explore the role and mechanism of TLR4 in the occurrence and development of left ventricular remodeling in hypertensive rats. Methods: Healthy male Sprague-Dawley (SD) rats were 7-9 weeks old and weighed 165-210 g. Goldblatt rat model was established by two kidney-one-clip method. Forty-five SD rats were randomly divided into hypertensive group (H group, n = 25) and sham operation group (n = 20). Tail arterial pressure was measured once a week, and echocardiography was performed every 2 weeks. After 8 weeks, rats were killed and left ventricular myocardium was taken. The expression of TLR4 in left ventricular myocardium was observed by immunohistochemistry. The expression of TLR4 was detected by RT-PCR and Western blotting. The content of AngⅡ in left ventricular myocardium was detected by radioimmunoassay. Results: At 8 weeks after operation, tail arterial pressure, MESS, LVMI, RWT and Ang Ⅱ in group H were significantly higher than those in sham group (P < 0.01). The mRNA and protein expression of TLR4 in left ventricular myocardium in H group were significantly higher than those in sham group (P <0.01). The expression of TLR4 was found by immunohistochemistry in H group, especially in myocardial cell membrane, especially in 2 or More than two cardiomyocytes adjacent to the cluster-like expression, but there are also half of the sample cytoplasm a small amount of expression; the normal control group was mainly diffusely expressed in the cytoplasm, the expression of minimal membrane. Correlation analysis showed that there was a positive correlation between TLR4 expression and left ventricular remodeling LVMI and RWT (r = 0.614, P <0.01; r = 0.621, P <0.01) Content related. CONCLUSION: The expression of TLR4 mRNA and protein in left ventricular remodeling in Goldblatt rats were significantly increased. The expression of enhanced TLR4 mainly located in the myocardial cell membrane, especially in the adjacent clusters of two or more cardiomyocytes. It is suggested that TLR4, a transmembrane signal transduction receptor closely related to immune inflammation and its signaling pathway, may be involved in the development of left ventricular remodeling in hypertension.