【摘要】 目的观察两肾一夹(twokidney,oneclip)高血压大鼠肥厚的左室心肌细胞中Toll样受体4(Tolllikereceptor4,TLR4)的表达情况。并且应用NFκB阻断剂PDTC进行干预,观察阻断NFκB以后,TLR4在Goldblatt鼠左室心肌细胞中表达的变化,探讨TLR4与左室肥厚发生的关系及NFκB的活性对TLR4表达的影响。方法雄性SpragueDawley(SD)大鼠40只,随机分为高血压非用药组(H组,n=13)、PDTC治疗组(P组,n=14)和假手术组(C组,n=13)3组。H组和P组采用两肾一夹法建立大鼠高血压模型,C组手术过程同上,但不放置银夹。术后两周开始给药直至术后8周,P组给予PDTC200mg/(kg·d)皮下注射,H组和C组给予等体积的生理盐水。每周监测各组大鼠的尾动脉压。术前及处死前行超声心动图检查。术后8周处死大鼠,留取左室标本并称重。应用免疫组化法观察各组大鼠心肌组织中NFκB的表达情况,应用Westernblot检测TLR4在各组大鼠心肌组织中蛋白的表达情况。结果P组血压及左室重量指数(LVMI)较H组显著降低。H组NFκB的表达明显高于C组,而P组大鼠心肌NFκB的表达明显被抑制。各组TLR4的表达情况与NFκB相一致。结论(1)TLR4和NFκB在Goldblatt鼠左室心肌中的表达水平明显增高。(2)PDTC抑制心肌NFκB表达的同时下调TLR4蛋白水平的表达。(3)TLR4信号通路的活化可能参与Goldblatt鼠心肌肥厚的发生和发展。更多还原

【Abstract】 Objective The expression of Toll like receptor 4 (TLR4) was studied in the hypertrophic left ventricular myocytes in renovascular hypertensive rats (RHR). The effect of PDTC, an inhibitor of NF-κB, on the expression of TLR4 was examined. MethodsForty male Sprague-Dawley rats were randomly divided into untreated hypertension group (H group, n=13), PDTC treatment group (P group, 200 mg/kg·d n=14) and sham operation group (C group, n=13). The 2K1C Goldblatt model of renovascular hypertension was established. The tail cuff blood pressure was measured every week, and echocardiography was performed before operation and death. Eight weeks after operation, the samples of the left ventricular were collected expression of NF-κB in the left ventricle was determined by immunohistochemistry and TLR4 by Western blot. ResultsPDTC significantly decreased blood pressure and LVMI after six weeks of treatment. The positive immunoreactivity of NF-κB and the expression of TLR4 in the hypertrophic cardiomyocytes was more pronounced than in P group and C group (P<0.01). Conclusion(1) The expression of TLR4 and NF-κB was enhanced in the hypertrophic cardiomyocytes of Goldblatt rats. (2) PDTC not only inhibit NF-κB, but also suppress the expression of TLR4. (3) TLR4 signaling pathway may be involved in the development of left ventricular hypertrophy.更多还原