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目的:探讨肾组织葡萄糖调节蛋白78、94(GRP78、94)和Toll样受体4(TLR4)的表达及其在肝肾综合征发生中的作用。方法:采用胆总管结扎诱导肝硬化及肝肾综合征大鼠模型(BDL组),术后1、2、4和6周各选6只大鼠取血及组织标本。从股静脉取血,监测血浆丙氨酸转氨酶(ALT)、总胆红素(TBil)、尿素氮(BUN)、肌酐(Cr)。用ELISA检测血浆肿瘤坏死因子-α(TNF-α)含量。取肝、肾组织称其质量,并制备标本;用逆转录-聚合酶链反应(RT-PCR)、蛋白质Westernblot分别检测肾组织GRP78、94和TLR4的mRNA及蛋白表达。同时以假手术组设为对照(C组)。结果:与C组比较,BDL组各时间点大鼠肝脏、肾脏质量及血浆ALT、TBil和血浆TNF-α均明显升高(P<0.05),4周和6周BUN和Cr也明显升高(P<0.05)。BDL组各时间点肾组织GRP78、94mRNA及其蛋白表达均明显低于C组(P<0.01),而TLR4mRNA及其蛋白表达量却明显高于C组(P<0.01)。结论:肾组织GRP78、94表达减少可能有助于TLR4炎性信号通路激活,并可能与肝硬化并发的肝肾综合征发生相关。
AIM: To investigate the expression of glucose regulatory proteins 78, 94 (GRP78, 94) and Toll-like receptor 4 (TLR4) in renal tissues and their roles in the development of hepatorenal syndrome. Methods: The rat model of liver cirrhosis and hepatorenal syndrome induced by common bile duct ligation (BDL group) was established. Blood and tissue samples were collected from 1, 2, 4 and 6 weeks after operation. Blood was drawn from the femoral vein and plasma ALT, TBil, BUN and Cr were monitored. Plasma levels of tumor necrosis factor-α (TNF-α) were measured by ELISA. The liver and kidney tissues were weighed and the specimens were prepared. The mRNA and protein expressions of GRP78, 94 and TLR4 in renal tissues were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. At the same time as the sham operation group as a control (C group). RESULTS: Compared with group C, the liver and kidney weights, plasma ALT, TBil and plasma TNF-α were significantly increased in BDL group at each time point (P <0.05), and the levels of BUN and Cr were significantly increased at 4 and 6 weeks (P <0.05). The expression of GRP78,94 mRNA and protein in renal tissues in BDL group were significantly lower than those in C group (P <0.01), while the expression of TLR4 mRNA and protein was significantly higher in group B than that in group C (P <0.01). Conclusion: The decrease of GRP78,94 expression in renal tissue may contribute to the activation of TLR4 inflammatory signaling pathway, and may be related to the occurrence of hepatorenal syndrome complicated with cirrhosis.