Yan Chun-gen, Zhu Dong-fang, Wang Feng
Department of Internal Medicine, Hospital affiliated to Medical College, Shaoxing College of Arts and Science, Shaoxing, Zhejiang, China.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2007 Dec;19(12):731-4.
To explore the expressions and roles of renal heat shock protein 72(HSP72) and Toll-like receptor 4(TLR4) during development of hepatorenal syndrome in rat.
Following bile duct ligation (BDL), a biliary cirrhosis and hepatorenal syndrome rat model was reproduced. The blood, the renal and hepatic tissues of the rats were examined at 1, 2, 4 and 6 weeks (6 rats were used in each week) after BDL. Blood was withdrawn from the femoral vein and centrifuged. The plasma concentrations of alanine aminotransferase (ALT), total bilirubin (TBil), blood urea nitrogen (BUN) and creatinine (Cr) were measured, and those of the HSP72 and tumor necrosis factor-alpha (TNF-alpha) were assessed with enzyme linked immunosorbent assay (ELISA). After weighing liver and kidney and expressions of HSP72 and TLR4 in renal tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. All data were compared with control group (C group).
The plasma levels of ALT, TBil at each week and of BUN, Cr at 4 and 6 weeks were increased significantly (all P<0.05). The concentration of plasma HSP72 and the expressions of renal HSP72 mRNA and protein were lower (especially at 4 and 6 weeks, both P<0.01) in BDL rats compared with sham operation rats. But the plasma TNF-alpha levels and renal TLR4 (mRNA and protein) expressions were significantly higher than those of sham operation rats (all P<0.01).
Decreased expression of renal HSP72 may contribute to activate the TLR4- initiating inflammatory signal pathway, attributing partly to the pathogenesis of hepatorenal syndrome in biliary cirrhosis.
探讨大鼠肝肾综合征发生过程中肾热休克蛋白72（HSP72）和Toll样受体4（TLR4）的表达及作用。
通过胆管结扎（BDL）复制胆汁性肝硬化和肝肾综合征大鼠模型。在BDL术后1、2、4和6周（每周6只大鼠）检测大鼠的血液、肾和肝组织。从股静脉取血并离心。测定血浆丙氨酸氨基转移酶（ALT）、总胆红素（TBil）、血尿素氮（BUN）和肌酐（Cr）的浓度，并用酶联免疫吸附测定（ELISA）法评估HSP72和肿瘤坏死因子-α（TNF-α）的浓度。称取肝和肾重量后，用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测肾组织中HSP72和TLR4的表达。所有数据与对照组（C组）比较。
各周的血浆ALT、TBil水平以及4和6周的BUN、Cr水平均显著升高（均P<0.05）。与假手术大鼠相比，BDL大鼠血浆HSP72浓度及肾HSP72 mRNA和蛋白表达较低（尤其是在4和6周，均P<0.01）。但血浆TNF-α水平及肾TLR4（mRNA和蛋白）表达显著高于假手术大鼠（均P<0.01）。
肾HSP72表达降低可能有助于激活TLR4起始的炎症信号通路，这在一定程度上归因于胆汁性肝硬化中肝肾综合征的发病机制。
