内毒素预适应减轻急性肝功能衰竭中热休克蛋白27的作用

目的研究热休克蛋白27（HSP27）介导内毒素（LPS）预适应减轻急性肝功能衰竭（ALF）的作用机制。方法实验动物为雄性C57BL/6小鼠。将小鼠分为5组,对照组为正常C57BL/6小鼠;肝功能衰竭组小鼠以LPS10μg/kg＋D-半乳糖胺700 mg/kg,用1 mL0.9%氯化钠溶液溶解后腹腔内注射,建立急性肝功能衰竭的模型;LPS预处理组小鼠经LPS预适应24 h后,建立急性肝功能衰竭的模型;HSP27干扰组小鼠和转染对照组小鼠分别以尾静脉注射包装有干扰HSP27表达的短发夹RNA的重组腺病毒以及对照空病毒,成功干扰HSP27表达后,经LPS预处理,建立急性肝功能衰竭模型。通过比较各组ALT和AST水平,评价肝组织病理损伤程度,以及检测肝组织内TNF-α、IL-6mRNA水平,观察HSP27对LPS预适应减轻急性肝功能衰竭的影响。结果 LPS预适应可明显减轻Galn/LPS所致的肝损伤,干扰HSP27的表达后,小鼠血清ALT和AST明显升高,肝组织病理损伤和炎性反应加重（P〈0.05）。下调HSP27的表达水平后,LPS预适应的保护作用几乎完全消失。结论 LPS预适应可以减轻小鼠的急性肝损伤,HSP27在这一效应中发挥重要作用。

The role of heat shock protein 27 in acute liver failure induced by pretreatment with lipopolysaccharide

Objective To investigate the role of heat shock protein 27（HSP27） in acute liver failure induced by pretreatment with lipopolysaccharide.Methods Male C57BL/6 mice were randomly divided into 5 groups：control group（with no treatment）;liver injury group,which were injected intraperitonelly with D-Galn（700 mg/kg） and LPS（10μg/kg） dissolved in 1 mL sterile saline;LPS pretreatment group,which were injected with LPS（10μg/kg）24 hours before D-Galn/LPS treatment;HSP27 interference group,murine HSP27 was interfered by short hairpin RNA and mice were subjected to D-Galn/LPS with LPS pretreatment;Negative control group,which were also injected with vector virus and treated in the same way with HSP27 siRNA group.Serum ALT and AST levels,hepatic histological damages and mRNA levels of pro-inflammatory cytolines（TNF-αand IL-6） were measured.Results LPS pretreatment significantly reduced liver injury induced by D-Galn/LPS.The interference of HSP27 aggravated liver injury,which could be known from the higher levels of ALT and AST（P＆lt;0.05）,as well as the severer histological damage and more expression of TNF-αand IL-6（P＆lt;0.05）.Reducing the expression of HSP27 largely abrogated the protective effects induced by LPS pretreatment.Conclusion LPS pretreatment could protect against acute liver failure through HSP27 dependent pathways.