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乙醇预处理通过抑制补体系统激活减少肝 I/R 损伤。

Ethanol preconditioning reduces hepatic I/R injury by inhibiting the complement system activation.

机构信息

Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China.

出版信息

J Surg Res. 2011 Apr;166(2):314-23. doi: 10.1016/j.jss.2009.05.037. Epub 2009 Jun 18.

DOI:10.1016/j.jss.2009.05.037
PMID:19854450
Abstract

BACKGROUND

Ethanol preconditioning (EtOH-PC) refers to a phenomenon in which cerebral, intestinal, and myocardial tissues are protected from the deleterious effects of ischemia/reperfusion (I/R) by prior ingestion of ethanol at low to moderate levels. Whether EtOH-PC can offer protective effects against hepatic I/R injury and whether these effects are associated with inhibition of complement activation were investigated.

METHODS

Male SD rats were divided into four groups, i.e., sham operation, ethanol control, IR, and ethanol-pretreatment I/R (EIR) groups. EtOH-PC was induced by gavaging rats with 40% ethanol at a dose of 5 g/kg body weight 24 h prior to experiment. Animal survival rate was compared. Liver function, hepatic MDA level, plasma complement C3 level, and serum hemolytic activity were determined. Histologic changes and complement C3 deposition in liver section were examined. Expression of liver complement 3 mRNA was analyzed by quantitative real-time -PCR.

RESULTS

The 14-d survival rates were remarkably higher in the EIR groups than in the corresponding IR groups when hepatic ischemia time was 110, 120, and 130 min. Serum ALT, AST, IL-1β, and liver tissue MDA were significantly lower, and histopathologic changes significantly milder in the EIR group than in the IR group (P <0.05). Compared with the IR group, both the reduction in CH50 and plasma C3 were significantly suppressed, and the staining of C3 in liver tissue significantly reduced in the EIR group. There were no significant differences of hepatic C3 mRNA among four groups.

CONCLUSIONS

Ethanol preconditioning reduces hepatic I/R injury, and the effect is associated with inhibition of complement activation.

摘要

背景

乙醇预处理(EtOH-PC)是指在低至中等水平摄入乙醇后,大脑、肠道和心肌组织免受缺血/再灌注(I/R)的有害影响的现象。研究了 EtOH-PC 是否可以提供对肝 I/R 损伤的保护作用,以及这些作用是否与抑制补体激活有关。

方法

雄性 SD 大鼠分为四组,即假手术、乙醇对照、IR 和乙醇预处理 I/R(EIR)组。在实验前 24 小时,通过灌胃大鼠 40%乙醇以 5 g/kg 体重的剂量诱导 EtOH-PC。比较动物存活率。测定肝功能、肝 MDA 水平、血浆补体 C3 水平和血清溶血活性。检查肝组织切片中的组织学变化和补体 C3 沉积。通过定量实时 PCR 分析肝补体 3 mRNA 的表达。

结果

当肝缺血时间为 110、120 和 130 分钟时,EIR 组的 14 天存活率明显高于相应的 IR 组。EIR 组血清 ALT、AST、IL-1β和肝组织 MDA 明显低于 IR 组,组织病理学变化明显较轻(P<0.05)。与 IR 组相比,EIR 组 CH50 和血浆 C3 的减少均明显受到抑制,肝组织中 C3 的染色明显减少。四组肝 C3 mRNA 无明显差异。

结论

乙醇预处理可减轻肝 I/R 损伤,其作用与抑制补体激活有关。

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