目的：比较内毒素（LPS）耐受和糖原合成酶激酶‐3（GSK‐3）抑制剂LiCl对LPS诱导肝损伤的保护效应。方法选取雄性健康SD大鼠36只，体质量（200±10）g ，分为对照组、LPS耐受组和LiCl处理组，每组12只；LPS耐受组于实验第1、2、3天依次接受0．015、0．030和0．060 mg／kg的LPS腹腔注射，LiCl处理组在相同时间点腹腔注射0．25 mL浓度为2．5 mol／L 的LiCl ，对照组腹腔注射0．25 mL PBS ；预处理结束后每组再按是否接受致死量的LPS（10 mg／kg）攻击而分为LPS（＋）和LPS（－）两个亚组，LPS（＋）亚组大鼠接受10 mg／kg的LPS腹腔注射，LPS（－）亚组接受等体积的PBS腹腔注射，连续观察12 h后麻醉、活杀、取材。观察肝脏大体病变；光镜和电镜观察肝组织病理学改变；定量检测血浆中丙氨酸氨基转移酶（ALT ）、乳酸脱氢酶（LDH）及总胆红素（TB）水平；检测血清中IL‐10及 TNF‐α水平。结果对照组在LPS攻击后肝脏组织损伤明显，肝功能指标ALT、LDH和TB明显升高，血清 TNF‐α和IL‐10升高；LPS和LiCl预处理可改善LPS诱导的肝组织损伤，改善肝功能，抑制TNF‐α升高并上调血清IL‐10。结论大剂量LPS腹腔注射可诱导肝损伤，LPS耐受和GSK‐3抑制剂LiCl具有相似的肝保护效应。%Objective To compare protective effect on lipopolysaccharide (LPS)‐induced liver injury by LPS tolerance with that of glycogen synthase kinase‐3 (GSK‐3) inhibitor LiCl .Methods Thirty‐six male healthy Sprague‐Dawley rats (200 ± 10)g were randomly divided into control group ,LPS tolerance groupand LiCl treatment group ,12 rats in each group;the LPS tolerance group was conducted intraperitoneal injection at 0 .015 ,0 .030 and 0 .060 mg/kg (weight) on the first ,second and third day ;LiCl treat‐ment group was also received intraperitoneal injection 0 .25 mL at 2 .5 mol/L LiCl at the same time point ;the control group was in‐traperitoneally injected PBS 0 .25 mL every day ;after pretreatment ,each group was divided into the LPS(-) and LPS(+ ) sub‐groups on the basis that whether lethal dose LPS(10 mg/kg) was accepted .LPS(+ ) subgroup received 10 mg/kg (weight) LPS in‐traperitoneal injection ,and LPS(-) subgroup took the same volume of PBS intraperitoneal injection .After 12 h continuous obser‐vation ,the rats were anaesthetized ,killed when alive and drawn the materials .Observed general pathological changes of liver;patho‐logical changes were observed under light microscope and electron microscope;then the content of glutamic‐pyruvic transaminase (ALT) ,lactate dehydrogenase (LDH) and total bilirubin(TB) of plasma was detected quantitatively ;the content of IL‐10/TNF‐αin serum was measure .Results After LPS attack ,liver histopathology damage was caused to change ,liver function indicators ALT , LDH and TB of control group increased significantly ,TNF‐α and IL‐10 grew plasma;the damaged changes of liver tissue induced could be improved by LPS and LiCl pretreatmen ,as well as the liver function ,and inhibit the increase of TNF‐αand raise plasma IL‐10 .Conclusion Intraperitoneal injection of LPS at a large dose can induce liver damage ,and LPS tolerance and GSK‐3 inhibitor LiCl have similar liver protection effect .
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