脂多糖预处理减轻对乙酰氨基酚所致急性肝损伤

Lipopolysaccharides pretreatment reduces acetaminophen-induced acute liver injury in mice

目的建立对乙酰氨基酚(APAP)引起小鼠急性肝损伤动物模型,探讨低剂量脂多糖(LPS)预处理对APAP引起急性肝损伤的作用。方法 1选取ICR雄性小鼠20只,随机分成APAP组和LPS+APAP组。禁食后,APAP组经腹腔注射APAP(300 mg/kg);LPS+APAP组经腹腔注射先给予LPS(50μg/kg),3 h后再给予APAP(300 mg/kg),密切观察小鼠存活状况,72 h后取材,测生化指标,行肝组织HE染色。2ICR雄性小鼠随机分成APAP 0、0.5、6、12、24、72 h组和LPS+APAP 0、0.5、6、12、24、72 h组。禁食后,APAP组腹腔注射APAP(300 mg/kg);LPS+APAP组腹腔注射LPS(50μg/kg),3 h后再经腹腔注射APAP(300 mg/kg),分别在每组对应时点取材。分离血清测丙氨酸氨基转移酶(ALT),用Beutler改良法测肝脏谷胱甘肽(GSH)含量。结果1APAP组给药4 h左右小鼠开始出现死亡情况,72 h存活率为50%;LPS+APAP组72 h内无死亡。2低剂量LPS预处理能降低血清ALT(P<0.05),减少小鼠肝脏坏死情况(P<0.01)。3 APAP组与LPS+APAP组肝脏GSH含量差异无统计学意义。结论低剂量LPS预处理能显著减轻APAP引起的急性肝损伤,这种作用不是通过减弱N-乙酰苯醌亚胺(NAPQI)耗竭GSH而产生的,可能与其激活了机体的免疫应答,抑制了GSH耗竭的下游机制有关。

Objective To establish an animal model of APAP-induced acute liver injury in mice, and investigate the protective effect of acute liver injury caused by APAP on the low-dose LPS pretreatment. Methods ①20 ICR male mice were randomly divided into APAP group and LPS＋APAP group. APAP group was injected APAP （300 mg/kg）;LPS＋APAP group was injected intraperitoneally LPS （50 μg/kg）, 3 h later giving APAP （300 mg/kg） . After administration, the mice survival situation was closely observed, 72 h later, biochemical indicator was measured. ② ICR male mice were randomly divided into APAP 0, 0. 5, 6, 12, 24, 72 h groups and LPS＋APAP 0, 0. 5 , 6, 12, 24, 72 h groups. APAP group was intraperitoneally injected with APAP （300 mg/kg）; LPS＋APAP group was injected with LPS （50 μg/kg） 3 h before APAP （300 mg/kg） . After administration, serum ALT and other indicator were measured at the corresponding time point. Results ① The survival rate of APAP group was 50% within 72 h;while LPS＋APAP group had no deaths. ②Low-dose LPS pretreatment could reduce serum ALT （ P 〈0. 05 ） , reducing liver necrosis （ P 〈0. 01 ） . ③ APAP group and LPS＋APAP group liver GSH content differences were not statistically significant. Conclusion Low-dose LPS pretreatment could significantly reduce the APAP-induced acute liver injury. Low-dose LPS pretreatment could not reduce GSH depletion, it may activate the body ＇s immune response, and inhibit the downstream mechanisms of GSH depletion.