褪黑素减轻对乙酰氨基酚的急性肝脏毒性

Melatonin alleviates acetaminophen-induced acute hepatotoxicity in mice

目的探讨褪黑素(MT)对对乙酰氨基酚(APAP)引起的急性肝脏毒性的保护作用。方法雄性ICR成年健康小鼠随机分为对照(CON)组、MT组、APAP组和APAP+MT组。APAP组经腹腔注射APAP(300 mg/kg);APAP+MT组经腹腔注射给予不同剂量MT(1.25、5、20 mg/kg),30 min后再经腹腔注射APAP。APAP处理4 h后取血清测血液生化指标丙氨酸转氨酶(ALT),用免疫组化法检测肝脏3-硝基酪氨酸(3-NT)水平,用蛋白印迹法测肝脏JNK磷酸化水平。结果与CON组比较,APAP组肝脏系数和ALT水平显著升高(P<0.01,P<0.05),肝脏JNK磷酸化水平上升(P<0.01),3-NT水平升高,而肝脏还原性谷胱甘肽(GSH)含量下降(P<0.01);MT对抗APAP引起的ALT升高(P<0.05),抑制肝脏JNK磷酸化(P<0.01),而对APAP引起的蛋白硝化和GSH耗竭无明显改善。结论 MT通过抑制APAP引起的JNK磷酸化减弱其急性肝脏毒性作用。

Objective To explore the protective effect of melatonin （MT） on acetaminophen （ APAP）-induced acute hepatotoxicity. Methods Adult male ICR mice were randomly divided into 6 groups ： Control （CON） group, MT group, APAP group, APAP ＋ MT group. All mice except CON were intraperitoneally injected with APAP （300 mg/kg）. In APAP ＋ MT group, mice were intraperitoneally injected with different doses of MT （ 1.25,5, 20 mg/ kg） 30 min before APAP. Mice were killed 4 h after APAP. Serum was collected for measurement of alanine amin-otransferase （ALT）. The expression of hepatic 3-nitrotyrosine （3-NT） was detected by immunohistochemistry. The expression of hepatic pJNK was determined using Western blot. Results Liver coefficient and serum ALT level were significantly increased in APAP-treated mice （P 〈 0.01, P 〈 0.05 ）. The expression of hepatic pJNK and 3- NT were upregulated by APAP （ P 〈 0. 01 ）. Hepatic glutathione （GSH） content was significantly decreased in APAP-treated mice （ P 〈 0. 01 ）. MT significantly alleviated APAP-induced elevation of ALT （P 〈 0.05）. In addition, MT significantly inhibited APAP-induced hepatic JNK phosphorylation （ P 〈 0.01 ）, while it had little effect on APAP-induced hepatic GSH depletion and protein nitration （ P 〉 0. 05 ）. Conclusion MT protects against APAP-induced hepatotoxicity through its inhibition of hepatic JNK phosphorylation.