8-甲氧补骨脂素对对乙酰氨基酚致小鼠急性肝损伤的保护作用

Protective Effect of 8-Methoxypsoralen against Acetaminophen-induced Acute Hepatic Injury in Mice

目的研究8-甲氧补骨脂素(8-methoxypsoralen,8-MOP)对对乙酰氨基酚(acetaminophen,APAP)致小鼠急性肝损伤的保护作用。方法采用对乙酰氨基酚所致小鼠急性肝损伤模型。24 h后,检测小鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和乳酸脱氢酶(LDH);留取肝脏组织,常规石蜡包埋切片,HE染色,光镜观察肝脏组织病理变化;制备肝匀浆,测定肝中还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)和丙二醛(MDA)的含量。结果与正常对照组比较,模型组小鼠血清中ALT、AST和LDH活性明显升高,肝脏组织出现明显的肝细胞变性坏死;与模型组相比,8-甲氧补骨脂素可以明显降低小鼠血清中ALT、AST和LDH的活性,降低肝组织中MDA的含量,升高GSH/GSSG比值,肝组织病理损伤也明显减轻。结论 8-甲氧补骨脂素对对乙酰氨基酚致小鼠急性肝损伤具有明显的保护作用。

OBJECTIVE To investigate the hepatoprotective effect of 8-methoxypsoralen against acetaminophen-induced acute hepatic injury in mice. METHODS Liver injury model of mice was induced by subcutaneous injection of acetaminophen. Twenty-four hours later, the activities of serum alanine aminotransferase（ALT）, aspartate aminotransferase（AST） and lactate dehydroge- nase （LDH） were determined, and the liver tissues were collected for histopathological assessment by HE staining under light microscope. The ratio of glutathione（GSH） and oxidized glutathione（GSSG）, and the content of GSH, GSSG and malondialdehyde （MDA） in liver homogenate were also measured. RESULTS Compared with the normal control group, the model group could markedly increase serum ALT, AST and LDH activities, and the degeneration and necrosis could be observed in liver tissues. Compared with the model group, 8-methoxypsoralen could markedly decrease serum ALT, AST and LDH activities, reduce the MDA level in liver homogenate, and increase GSH content and the ratio of GSH/GSSG in the liver homogenate. The hepatic histopathological changes in liver were also significantly ameliorated. CONCLUSION The 8-methoxypsoralen can prevent the liver from acetaminophen-induced acute hepatic injury.