摘要
目的探讨内质网应激蛋白CHOP、Caspase-12在异烟肼所致药物性肝损伤大鼠肝组织中的表达变化及其与肝损害的关系。方法 60只Wister大鼠,雌雄各半,随机分为对照(NG)组、异烟肼模型(INH)组,每组30只,模型组以100mg/kg异烟肼每天灌胃1次,连续灌胃3、7、10、14和21 d,对照组灌胃生理盐水。测定肝脏指数;检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST);HE染色观察肝脏病理形态;TUNEL检测凋亡细胞;Western blot检测CHOP、Caspase-12的表达。结果连续给予异烟肼后大鼠血清ALT、AST明显高于对照组(F=39.19,F=10.02,均P<0.01);凋亡细胞增加;肝组织中CHOP、Caspase-12表达上调,差异有统计学意义(F=42.32,F=40.25,均P<0.01)。结论异烟肼引发的肝损伤与CHOP、Caspase-12表达上调导致内质网介导的肝细胞凋亡增加有关,但内质网应激凋亡通路活化参与药物性肝损伤的程度还需进一步研究探讨。
Objective To investigate the expression of endoplasmic reticulum stress(ERS) proteins, CHOP and Caspase-12, on isoniazid-induced liver injury in rats and the relationship between thous two proteins’ expression and liver injury. Methods Sixty Wistar rats were randomly divided into normal group and INH-model group, with 30 rats in each group. INH-model group was given isoniazid solution (100mg/kg body weight) once a day and normal group was given saline instead, both of them were intervene for 3 days, 7 days, 10 days, 14 days and 21 days. The liver index of rats was detected by weighing method. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by automatic biochemical analyzer. Liver pathological morphology was observed by HE stain. Apoptotic cells were detected by TUNEL assay. The expression of protein CHOP and Caspase-12 was detected by Western blot. Results ALT and AST of model group are both higher than those of normal group ( F =39.19, F =10.02, both of them P <0.01). Apoptotic cells of model group is more than that of normal group. The expression of CHOP and Caspase-12 in model group is up-regulation, which is higher than INH-model group’s expression ( F =42.32, F =40.25, both of them P <0.01). Conclusion Liver injury induced by isoniazid is related to increased apoptosis of hepatocytes which is mediated ER via CHOP and Caspase-12 up-regulation. And the degree of ERS apoptotic pathway activation influence for drug-induced liver injury needs further study.
作者
彭馨仪
罗新华
Peng xinyi;Luo xinhua(Guizhou Medical University, Guiyang 550025, Guizhou, China;Department of infectious disease, Guizhou provincial people’s hospotal, Guiyang 550002, Guizhou, China)
出处
《贵州医药》
CAS
2019年第2期174-177,共4页
Guizhou Medical Journal
关键词
药物性肝损伤
内质网应激
异烟肼
细胞凋亡
Drug-induced liver injury
Endoplasmic reticulum stress
Isoniazid
Apoptosis
