摘要
目的:观察苦参素对衣霉素诱导的小鼠急性肝损伤的保护作用。方法:将昆明种小鼠分为正常组、衣霉素模型组、硫普罗宁对照组、苦参素低、中、高剂量组(40、80、160 mg/kg),每组10只。以1 mg/kg衣霉素灌胃造模,测定血清中的丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)的水平,以及肝脏组织中的丙二醛(MDA)含量和还原型谷胱甘肽(GSH)的活性。观察肝脏组织病理学变化,采用免疫组化技术观察苦参素对衣霉素诱导的急性肝损伤小鼠肝脏GRP78分布的影响,使用酶联免疫吸附剂(ELISA)测定急性肝损伤小鼠血清GRP78水平,使用Td T介导d UTP缺口末端标记法(TUNEL)检测肝脏组织细胞凋亡。结果:苦参素中、高剂量组ALT、AST的活性和肝组织中GSH、MDA的水平与模型组相比均具有统计学差异(P<0.05或P<0.01);肝脏病理切片显示苦参素各剂量组肝细胞变性、坏死、炎性细胞浸润程度有改善;免疫组化技术发现肝组织GRP78分布范围依次减小;ELISA法测定苦参素组(40、80、160 mg/kg)能显著降低模型组小鼠血清中GRP78的含量,TUNEL技术发现苦参素各剂量组能抑制衣霉素诱导的急性肝损伤小鼠肝细胞凋亡。结论:苦参素对衣霉素诱导的小鼠急性肝损伤有保护作用,其作用机制可能与抑制内质网应激介导的肝细胞凋亡有关。
AIM: To explore the protective effect of sophora capsule on acute tunicamycin( TM)hepatic injury in mice. METHODS: Kunming mice were randomly divided into normal group, model group,Tiopronin positive control group,Sophora,low,medium and high dose group( 40 mg / kg,80 mg / kg and 160 mg / kg),each group of 10. The TM liver injury model of mice was made by intragastrical administration of 1 mg / kg TM. The serum levels of alanine aminotransferase( ALT), aspartate aminotransferase( AST) were measured. The activities of malondialdehyde( MDA) and the contents of glutathione( GSH) in hepatic tissues were also measured. The pathological changes of liver were observed with microscopy. The result was confirmed with histological examination. Serum levels of glucose-related protein 78( GRP78) were detected using immunohistochemical localization and enzyme linked immunosorbent assay( ELISA). Hepatocyte apoptosis was tested using Td T mediated-d UTP nick end labeling( TUNEL). RESULTS: Sophora( 80 mg / kg,160 mg / kg) significantly decreased serum ALT,AST levels( P〈0. 05 or P〈0. 01) and MDA content in hepatic tissues( P〈0. 05 or P〈0. 01),increased the activities of GSH( P〈0. 05 or P〈0. 01). Sophora repaired liver pathological tissue damage and decreased serum GRP78 levels and liver GRP78 expression by ELISA and TUNEL. CONCLUSION:Sophora has a protective effect on TM-induced liver injury in mice. Its mechanism may be the inhibition of endoplasmic reticulum stress mediated liver cell apoptosis.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2015年第8期882-886,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
安徽中医药大学科研资助计划项目(2012zr004)
关键词
苦参素胶囊
衣霉素
小鼠急性肝损伤
内质网应激
sophora capsule
tunicamycin
a-cute liver injury in mice
endoplasmic reticulum stress