平卧菊三七对二乙基亚硝胺诱导小鼠肝脏损伤的影响

目的:探讨平卧菊三七茎提取物(Ethanol extraction from Gynura Procumbens stem,EEGS)对二乙基亚硝胺(Diethylnirtosamine,DEN)诱导小鼠化学性肝损伤的保护作用。方法:40只昆明雄性小鼠,随机分为5组(每组8只):空白对照组、给药对照组、DEN模型组、EEGS治疗组(50 mg·kg^-1和200 mg·kg^-1),模型及治疗组每周经口给予165 mg·kg^-1 DEN,8周后停止DEN处理,成模之后,治疗组及给药对照组每天灌胃相应剂量的EEGS,7 d后处死小鼠。血清用于检测ALT、AST活性;HE、TUNEL和PAS染色分别检测组织病理学、细胞凋亡及糖原水平;RT-PCR检测肝TNF-α、AP-2等基因表达变化。结果:与模型组相比,EEGS(200 mg·kg^-1)能有效降低DEN诱导的血清ALT、AST活性以及TNF-α mRNA和AP-2 mRNA的升高,而对PPAR-γ、HGF mRNA的升高及IL-6 mRNA的降低无明显作用;且能有效减少凋亡细胞数量并抑制糖原增多,明显改善肝实质细胞的减少和脂肪变性等病理变化。结论:EEGS通过下调TNF-α,抑制炎症、细胞凋亡,阻止肝脏脂肪化,减轻DEN引起的化学性肝损伤。

Effects of Gynura Procumbens(Lour.) Merr on diethylnirtosamine induced liver injury in mice

OBJECTIVE To investigated effects of an ethanol extraction from Gynura Procumbens (Lour.) Merr stem (EEGS) on diethylnirtosamine (DEN)-induced liver injury in mice. METHODS Kunming mice were randomly divided into 5 groups (8 animals in each group):control group, EEGS only group, DEN model group and DEN+ EEGS treatment groups. DEN (165 mg·kg^-1) per week was taken orally for 8 weeks to induce hepatic damage. Mice in DEN+ EEGS treatment groups received oral EEGS (50 or 200 mg·kg^-1·d^-1) for 7 d. Serum ALT, AST and mRNA expressions of TNF-α and AP-2 in liver tissues were detected. Paraffin-embedded liver tissues were used for H&E staining, TUNEL staining and PAS staining. RESULTS EEGS at dose of 200 mg·kg^-1·d^-1 reduced elevation of DEN-induced ALT (239% to 135% of control), TNF-α mRNA level (10-to 4-fold of control), AP-2 mRNA level (295% to 138% of control), TUNEL apoptotic index (6.3% to 1.1%) and content of hepatic glycogen. Both hepatocyte loss and steatosis induced by DEN were also significantly resorted after EEGS treatment.CONCLUSION EEGS exerts inhibitory effects on DEN-induced liver damage (including inflammation, apoptosis and steatosis) in mice through down-regulation of TNF-α expression.