平卧菊三七对二乙基亚硝胺诱导小鼠肝脏损伤的影响

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

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-αmRNA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。

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 5groups（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-αand AP-2in liver tissues were detected.Paraffin-embedded liver tissues were used for HE 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-αmRNA level（10-to 4-fold of control）,AP-2 mRNA level（295 % to 138 % of control）,TUNEL apoptotic index（6.3 % to1.1 %）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-αexpression.