中国中药杂志

2020, v.45(16) 3915-3921

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鬼针草水煎液对高脂高糖诱导的小鼠非酒精性脂肪肝的作用及机制研究
Effect and mechanism of Bidens pilosa decoction on non-alcoholic fatty liver induced by high fat and high glucose in mice

高晓乐;段冷昕;仇可可;郭曼琳;焦叶林;王冬梅;
GAO Xiao-le;DUAN Leng-xin;QIU Ke-ke;GUO Man-lin;JIAO Ye-lin;WANG Dong-mei;Medical School, Henan University of Science and Technology;

摘要(Abstract):

该研究旨在探讨鬼针草水煎液对高脂高糖诱导的小鼠非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)的作用及相关作用机制。Balb/c小鼠随机分为正常组、模型组、二甲双胍(200 mg·kg~(-1))组、鬼针草水煎液(10 g·kg~(-1))组和二甲双胍(100 mg·kg~(-1))+鬼针草水煎液(5 g·kg~(-1))联合组。除正常组外,其他4组给予高脂高糖饲料8周,建立非酒精性脂肪肝模型,随后治疗4周,眼球取血,处死取材,检测相关指标。结果显示,与模型组相比,各给药组血脂血糖水平均明显降低(P<0.05);HE染色结果表明各给药组的肝组织病理损伤显著改善;油红O染色结果显示各给药组脂肪分布显著减少(P<0.01);免疫组织化学染色结果显示各给药组的肝组织葡萄糖调节蛋白78(GRP78)蛋白表达量明显降低(P<0.01);Western blot结果显示给药组内质网应激信号通路相关因子GRP78、磷酸化蛋白激酶R样内质网激酶(p-PERK)、真核翻译起始因子2α(eIF2α)、上调激活转录因子4(ATF4)、C/EBP同源蛋白(Chop)、肌醇需求因子1α(IRE1α)和剪切的含半胱氨酸的天冬氨酸氨基转移酶(cleaved-caspase-12)的蛋白表达水平明显降低(P<0.01);联合组结果优于单独给药组。该研究表明鬼针草水煎液对高脂高糖所致小鼠非酒精性脂肪肝具有显著的治疗作用,其机制可能与下调内质网应激相关因子的表达,减轻内质网应激所致肝细胞凋亡,下调血脂血糖水平有关。
This study aimed to investigate the effect and possible mechanism of Bidens pilosa decoction on non-alcoholic fatty liver disease(NAFLD) induced by high fat and high glucose in mice. Bald/c mice were randomly divided into normal group, model group, metformin(200 mg·kg~(-1)) treatment group, Bidens pilosa decoction(10 g·kg~(-1)) treatment group, metformin and B. pilosa decoction(100 mg·kg~(-1)+5 g·kg~(-1)) treatment group. Except for the normal group, mice in the other four groups were fed with high-fat and high-glucose diet for 8 weeks to establish the non-alcoholic fatty liver model. After 4 weeks of treatment, blood was collected from the eyeballs, the mice were sacrificed, and relevant indicators were detected. The results showed that compared with the model group, blood lipid and blood glucose levels of each treatment group were significantly lower(P<0.05); HE staining results showed that liver pathological damage in each treatment group was significantly improved; oil red O staining results showed fat distribution in each treatment group significantly reduced(P<0.01); immunohistochemical staining showed that glucose regulated the protein expression of protein 78(GRP78) in liver tissues of each treatment group was also significantly reduced(P<0.01); Western blot results showed that endoplasmic reticulum stress signal pathway-related factors GRP78, phosphorylated-protein kinase R-like ER kinase(p-PERK), eukaryotic translation-initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), C/EBP homologous protein(Chop), inositol requiring 1α(IRE1α), and cleaved-cysteinyl aspartate specific proteinase 12(cleaved-caspase-12) were significantly reduced(P<0.01). The results of the combined drug treatment group were better than those of the single drug treatment group. These results showed that B. pilosa decoction had the effect in improving non-alcoholic fatty liver, and its mechanism may be related to the down-regulation of the expression of endoplasmic reticulum stress(ERS)-related factors, and the reduction of the apoptosis of hepatocytes caused by ERS and the down-regulation of blood lipid and blood glucose levels.

关键词(KeyWords): 鬼针草水煎液;二甲双胍;高脂高糖;非酒精性脂肪肝;内质网应激
Bidens pilosa decoction;metformin;high fat and high glucose;non-alcoholic fatty liver(NAFLD);endoplasmic reticulum stress(ERS)

Abstract:

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基金项目(Foundation): 国家自然科学基金项目(81601225)

作者(Author): 高晓乐;段冷昕;仇可可;郭曼琳;焦叶林;王冬梅;
GAO Xiao-le;DUAN Leng-xin;QIU Ke-ke;GUO Man-lin;JIAO Ye-lin;WANG Dong-mei;Medical School, Henan University of Science and Technology;

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