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Kangtaizhi Granule Alleviated Nonalcoholic Fatty Liver Disease in High-Fat Diet-Fed Rats and HepG2 Cells via AMPK/mTOR Signaling Pathway.
Journal of Immunology Research ( IF 3.5 ) Pub Date : 2020-08-20 , DOI: 10.1155/2020/3413186
Jiaxin Zhang 1 , Haixia Du 1 , Menglan Shen 2 , Zhengqi Zhao 1 , Xinmiao Ye 1
Affiliation  

Kangtaizhi granule (KTZG) is a Chinese medicine compound prescription and has been proven to be effective in nonalcoholic fatty liver disease (NAFLD) treatment clinically. However, the underlying mechanisms under this efficacy are rather elusive. In the present study, network pharmacology and HPLC analysis were performed to identify the chemicals of KTZG and related target pathways for NAFLD treatment. Network pharmacology screened 42 compounds and 79 related targets related to NAFLD; HPLC analysis also confirmed six compounds in KTZG. Further experiments were also performed. In an in vivo study, SD rats were randomly divided into five groups: control (rats fed with normal diet), NAFLD (rats fed with high-fat diet), and KTZG 0.75, 1.5, and 3 groups (NAFLD rats treated with KTZG 0.75, 1.5, and 3 g/kg, respectively). Serum lipids were biochemically determined; hepatic steatosis and lipid accumulation were evaluated with HE and oil red O staining. In an in vitro study, HepG2 cells were incubated with 1 mM FFA to induce lipid accumulation with or without KTZG treatment. MTT assay, intracellular TG level, oil red O staining, and glucose uptake in cells were detected. Western blotting and immunohistochemical and immunofluorescence staining were also performed to determine the expression of lipid-related genes PPAR-γ, SREBP-1, p-AKT, FAS, and SIRT1 and genes in the AMPK/mTOR signaling pathway. In high-fat diet-fed rats, KTZG treatment significantly improved liver organ index and serum lipid contents of TG, TC, LDL-C, HDL-C, ALT, and AST significantly; HE and oil red O staining also showed that KTZG alleviated hepatic steatosis and liver lipid accumulation. In FFA-treated HepG2 cells, KTZG treatment decreased the intracellular TG levels, lipid accumulation, and attenuated glucose uptake significantly. More importantly, lipid-related genes PPAR-γ, SREBP-1, p-AKT, FAS, and SIRT1 expressions were ameliorated with KTZG treatment in high-fat diet-fed rats and FFA-induced HepG2 cells. The p-AMPK and p-mTOR expressions in the AMPK/mTOR signaling pathway were also modified with KTZG treatment in high-fat diet-fed rats and HepG2 cells. These results indicated that KTZG effectively ameliorated lipid accumulation and hepatic steatosis to prevent NAFLD in high-fat diet-fed rats and FFA-induced HepG2 cells, and this effect was associated with the AMPK/mTOR signaling pathway. Our results suggested that KTZG might be a potential therapeutic agent for the prevention of NAFLD.

中文翻译:

康泰止颗粒通过AMPK / mTOR信号通路减轻了高脂饮食喂养大鼠和HepG2细胞的非酒精性脂肪肝疾病。

康泰止冲剂(KTZG)是一种中药复方,已被证明在临床上可有效治疗非酒精性脂肪性肝病(NAFLD)。但是,在这种功效下的潜在机制相当难以捉摸。在本研究中,进行网络药理学和HPLC分析以鉴定KTZG的化学物质和NAFLD治疗的相关靶途径。网络药理学筛选了42种与NAFLD有关的化合物和79种相关靶标;HPLC分析还确定了KTZG中有6种化合物。还进行了进一步的实验。在体内研究中,SD大鼠随机分为五组:对照组(正常饮食喂养的大鼠),NAFLD(高脂饮食喂养的大鼠)和KTZG 0.75、1.5和3组(用KTZG 0.75、1.5,和3 g / kg)。血清脂质通过生化测定;用HE和油红O染色评价肝脂肪变性和脂质蓄积。在一项体外研究中,将HepG2细胞与1 mM FFA孵育,以诱导脂质蓄积,无论是否进行KTZG处理。检测MTT,细胞内TG水平,油红O染色和细胞中葡萄糖的摄取。还进行了免疫印迹,免疫组化和免疫荧光染色,以确定脂质相关基因PPAR- γ的表达。,SREBP-1,p-AKT,FAS和SIRT1以及AMPK / mTOR信号通路中的基因。在高脂饮食喂养的大鼠中,KTZG治疗显着改善了肝脏器官指数,并显着改善了TG,TC,LDL-C,HDL-C,ALT和AST的血脂含量;HE和油红O染色也显示KTZG减轻了肝脂肪变性和肝脂质蓄积。在FFA处理的HepG2细胞中,KTZG处理显着降低了细胞内TG水平,脂质积累和葡萄糖吸收。更重要的是,脂质相关基因PPAR- γ在高脂饮食喂养的大鼠和FFA诱导的HepG2细胞中,KTZG处理可改善SREBP-1,p-AKT,FAS和SIRT1的表达。在高脂饮食喂养的大鼠和HepG2细胞中,也通过KTZG处理修饰了AMPK / mTOR信号通路中的p-AMPK和p-mTOR表达。这些结果表明,KTZG有效地改善了高脂饮食喂养的大鼠和FFA诱导的HepG2细胞的脂质蓄积和肝脂肪变性,从而预防了NAFLD,并且这种作用与AMPK / mTOR信号通路有关。我们的结果表明,KTZG可能是预防NAFLD的潜在治疗剂。
更新日期:2020-08-20
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