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Gentiopicroside promotes autophagy to alleviate nonalcoholic steatohepatitis in rats via up⁃regulating the expression of LC3Ⅱ
Received date: 2023-03-14
Online published: 2023-09-26
Objective To clarify the effect of gentiopicroside on alleviating nonalcoholic steatohepatitis (NASH) in rats, and to explore the role of LC3II gene and autophagy in this process. Methods Establishment of SD rat NASH model was established and assigned to normal control group, model control group, gentiopicroside group, gentiopicroside+autophagy inhibitor 3-methyladenine group, metformin positive control group, 8 rats in each group. After 4 weeks of treatment, mRNA and protein expression of LC3Ⅱ were detected, LC3Ⅰ in liver tissue was assessed by q-PCR and Western blot, HE staining was performed for liver histopathology, the therapeutic effect of gentiopicroside on NASH in rats was evaluated with serum lipids (CHOL and TG), alanine aminotransferase and inflammatory factor (IL-1β and TNF-α) changes. Results (1)In the normal control group, the structure of hepatic lobule was normal, without fatty change and inflammatory damage; In the model control group, the structure of hepatocyte cord was disordered, with severe liver steatosis and inflammatory damage, and spot and flaky necrosis was observed; The liver steatosis and inflammatory damage were alleviated in gentiopicroside group and metformin positive control group; Compared with gentiopicroside group, liver steatosis and inflammatory damage in gentiopicroside+3?MA group were significantly aggravated, and the structure of hepatic lobule was disordered and necrosis was increased. (2)The ALT, CHOL, TG, IL-1β, TNF-α levels of NASH model control group were significantly higher than those in the normal control group, the ALT, CHOL, TG, IL-1β, TNF-α levels of gentiopicroside group, metformin positive control group were reversed to some extent, while gentiopicroside+3?MA group the level of ALT, CHOL, TG, IL-1β, TNF-α is higher than that of gentiopicroside group, the difference was statistically significant, all P < 0.05. (3)The expression of LC3Ⅱ mRNA and protein in the liver tissue of rats in the model control group was significantly lower than that in the normal control group. This trend was reversed in the gentiopicroside group and the metformin positive control group, while the expression of LC3ⅡmRNA and protein in the gentiopicroside+3-MA group was significantly lower, the difference was statistically significant, all P < 0.05. Conclusion Gentiopicroside could alleviate NASH-related liver injury in rats. Its mechanism may be related to GPS up-regulating the expression of LC3Ⅱ in liver tissue and promoting autophagy
Jie DING , Siqi LIU , Yiying WANG , Lin WANG , Chenghong SHI , Fang WANG , Guoji CHANG , Lijuan HUA , Huayi CHEN , Shenghao LI , Qingqing. WANG . Gentiopicroside promotes autophagy to alleviate nonalcoholic steatohepatitis in rats via up⁃regulating the expression of LC3Ⅱ[J]. The Journal of Practical Medicine, 2023 , 39(16) : 2022 -2028 . DOI: 10.3969/j.issn.1006-5725.2023.16.003
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