黄杞苷下调PERK-ATF4信号通路改善肝硬化大鼠肝脏的作用

doi:10.3969/j.issn.1006-6233.2023.05.07

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摘要 目的:探讨黄杞苷(Eng)调节蛋白激酶R样内质网激酶(PERK)-转录激活因子4(ATF4)信号通路对肝硬化(HC)大鼠的肝保护作用。方法:随机选出10只大鼠作为对照组(NC组),其余大鼠构建HC大鼠模型,造模成功后随机平分为HC组、L-Eng组(10mg·kg^-1·d^-1)、M-Eng组(20mg·kg^-1·d^-1)、H-Eng组(40mg·kg^-1·d^-1)、H-Eng+CCT组(40mg·kg^-1·d^-1 Eng+2mg·kg^-1·d^-1 CCT020312),每组10只,持续3周。检测肝功能指标、肝组织病理学变化、α-SMA、Collagen表达以及EMT标志蛋白、PERK-ATF4通路蛋白表达。结果:NC组肝组织结构正常,染色清晰,无纤维化现象;HC组出现大面积坏死现象,大量淋巴细胞浸润,肝索排列杂乱,纤维增生以及假小叶形成;Eng处理后,淋巴细胞浸润现象减少,细胞排列较为整齐,纤维增生现象改善;与NC组比较,HC组Ishak评分、Ishak分期、肝脏指数、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)含量、α-SMA、Collagen水平、Vimentin、PERK、ATF4蛋白水平均显著升高(P<0.05),白蛋白(ALB)、总蛋白(TP)含量、E-cadherin蛋白水平均显著下调(P<0.05);Eng处理后以上指标得到改善,且Eng作用效果呈现剂量依赖性;CCT020312逆转了H-Eng对HC大鼠的有利影响。结论:Eng可能通过调控PERK-ATF4信号通路发挥对HC大鼠的肝保护作用。

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	代莹
	邓炯
	陆逸君
	温旭东

关键词 ：黄杞苷, PERK-ATF4信号通路, 肝硬化

Abstract：Objective: To investigate the liver protective effect of engeletin (Eng) on rats with hepatocirrhosis by regulating protein kinase R-like endoplasmic reticulum kinase (PERK) - activating transcription factor 4 (ATF4) signaling pathway. Methods: 10 rats were randomly selected as the control group (NC group), and the rest of the rats were induced into the HC rat model. After successful modeling, they were randomly divided into HC group, L-Eng group (10mg·kg^-1·d^-1), M-Eng group (20mg·kg^-1·d^-1), H-Eng group (40mg·kg^-1·d^-1), and H-Eng+CCT group (40mg·kg^-1·d^-1 Eng+2 mg·kg^-1·d^-1 CCT020312), 10 rats in each group, lasting for 3 weeks. Detection of liver function indicators, liver histopathological changes α- Expression of SMA, Collagen, EMT marker protein, PERK-ATF4 pathway protein. Results: The NC group had normal liver tissue structure, clear staining and no fibrosis; the HC group showed extensive necrosis, massive lymphocyte infiltration, disorganized liver cords, fibrous hyperplasia and pseudobullet formation; after Eng treatment, lymphocyte infiltration was reduced, cells were more neatly arranged and fibrous hyperplasia improved; compared with the NC group, the HC group showed significantly higher Ishak score, Ishak stage, liver index , alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, α-SMA, Collagen levels, Vimentin, PERK, ATF4 protein levels were significantly increased (P<0.05), and albumin (ALB), total protein (TP) levels, E-cadherin protein levels were significantly downregulated in the HC group compared with the NC group (P<0.05); the above indexes were improved after Eng treatment, and the effect of Eng showed a dose-dependent effect; CCT020312 reversed the favorable effect of H-Eng on HC rats.Conclusion: Engeletin may play a liver protective role in HC rats by regulating PERK-ATF4 signaling pathway.

Key words： Engeletin PERK-ATF4 signal pathway Hepatocirrhosis

基金资助:四川省科技计划项目任务合同书,(编号:2021YJ0198)

引用本文:

代莹, 邓炯, 陆逸君, 温旭东. 黄杞苷下调PERK-ATF4信号通路改善肝硬化大鼠肝脏的作用[J]. 河北医学, 2023, 29(5): 737-742.
DAI Ying, DENG Jiong, LU Yijun, et al. Engeletin Down-Regulates the PERK-ATF4 Signaling Pathway to Improve the Liver of Hepatocirrhosis Rats. HeBei Med, 2023, 29(5): 737-742.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.05.07 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I5/737

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