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Engeletin Down-Regulates the PERK-ATF4 Signaling Pathway to Improve the Liver of Hepatocirrhosis Rats |
DAI Ying, DENG Jiong, LU Yijun, et al |
The Sixth People's Hospital of Chengdu, Sichuan Chengdu 610000, China |
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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.
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[1] Olevskaya ER,Dolgushina AI,Tarasov AN,et al.Prognosis factors of survival in patients with liver cirrhosis and portal hypertension[J].Ter Arkh,2019,91(2):67-72. [2] Rajoriya N,Brahmania M,J Feld J.Implications of manganese in chronic acquired hepatocerebral degeneration[J].Ann Hepatol,2019,18(1):274-278. [3] Gaspar R,Rodrigues S,Silva M,et al.Predictive models of mortality and hospital readmission of patients with decompensated liver cirrhosis[J].Dig Liver Dis,2019,51(10):1423-1429. [4] Bai H,Yin H.Engeletin suppresses cervical carcinogenesis in vitro and in vivo by reducing NF-κB-dependent signaling[J].Biochem Biophys Res Commun,2020,526(2):497-504. [5] Tian Q,Wang G,Zhang Y,et al.Engeletin inhibits Lipopolysaccharide/d-galactosamine-induced liver injury in mice through activating PPAR-γ[J].Pharmacol Sci,2019,140(3):218-222. [6] Zhang Y,Liu XW,Wei J,et al.HIIT and MICT attenuate high-fat diet-induced hepatic lipid accumulation and ER stress via the PERK-ATF4-CHOP signaling pathway[J].Physiol Biochem,2022,78(3):641-652. [7] Cheng L,Yang Z,Sun Z,et al.Schizandrin B mitigates rifampicin-induced liver injury by inhibiting endoplasmic reticulum stress[J].Biol Pharm Bull,2020,43(1):145-152. [8] Zhang J,Chen X,Chen H,et al.Engeletin ameliorates pulmonary fibrosis through endoplasmic reticulum stress depending on lnc949-mediated TGF-β1-Smad2/3 and JNK signalling pathways[J].Pharm Biol,2020,58(1):1105-1114. [9] 翟浩宇,曹欢,杨柳,等.血红素加氧酶1(HO-1)修饰的大鼠骨髓间充质干细胞对肝硬化大鼠T淋巴细胞亚群的影响[J].中华微生物学和免疫学杂志,2020,40(6):444-452 [10] Liu H,Li S,Xu Y,et al.Engeletin protects against cerebral ischemia/reperfusion injury by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways[J].Braz Med Biol Res,2021,54(10):11028-11038. [11] Tang BM,Li ZW,Wang ZY.PERK activator CCT020312 prevents inflammation-mediated osteoporosis in the ovariectomized rats[J].Gynecol Endocrinol,2021,37(4):342-348. [12] Barcena-Varela M,Colyn L,Fernandez-Barrena MG.Epigenetic mechanisms in hepatic stellate cell activation during liver fibrosis and carcinogenesis[J].Int Mol Sci,2019,20(10):2507-2522. |
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