培哚普利对TAA诱导大鼠肝纤维化NOX4/NLRP3 信号通路的影响

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中图分类号：R575.2 文献标志码：A DOI：10.11958/20252146

The effect perindopril on NOX4/NLRP3 signaling pathway in TAA-induced liverfibrosis inrats

Hudagula’，MA Zhenhua²△，LU Yan³，DUANChunlan²，LI Kai1

1Sol，otouedicalCoge，nerogoliaUesityiencendchnlogyotouna;

2，3，FstAfltedColege， Corresponding Author E -mail： mazhenhua912@sina.com

Abstract：ObjectiveTo investigateefect perindopril onnicotinamideadenine dinucleotide phosphate （NADPH）oxidase4（NOX4）/NOD-like receptor protein3（NLRP3） signaling pathway inrat liver fibrosis induced by thioacetamide（TAA）.MethodsThirty-two SDrats were romlydivided into blank group， model group （TAA 200 mg/kg， twice a week for 6 weeks） low/high dose group （TAA + perindopril 2/8mg/kg ）， with 8 rats in each group. Two weeks after modeling，administration group was given correspondingdoseperindoprilbygavage（for4 weeks）. Atend6thweek，liverpathologicalsectionswere used toobservepathologicalchanges ivertissuedeges fibrosis inflammation.The biochemical analyzer wasused to detect alanineaminotransferase（ALT）aspartate aminotransferase （AST）.Enzyme-linked immunosorbent assy （ELISA）wasused to detect NLRP3 IL- 1β Immunohistochemistry was used to detect NOX4，NLRP3， Caspase -1 ，IL- 1β protein α -smooth muscle agonist protein （ α -SMA）.ResultsCompared with blank group，livercollagen fibers were significantlyproliferated inmodel group， alarge number inflammatory cells infiltrated，serumlevelsALTAST，as wellasNLRP3 IL- ⋅1β in rats were significantly increased.Theaverage optical densityvalues positive proteins suchas NOX4，NLRP3，Caspase-1，IL-1β α -SMA in rat liver tissue increased significantly P<0.05 ）.Compared with model group， proliferation collagen fibersinflammatoryinfiltrationweresignificantlyreducedinbothlow-dosehigh-dosegroups，serumlevels ALT AST，NLRP3 IL- ⋅1β in rats were significantly decreased.The average optical density values positive proteins such as NOX4，NLRP3， Caspase- -1 ，IL- 1β α-SMA in rat liver tissue decreased significantly （ P<0.05 ） Moreover， degree liver fibrosis reduction inrats was beter in high-dosegroupthan thatin low-dose group. ConclusionPerindopril mayregulate NLRP3 signaling pathwaybyinhibiting expresson NOX4，reby reducing oxidative stress damage inflammatory responses thus delaying process liver fibrosis.

KeyWords：hepatic fibrosis；perindopril;NADPHoxidase4;NLRfamily，pyrindomain-containing3protein; oxidative stress; inflammation

肝纤维化是慢性肝病发展过程中常见的病理改变，其发生机制与慢性炎症和细胞外基质（ECM）蛋白的过度沉积密切相关1。（剩余11974字）