The effect of perindopril on the NOX4/NLRP3 signaling pathway in TAA-induced liver fibrosis in rats
- VernacularTitle:培哚普利对TAA诱导大鼠肝纤维化NOX4/NLRP3信号通路的影响
- Author:
HUDAGULA
1
;
Zhenhua MA
;
Yan LU
;
Chunlan DUAN
;
Kai LI
Author Information
- Publication Type:Journal Article
- Keywords: hepatic fibrosis; perindopril; NADPH oxidase 4; NLR family,pyrin domain-containing 3 protein; oxidative stress; inflammation
- From: Tianjin Medical Journal 2025;53(10):1027-1032
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the effect of perindopril on the nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)/NOD-like receptor protein 3(NLRP3)signaling pathway in rat liver fibrosis induced by thioacetamide(TAA).Methods Thirty-two SD rats were randomly divided into the blank group,the model group(TAA 200 mg/kg,twice a week for 6 weeks)and the low/high dose group(TAA+perindopril 2/8 mg/kg),with 8 rats in each group.Two weeks after modeling,the administration group was given the corresponding dose of perindopril by gavage(for 4 weeks).At the end of the 6th week,liver pathological sections were used to observe pathological changes of liver tissue and degrees of fibrosis and inflammation.The biochemical analyzer was used to detect alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Enzyme-linked immunosorbent assay(ELISA)was used to detect NLRP3 and IL-1β.Immunohistochemistry was used to detect NOX4,NLRP3,Caspase-1,IL-1β protein and α-smooth muscle agonist protein(α-SMA).Results Compared with the blank group,liver collagen fibers were significantly proliferated in the model group,a large number of inflammatory cells infiltrated,and serum levels of ALT and AST,as well as NLRP3 and IL-1β in rats were significantly increased.The average optical density values of positive proteins such as NOX4,NLRP3,Caspase-1,IL-1β and α-SMA in rat liver tissue increased significantly(P<0.05).Compared with the model group,the proliferation of collagen fibers and inflammatory infiltration were significantly reduced in both the low-dose and high-dose groups,and serum levels of ALT and AST,NLRP3 and IL-1β in rats were significantly decreased.The average optical density values of positive proteins such as NOX4,NLRP3,Caspase-1,IL-1β and α-SMA in rat liver tissue decreased significantly(P<0.05).Moreover,the degree of liver fibrosis reduction in rats was better in the high-dose group than that in the low-dose group.Conclusion Perindopril may regulate the NLRP3 signaling pathway by inhibiting the expression of NOX4,thereby reducing oxidative stress damage and inflammatory responses and thus delaying the process of liver fibrosis.
