Mechanism of pirfenidone inhibiting cell pyroptosis and reduceing myocardial fibrosis
10.3969/j.issn.1009-0126.2025.01.021
- VernacularTitle:吡非尼酮抑制细胞焦亡减轻心肌纤维化的机制研究
- Author:
Zifeng HE
1
;
Xiangwei LÜ
;
Yang QIN
;
Weikun ZHAO
;
Liqin CHEN
;
Yuechang LI
;
Yufen LU
Author Information
1. 541001 桂林医学院附属医院综合科医疗保健病区
- Publication Type:Journal Article
- Keywords:
antifibrotic agents;
NLR family,pyrin domain-containing 3 protein;
Caspase 1;
pyropto-sis;
pirfenidone
- From:
Chinese Journal of Geriatric Heart Brain and Vessel Diseases
2025;27(1):94-99
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of pirfenidone on myocardial fibrosis in rats and inves-tigate its underlying mechanism.Methods Twenty-four SD rats were randomly divided into sham-operation group,model group,low-and high-dose pirfenidone groups,with 6 rats in each group.Rat model of myocardial fibrosis was established by injecting isoprenaline into the tail vein,while normal saline was given to the sham operation group.Pirfenidone of 150 and 300 mg/(kg·d)were infused gastrically to the rats of low-and high-dose pirfenidone groups after modeling.Mas-son staining was used to observe the severity of myocardial fibrosis,immunohistochemical assay was employed to detect the expression of Collagen-1,NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome,cysteinyl aspartate-specific protease-1(Caspase-1),and Western blotting was performed to detect the protein levels of Collogen-1 and atrial desmo-plakin D(gasdermin D,GSDMD).Results The model group showed obvious myocardial fibrosis,and elevated expression of Collogen-1,NLRP3,Caspase-1 and GSDMD when compared with the sham operation group(P＜0.05).Low-and high-dose pirfenidone treatment resulted in signifi-cantly reduced myocardial fibrosis and reduced expression of Collogen-1,NLRP3,Caspase-1 and GSDMD[(8.14±1.40)％,(6.56±0.75)％vs(22.15±2.57)％,P＜0.05;0.14±0.03 vs 0.33±0.05,0.42±0.13,P＜0.05;(10.34±1.40)％,(10.33±3.40)％vs(23.22±1.99)％,P＜0.05;(15.67±0.56)％,(17.33±0.78)％vs(22.87±1.92)％,P＜0.05;0.43±0.06,0.46±0.11 vs 0.65±0.03,P＜0.05].Conclusion Pirfenidone inhibits cardiomyocyte pyroptosis and attenuates myocar-dial fibrosis through the NLRP3/Caspase-1/GSDMD signaling axis.
