PARP-1 inhibitor reduces inflammation and oxidative stress in rats with chronic obstructive pulmonary disease by activating SIRT1-PGC-1α axis
10.3969/j.issn.1000-484X.2023.12.014
- VernacularTitle:PARP-1抑制剂通过激活SIRT1-PGC-1α轴减轻慢性阻塞性肺疾病大鼠的炎症和氧化应激反应
- Author:
Yaru HOU
1
;
Xinle SHU
;
Xia ZHANG
;
Sen LI
;
Wenmu YONG
Author Information
1. 汉中市中心医院,汉中 723000
- Keywords:
PARP-1;
Chronic obstructive pulmonary disease;
SIRT1;
PGC-1α
- From:
Chinese Journal of Immunology
2023;39(12):2540-2544
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To establish an experimental model of chronic obstructive pulmonary disease(COPD)in rats,and explore whether polyadenosine diphosphate ribose polymerase-1(PARP-1)inhibitors regulate Sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γ co-activator 1α(PGC-1α)to reduce inflammation and oxidative stress in COPD rats,and explore the possibility of SIRT1-PGC-1α axis as a new target of PARP-1 inhibitor.Methods:Twelve of 48 SD rats were randomly selected as healthy group,and the remaining rats were used to construct experimental models of COPD.Rats that were successfully modeled were randomly divided into model group,PARP-1 inhibitor treatment group and PARP-1 inhibitor+PGC-1α inhibitor group.HE staining was used to observe pathological changes of lung tissue,ELISA was used to detect levels of TNF-α,IL-6,IL-1β,malondialdehyde(MDA),superoxide dismutase(SOD)in rats lung tissue,fluorescence quantitative PCR was used to detect expression levels of SIRT1 and PGC-1α mRNA of rats in each group,Western blot was used to detect expressions of SIRT1 and PGC-1α proteins.Results:Lung tissue structure of rats in healthy group was complete,compared with healthy group,lung tissue of model group suffered structural damage,with a large number of inflammatory cells infiltrated,contents of TNF-α,IL-1β and IL-6 in alveolar lavage fluid were significantly increased,con-tent of MDA in serum was significantly increased,while content of SOD was significantly reduced,and expressions of SIRT1,PGC-1α mRNA and protein were significantly reduced;compared with model group,lung tissue structure of rats in PARP-1 inhibitor treatment group was recovered,and inflammatory cells were reduced,contents of TNF-α,IL-1β and IL-6 were significantly reduced,content of MDA in serum was significantly reduced,while content of SOD was significantly increased,and expressions of SIRT1,PGC-1α mRNA and protein were significantly increased;compared with PARP-1 inhibitor treatment group,the number of inflammatory cells in PARP-1 inhibitor+PGC-1α inhibitor group was increased,contents of TNF-α,IL-1β and IL-6 were significantly increased,content of MDA in serum was significantly increased,while content of SOD was significantly reduced,expressions of SIRT1,PGC-1α mRNA and protein were significantly reduced.Conclusion:PARP-1 inhibitors can alleviate inflammation and oxidative stress by activating SIRT1-PGC-1α axis,thereby effectively alleviating COPD.
