Mechanism of HMGB1-mediated pyroptosis involved in pulmonary vascular remodeling in mice with pulmonary arterial hypertension
10.3969/j.issn.1673-4130.2024.16.012
- VernacularTitle:HMGB1介导细胞焦亡参与肺动脉高压小鼠肺血管重构的机制研究
- Author:
Mingyuan LI
1
;
Leiqi WU
;
Yun WU
Author Information
1. 新疆医科大学第一附属医院全科医学科,新疆乌鲁木齐 830054
- Keywords:
pulmonary arterial hypertension;
high mobility group protein 1;
pyroptosis
- From:
International Journal of Laboratory Medicine
2024;45(16):1979-1985
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of high mobility group protein 1(HMGB1)-mediated pyroptosis involved in pulmonary vascular remodeling in mice with pulmonary arterial hypertension(PAH).Methods Forty SD mice were divided into control group,PAH group,PAH+HMGB1 neutralizing antibody(HMGB1 Ab)group and PAH+necronecroamide(NSA)group.Except the control group,the remaining 3 groups were treated with hypoxia to establish PAH model.PAH+HMGB1 Ab group and PAH+NSA group were treated with HMGB1 Ab and NSA respectively.After the treatment,the mean pulmonary artery pres-sure(mPAP)and right ventricular hypertrophy index(RVHI)of mice in each group were detected.Hema-toxylin-eosin staining was used to observe the pulmonary histopathological changes and calculate the percent-age of pulmonary artery wall thickness(WT)and the percentage of pulmonary artery wall area(WA).The serum levels of interleukin(IL)-1β and IL-18 were detected by enzyme-linked immunosorbent assay.The ex-pression of gasdermin D(GSDMD)in lung tissues of mice in each group was observed by immunohistochemi-cal staining.Real-time fluorescence quantitative PCR and western blot were used to detect the expression of HMGB1,nucleotide-binding oligomerized domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),Cysteinyl aspartate-specific proteinase-1(Caspase-1),and GSDMD in lung tissues of mice in each group.Results Compared with control group[(1.81±0.19)kPa,(0.27±0.03)],mPAP and RVHI in PAH group[(3.97±0.41)kPa,(0.41±0.04)]were significantly increased,and the difference was statistically significant(P＜0.05).Compared with the control group,the pulmonary artery wall of PAH group was significantly thickened,and the vascular smooth muscle cells proliferated and hypertrophy.The de-gree of pulmonary artery wall thickening in PAH+HMGB1Ab and PAH+NSA groups was significantly re-duced compared with PAH group.WT and WA in PAH group[(42.06±4.38)％,(50.56±5.24)％]were sig-nificantly higher than those in control group[(23.64±2.46)％,(25.12±2.63)％],the difference was statisti-cally significant(P＜0.05).Compared with control group[(23.56±2.48)pg/mL,(22.68±2.32)pg/mL],se-rum levels of IL-1β and IL-18 in PAH group[(94.51±9.62)pg/mL,(58.21±5.97)pg/mL]were significant-ly increased,and the difference was statistically significant(P＜0.05).Compared with PAH group[(48.57±5.02)％],the positive rate of GSDMD in PAH+HMGB1Ab and PAH+NSA groups[(16.52±1.76)％,(14.62±1.59)％[was significantly decreased,and the difference was statistically significant(P＜0.05).The protein expression of HMGB1,NLRP3,ASC,Caspase-1 and GSDMD in lung tissues of PAH group were sig-nificantly higher than those of control group(P＜0.05).Conclusion HMGB1 neutralizing antibody can in-hibit pyroptosis of PAH mice,thereby reducing pulmonary artery pressure and improving pulmonary vascular remodeling.
