PHB2抑制低氧性肺动脉高压小鼠右心室重塑的作用
Prohibitin 2 Inhibits Right Ventricular Remodeling in Mice with Hypoxia-induced Pulmonary Hypertension
吴宾 1张婧 2卫玮 3蔡冰冰 1张阳 1袁铭 4杨自更1
作者信息
- 1. 新疆军区总医院核医学科 新疆乌鲁木齐 830000
- 2. 新疆军区总医院营养科 新疆乌鲁木齐 830000
- 3. 新疆军区总医院门诊部 新疆乌鲁木齐 830000
- 4. 空军军医大学西京医院心内科 陕西西安 710032
- 折叠
摘要
目的:探讨抗增殖蛋白2(PHB2)在低氧性肺动脉高压(HPH)诱导的右心室重塑中的作用及可能机制.方法:将普通8周龄的 C57BL/6 小鼠随机分为:对照组(Control)、HPH 组、HPH+空病毒(HPH+vector)组、HPH+过表达 PHB2(HPH+PHB2)组.HPH组、HPH+空病毒组、HPH+过表达PHB2组置于低压低氧人工舱内维持4 w,对照组置于常压常氧环境中维持4 w.实验开始3 w前,尾静脉注射平滑肌特异性PHB2过表达的AAV9腺相关病毒及其对照病毒.评估小鼠右室血流动力学、右室重塑指标、炎症、氧化应激、血管活性物质水平以及肺组织PHB2和p-Stat3蛋白表达.结果:与对照组相比,HPH组和HPH+空病毒组RVSP、RVAW、RVHI显著增加(P＜0.05),而RVID显著降低(P＜0.05),右室CVF显著增加(P＜0.05),血浆ET-1和BNP显著增加(P＜0.05),血浆NO、总NOS和iNOS显著降低(P＜0.05),右心IL-1β、IL-6及TNF-a显著增加(P＜0.05),SOD和GSH-Px显著降低(P＜0.05),肺组织PHB2表达降低(P＜0.05),p-STAT3表达增加(P＜0.05).与HPH组和HPH+空病毒组相比,HPH+过表达PHB2组RVSP、RVAW、RVHI显著降低(P＜0.05),而RVID显著增加(P＜0.05),右室CVF显著降低(P＜0.05),血浆ET-1和BNP显著降低(P＜0.05),血浆 NO、总 NOS 和 iNOS 显著增加(P＜0.05),右心 IL-1β、IL-6 及TNF-α 显著降低(P＜0.05),SOD 和 GSH-Px 显著增加(P＜0.05),肺组织PHB2表达增加(P＜0.05),p-STAT3表达降低(P＜0.05).结论:PHB2可减轻HPH诱发的右心室重塑,其机制可能与PHB2抑制STAT3的磷酸化水平有关.
Abstract
Objective:To explore the effects of prohibitin 2 on right ventricular remodeling in hypoxia-induced pulmonary hyper-tension(HPH)mice and potential mechanisms.Methods:Eight-week-old male mice were randomly allocated to the following 4 groups:control group,HPH group,HPH+vector group and HPH+PHB2 group.HPH group,HPH+vector group and HPH+PHB2 group were placed in low-pressure and low-oxygen artificial chamber,and control group were placed in atmospheric oxygen environment for 4 weeks.Adeno-associated virus serotype 9(AAV9)carrying smooth muscle promoter-driven SM22ap encoding PHB2 and empty vectors were injected via tail vein 3 weeks prior to model construction.Hemodynamics,the level of right ventricle remodeling,inflammation,ox-idative stress and vasoactive substances,and the expression levels of PHB2 and p-STAT3 were determined in mice.Results:Compared with control group,RVSP,RVAW,RVHI and CVP were increased significantly(P＜0.05)and RVID was decreased in HPH group and HPH+vector group(P＜0.05),with upregulated plasma ET-1 and BNP(P＜0.05)and downregulated NO,t-NOS and iNOS(P＜0.05),as well as increased IL-1β,IL-6 and TNF-α and decreased SOD and GSH-Px in right ventricular tissue(P＜0.05),and the levels ofPHB2 expres-sion in the lung tissue were decreased(P＜0.05)and p-STAT3 expression was increased(P＜0.05)in HPH group and HPH+vector group.Compared with HPH group and HPH+vector group,RVSP,RVAW,RVHI and CVP were decreased significantly(P＜0.05)and RVID was increased in HPH+PHB2 group(P＜0.05),with downregulated plasma ET-1 and BNP and upregulated NO,t-NOS and iNOS(P＜0.05),as well as decreased IL-1 β,IL-6 and TNF-α and increased SOD and GSH-Px in right ventricular tissue(P＜0.05),and the levels of PHB2 ex-pression in the lung tissue were increased(P＜0.05)and p-STAT3 expression was decreased(P＜0.05)in HPH+PHB2 group.Conclusion:PHB2 alleviates right ventricular remodeling in HPH mice,which may be related to the inhibition of STAT3 phosphorylation by PHB2 in pulmonary artery smooth muscle.
关键词
抗增殖蛋白2/低氧性肺动脉高压/心室重塑/信号转导与转录激活子3Key words
Prohibitin 2/Hypoxia-induced pulmonary hypertension/Ventricular remodeling/Signal transduction and activator of transcription 3引用本文复制引用
基金项目
新疆维吾尔族自治区自然科学基金(2022D01C644)
新疆军区总医院喀喇昆仑基金(2022JC002)
出版年
2024
NETL
NSTL
万方数据