| 吴 宾,张 婧,卫 玮,蔡冰冰,张 阳,袁 铭,杨自更.PHB2抑制低氧性肺动脉高压小鼠右心室重塑的作用[J].,2024,(1):25-30 |
| 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 |
| 投稿时间：2023-08-01 修订日期：2023-08-24 |
| DOI：10.13241/j.cnki.pmb.2024.01.005 |
| 中文关键词: 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3 |
| 英文关键词: Prohibitin 2 Hypoxia-induced pulmonary hypertension Ventricular remodeling Signal transduction and activator of transcription 3 |
| 基金项目:新疆维吾尔族自治区自然科学基金项目（2022D01C644）；新疆军区总医院喀喇昆仑基金项目（2022JC002） |
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| 中文摘要: |
| 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-α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。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the effects of prohibitin 2 on right ventricular remodeling in hypoxia-induced pulmonary hypertension (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, oxidative 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 of PHB2 expression 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-1β, IL-6 and TNF-α and increased SOD and GSH-Px in right ventricular tissue (P<0.05), and the levels of PHB2 expression 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. |
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