BACKGROUND High prevalence of obstructive sleep apnea (OSA) in the pulmonary hypertension (PH) population suggests that chronic intermittent hypoxia (CIH) is an important pathogenic factor of PH. However, the exact mechanism of CIH induced PH is not clear. One of the molecules that plays a key role in regulating pulmonary artery function under hypoxic conditions is superoxide dismutase 2 (SOD2). METHODS Our study utilized heterozygous SOD2-/+ mice firstly in CIH model to explore the exact role of SOD2 in CIH causing PH. Expression of SOD2 was analyzed in CIH model. Echocardiography and pulmonary hypertension were measured in wild type (WT) and SOD2-/+ mice under normal air or CIH condition. Hematoxylin-Eosin (H&E) staining and masson staining were carried out to evaluate pulmonary vascular muscularization and remodeling. Micro-PET scanning of in vivo 99mTc-labelled- MAG3-anti-CD11b was applied to assess CD11b in quantification and localization. Level of nod-like receptor pyrin domain containing 3 (NLRP3) was analyzed by real time PCR and immunohistochemistry (IHC). RESULTS Results showed that SOD2 was down-regulated in OSA/CIH model. Deficiency of SOD2 aggravated CIH induced pulmonary hypertension and pulmonary vascular hypertrophy. CD11b+ cells, especially monocytic myeloid cell line-Ly6C+Ly6G- cells, were increased in the lung, bone marrow and the blood under CIH condition, and down-regulated SOD2 activated NLRP3 in CD11b+ cells. SOD2-deficient-CD11b+ myeloid cells promoted the apoptosis resistance and over-proliferation of human pulmonary artery smooth muscle cells (PASMCs) via up-regulating NLRP3. CONCLUSION CIH induced down-regulating of SOD2 increased pulmonary hypertension and vascular muscularization. It could be one of the mechanism of CIH leading to PH.

中文翻译：

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SOD2通过抑制CD11b +细胞中NLRP3的表达来改善小鼠睡眠呼吸暂停模型中的肺动脉高压。

背景技术肺动脉高压（PH）人群中阻塞性睡眠呼吸暂停（OSA）的高患病率提示慢性间歇性缺氧（CIH）是PH的重要致病因素。但是，CIH诱发PH的确切机制尚不清楚。在低氧条件下，调节肺动脉功能的关键分子之一是超氧化物歧化酶2（SOD2）。方法我们的研究首先在CIH模型中利用杂合SOD2-/ +小鼠来探索SOD2在CIH引起PH中的确切作用。在CIH模型中分析了SOD2的表达。在正常空气或CIH条件下，在野生型（WT）和SOD2-/ +小鼠中测量了超声心动图和肺动脉高压。进行苏木精-伊红（H＆E）染色和Masson染色以评估肺血管肌肉化和重塑。体内99mTc标记的MAG3-抗CD11b的Micro-PET扫描用于评估CD11b的定量和定位。通过实时PCR和免疫组织化学（IHC）分析含有3个点样受体的吡啶结构域（NLRP3）的水平。结果结果表明，SOD2在OSA / CIH模型中被下调。SOD2缺乏会加剧CIH诱发的肺动脉高压和肺血管肥大。在CIH条件下，肺，骨髓和血液中的CD11b +细胞，特别是单核细胞系Ly6C + Ly6G-细胞增加，而CD11b +细胞中SOD2激活的NLRP3下调。SOD2缺陷型CD11b +骨髓细胞通过上调NLRP3促进人肺动脉平滑肌细胞（PASMC）的凋亡抗性和过度增殖。结论CIH诱导SOD2的下调增加了肺动脉高压和血管肌肉化。这可能是CIH导致PH的机制之一。