【摘要】 目的:探究硫化氢（H₂S）在低氧诱导的肺动脉高压（PAH）大鼠中的作用。方法:将45只健康SD大鼠随机分为三组:对照组、模型组、治疗组。模型组和治疗组在氧浓度为（10±0.5）%的环境下每日处理8 h,连续处理4周,对照组在常氧环境下饲养;治疗组在处理结束后通过腹腔注射50μmol/kg NaHS溶液,每日一次,连续处理4周。实验结束后,测量各组大鼠平均肺动脉压力（mPAP）、右心室收缩压（RVSP）以及右心室肥厚指数[RV/（LV+S）],苏木精-伊红（HE）染色观察组织形态学变化,免疫荧光染色检测组织中α-平滑肌肌动蛋白（α-SMA）表达,免疫组织化学染色检测组织中诱导型一氧化氮合酶（iNOS）表达,实时荧光定量PCR检测组织中M1型巨噬细胞标志物TNF-α、白细胞介素6（IL-6）、iNOS与M2型巨噬细胞标志物甘露糖受体C2（Mrc2）、巨噬细胞半乳糖N-酰基半乳糖胺特异性凝集素1（Mgl1）、精氨酸酶-1（Arg1）的mRNA表达水平。结果:与对照组比较,模型组大鼠mPAP、RVSP显著增高（P<0.05）,RV/（LV+S）显著增加（P<0.05）,组织有明显炎症细胞浸润,肺动脉管壁厚度显著增高（P<0.05）,α-SMA和iNOS表达显著增加（P<0.05）,TNF-α、IL-6、iNOS的mRNA表达水平显著升高（P<0.05）,而Mrc2、Mgl1、Arg1的mRNA表达水平显著下降（P<0.05）;与模型组比较,治疗组大鼠mPAP、RVSP显著降低（P<0.05）,RV/（LV+S）显著下降（P<0.05）,炎症细胞浸润减少,肺动脉管壁增厚显著减轻（P<0.05）,α-SMA和iNOS表达显著下降（P<0.05）,同时,TNF-α、IL-6、iNOS的mRNA表达水平显著下降（P<0.05）,Mrc2、Mgl1、Arg1的mRNA表达水平显著升高（P<0.05）。结论:硫化氢可能通过促进巨噬细胞向Ⅱ型巨噬细胞分化,进而减轻肺动脉高压大鼠的肺动脉血管重构。更多还原

【Abstract】 Objective: To explore the role of hydrogen sulfide in hypoxia-induced pulmonary arterial hypertension（PAH） rats. Methods: 45 healthy SD rats were randomly divided into 3 groups: control group, model group, and treatment group. The model group and the treatment group were treated for 8 hours a day in an environment with an oxygen concentration of（10±0.5）% for 4 weeks, and the control group was reared in a normoxic environment; After the treatment, the treatment group was intraperitoneally injected with 50 μmol·kg^-1 NaHS solution once a day for 4 consecutive weeks. After the experiment, the mean pulmonary artery pressure（mPAP）, right ventricle systolic pressure（RVSP） and right ventricular hypertrophy index [RV/（LV+S）] of each group were measured. HE staining to observe tissue morphological changes, Immunofluorescence staining was used to detect the expression of α-smooth muscle actin（α-SMA） in the tissue, Immunohistochemical staining was used to detect the expression of induced nitrogen monoxide synthase（iNOS） in tissues, Real-time fluorescent quantitative PCR was used to detect the mRNA expression levels of M1 macrophage markers（TNF-α, IL-6, iNOS） and M2 macrophage markers（Mrc2, Mgl1, Arg1） in tissues. Results: Compared with the control group, the mPAP and RVSP of the model group increased significantly（P<0.05）, RV/（LV+S） increased significantly（P<0.05）, the tissues had obvious inflammatory cell infiltration, and the pulmonary artery wall thickness increased significantly（P<0.05）, the expression of α-SMA and iNOS increased significantly（P<0.05）, the mRNA expression levels of TNF-α, IL-6 and iNOS increased significantly（P<0.05）, while the mRNA expression levels of Mrc2, Mgl1, Arg1 decreased significantly（P<0.05）; Compared with the model group, mPAP and RVSP in the treatment group were significantly reduced（P<0.05）, RV/（LV+S） was significantly reduced（P<0.05）, inflammatory cell infiltration was reduced, and pulmonary artery wall thickening was significantly reduced（P<0.05）, the expression of α-SMA and iNOS decreased significantly（P<0.05）. At the same time, the mRNA expression levels of TNF-α, IL-6, iNOS decreased significantly（P<0.05）, and the mRNA expression levels of Mrc2, Mgl1 and Arg1 were significant increase（P<0.05）. Conclusions: Hydrogen sulfide may promote the differentiation of macrophages into type II macrophages, thereby reducing pulmonary artery remodeling in rats with pulmonary hypertension.更多还原