硫化氢对低氧性肺动脉高压大鼠肺动脉增殖细胞核抗原及Bcl-2的调节作用

目的　探讨硫化氢 (H2 S)对低氧性肺动脉高压 (HPH)大鼠肺动脉结构重建和肺动脉平滑肌细胞增殖、凋亡的调节作用。方法　选取体重 180～ 2 0 0g的健康雄性Wistar大鼠 2 4只 ,随机分为常氧组、低氧组、低氧 硫氢化钠 (NaHS)组。监测其血液动力学变化及肺动脉结构重建 ,采用免疫组织化学方法检测增殖细胞核抗原 (PCNA)和Bcl 2凋亡蛋白表达 ,并对肺动脉平滑肌细胞增殖与凋亡进行定位和半定量分析。结果　低氧组大鼠平均肺动脉压 (mPAP)明显升高 (P <0 .0 1) ,右室 / (左室 室间隔 )比值显著增加 (P <0 .0 1) ,肺动脉相对中膜厚度 (RMT)和相对中膜面积 (RMA)增加 (P均 <0 .0 1) ;NaHS可明显降低肺动脉压力及抑制肺动脉重建 (P <0 .0 1)。低氧组大鼠肺小动脉平滑肌细胞PCNA和Bcl 2凋亡蛋白表达分别较对照组增高 (P <0 .0 1) ;NaHS可明显下调肺小动脉平滑肌细胞PCNA和Bcl 2蛋白表达 (P <0 .0 1)。结论　新型气体信号分子H2 S可降低肺动脉压力 ,抑制肺动脉平滑肌细胞增殖 ,在HPH及肺血管结构重建的形成中发挥重要作用

The regulatory effect of hydrogen sulfide on pulmonary artery proliferating cell nuclear antigen and Bcl-2 in hypoxic pulmonary hypertensive rats

Objective To explore the regulatory effects of hyd ro gen sulfide (H 2S) on hypoxic pulmonary hypertension and pulmonary vascular rem odeling in rats. Methods Twenty-four rats were divided into 3 groups: control group(n=8), hypoxia group(n=8), and hypoxia NaHS group( n=8). After 21 days of hypoxia, the mean pulmonary artery pressure (mPAP) wa s measured. The weight ratio of right ventricle. left ventricle septum (R/L S r atio) was measured. The microstructure and ultrastrcture changes in pulmonary sm all arteries were examined. The contents of proliferating cell nuclear antigen (PCNA) and Bc l-2 protein expressions were detected by immunohistochemical assay.Resu lts Compared with rats in the control group, the mPAP increased by 45.6 % (P<0.01) and the R/L S ratio increased by 41 % (P<0.01)in hypo xia group, respectively. The relative medium thickness (RMT) and relative medium areas (RMA)under optical microscope increased by 41 % and 49 %, respectively ( P<0.01). The ultrastructure of the pulmonary small arteries also changed sig nificantly. The mPAP and the R/L S ratio of rats in hypoxia NaHS group decreased by 31.2 % and 24 %, respectively compared with those of hypoxia group (P<0. 01). The RMT and RMA in rats of hypoxia NaHS group decreased by 36 % and 31 %, respectively (P<0.01). The expressing integral scores of PCNA and Bcl- 2 protein were significantly higher in the hypoxia group than those of another two groups (P<0.01). NaHS inhibited the expression of PCNA and Bcl-2 prote in respectively(P<0.01).Conclusion H 2S has important modu lating effects on pulmonary hypertension and pulmonary vascular structural remod eling.