低氧性肺动脉高压形成中气体信号分子硫化氢对一氧化碳/血红素加氧酶途径的影响

目的研究新型气体信号分子硫化氢(H2S)在大鼠低氧性肺动脉高压形成中对一氧化碳(CO)/血红素加氧酶(HO1)体系的调节作用,以深入探讨H2S在大鼠低氧性肺动脉高压形成中的病理生理意义。方法将27只大鼠随机分为4组对照组(7只),低氧组(7只),低氧 硫氢化钠(NaHS)组(7只),低氧 炔丙基甘氨酸(PPG)组(6只)。低氧21d后分别测定肺动脉平均压、血浆H2S及CO含量,观察肺动脉平滑肌HO1蛋白及HO1mRNA表达。结果随着低氧性肺动脉高压的形成,血浆H2S的含量显著下降,低氧组[(196±22)μmol/L]与对照组[(294±26)μmol/L]比较差异有显著性(P<005);而CO含量、大、中、小各级肺动脉平滑肌HO1蛋白表达[对照组、低氧组分别为(0313±0020)μmol/L、(0348±0021)μmol/L,066±008、079±008,064±005、077±008,054±005、076±009]及其mRNA表达(对照组、低氧组分别为0573±0148、0813±0052,0532±0131、0831±0043,0473±0102、0819±0032)显著升高(P均<005);外源性给予H2S的供体后,低氧 NaHS组血浆H2S含量[(324±33)μmol/L]显著高于低氧组[(196±22)μmol/L,P<005],肺动脉压显著下降(P<005),且血浆CO含量[(0393±0032)μmol/L]、大、中、小各级肺动脉平滑肌HO1蛋白表达(088±004、089±005、089±006)及mRNA表达(0913±0022、0

The regulation of carbon monoxide/heme oxygenase system by hydrogen sulfide in rats with hypoxic pulmonary hypertension

OBJECTIVE: To explore the impact of hydrogen sulfide (H2S) on the carbon monoxide (CO)/heme oxygenase-1 (HO-1) system in pulmonary artery of hypoxic rats. METHODS: Twenty-seven rats were randomly divided into four groups: hypoxic group (n = 7), hypoxic + NaHS group (n = 7), hypoxic + propargylglycine (PPG) group (n = 6) and control group (n = 7). After 21 days, pulmonary artery mean pressure (mPAP) of each rat was evaluated and the plasma concentration of H2S and CO were measured. The expression of HO-1 in pulmonary arteries of each rat was detected by immunohistochemistry technique. In situ hybridization for HO-1 mRNA in pulmonary arteries was also observed. RESULTS: mPAP was significantly increased in hypoxic rats [(20.5 +/- 2.9) mm Hg] as compared with that of normal controls [(14.8 +/- 3.6) mm Hg, P <0.05]. The plasma H2S[(196+/-22 ) micromol/L] of hypoxic group was decreased significantly compared with control group [(294+/-26) micromol/L, P < 0. 05]. The plasma CO and the expression of HO-1 protein and mRNA in large, medium and small sized pulmonary arteries of hypoxic group [ (0.348 +/- 0.021) micromol/L, 0.79+/-0.08, 0.77+/-0.08, 0.76+/-0.09, 0.813+/-0.052, 0.831+/-0.043, 0.819+/-0.032, respectively] were significantly increased compared to control rats [(0.313+/-0. 020) micromol/L, 0.66+/-0.08, 0.64+/-0.05, 0.54+/-0.05; 0.573 +/- 0.148, 0.532+/-0.131, 0.473+/-0.102, respectively; all P <0.05]. Compared with hypoxic group, the plasma H2S of hypoxic + NaHS group [(324+/-33 ) micromol/L] was significantly increased, and mPAP was decreased significantly (all P < 0.05). Meanwhile, compared with hypoxic group, the plasma concentration of CO [(0.393+/-0.032) micromol/L], the expression of HO-1 protein and mRNA in large, medium and small sized pulmonary arteries were significantly increased in hypoxic + NaHS group (0.88+/-0.04, 0.89 +/- 0.05, 0.89 +/- 0.06; 0.913 +/- 0.022, 0.922 +/- 0.021, 0.933 +/- 0.014, respectively; all P < 0.05). However, compared with hypoxic group, the plasma concentration of H2S was decreased significantly in hypoxic + PPG group [(142 +/- 45) micromol/L, P < 0. 05], and mPAP was increased significantly (P < 0.05). With the decrease of H2S in hypoxic + PPG group, the plasma concentration of CO, the expression of HO-1 protein and mRNA in large, medium and small sized pulmonary arteries were significantly decreased [(0.274 +/- 0.032) micromol/L; 0.54 +/- 0.06, 0.56+/-0.04, 0.39+/-0.06; 0.423 +/- 0.043, 0.418 +/- 0.091, 0.382+/-0.051 respectively; all P <0.05] compared to hypoxic group. CONCLUSION: H2S upregulated CO/HO-1 system in pulmonary arteries of hypoxic rats.