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

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

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。

Objective To explore the impact of hydrogen sulfide(H 2S) 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 H 2S 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 H 2S[(196±22)μmol/L] of hypoxic group was decreased significantly compared with control group[(294±26)μmol/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)μmol/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)μmol/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 H 2S of hypoxic+NaHS group[(324±33)μmol/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)μmol/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 H 2S was decreased significantly in hypoxic+PPG group[(142±45)μmol/L, P <0 05],and mPAP was increased significantly( P <0 05) With the decrease of H 2S 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)μmol/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 H 2S upregulated CO/HO 1 system in pulmonary arteries of hypoxic rats