Chen Si-yao, Jin Hong-fang, Sun Yan, Tian Yue, Tang Chao-shu, DU Jun-bao
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Zhonghua Er Ke Za Zhi. 2011 Dec;49(12):890-4.
To explore the impact of sulfur dioxide (SO(2)) on hydrogen sulfide (H(2)S)/cystathionine-γ-lyase (CSE) and H(2)S/mercaptopyruvate sulfurtransferase (MPST) pathways in the pathogenesis of hypoxic pulmonary hypertension.
Thirty-two male Wistar rats were randomly divided into four groups: control group (n = 8), hypoxic group (n = 8), hypoxic + SO(2) group (n = 8) and hypoxic + hydroxamate (HDX) group (n = 8). After 21 days of experiment, the concentration and production of H(2)S in lung tissues were measured respectively for each rat. The protein expression of CSE and MPST in intima and media of small pulmonary arteries in rats was detected with immunohistochemical method.
Compared with control group, the mean pulmonary artery pressure (mPAP) in rats of hypoxic group was increased significantly [(33.38 ± 6.32) mm Hg vs. (16.74 ± 3.81) mm Hg, P < 0.01]. Compared with hypoxic group, the mPAP in rats of hypoxic + SO(2) group was decreased significantly [(29.65 ± 2.53) mm Hg vs. (33.38 ± 6.32) mm Hg, P < 0.01]. However, compared with hypoxic group, the mPAP in rats of hypoxic + HDX group was increased significantly [(39.44 ± 6.26) mm Hg vs. (33.38 ± 6.32) mm Hg, P < 0.01]. Compared with control group, the concentration [(2.02 ± 0.43) µmol/g vs. (3.11 ± 0.42) µmol/g, P < 0.01] and production [(19.64 ± 3.48) nmol/(g·min)vs. (28.20 ± 5.95) nmol/(g·min), P < 0.05] of H(2)S were decreased significantly in rats of hypoxic group, respectively. When treated with SO(2), hypoxic rats showed an increased concentration [(2.73 ± 0.20) µmol/g vs. (2.02 ± 0.43) µmol/g, P < 0.01] and production [(26.24 ± 1.92) nmol/(g·min) vs. (19.64 ± 3.48) nmol/(g·min), P < 0.01] of H(2)S in lung tissue compared with those without receiving SO(2) treatment. When treated with HDX, hypoxic rats showed a significant decrease in concentration [(1.64 ± 0.23) µmol/g vs. (2.02 ± 0.43) µmol/g, P < 0.05] and production [(13.94 ± 3.63) nmol/(g·min) vs. (19.64 ± 3.48) nmol/(g·min), P < 0.05] of H(2)S in lung tissue compared with those without receiving HDX treatment. As for the expression of CSE in small pulmonary arteries (SPAs), compared with control group, the expression of CSE in intima [(0.31 ± 0.02) vs. (0.36 ± 0.01), P < 0.01] and media [(0.27 ± 0.01) vs. (0.30 ± 0.01), P < 0.01] in rats of hypoxic group was decreased significantly. While compared with hypoxic group, the expression of CSE in intima [(0.35 ± 0.02) vs. (0.31 ± 0.02), P < 0.01] in SPAs of hypoxic + SO(2) group was increased significantly. With HDX treatment, the expression of CSE in intima [(0.26 ± 0.01) vs. (0.31 ± 0.02), P < 0.01] in SPAs of hypoxic group was lower than that without HDX treatment. As for the expression of MPST in SPAs, compared with hypoxic group, the expression of MPST in media [(0.32 ± 0.02) vs. (0.29 ± 0.01), P < 0.01] in SPAs of hypoxic + SO(2) group was increased significantly.
SO(2) might upregulate H(2)S/CSE and H(2)S/MPST pathways in pulmonary arteries of hypoxic rats.
探讨二氧化硫（SO₂）对低氧性肺动脉高压发病机制中硫化氢（H₂S）/胱硫醚-γ-裂解酶（CSE）和H₂S/巯基丙酮酸硫转移酶（MPST）途径的影响。
将32只雄性Wistar大鼠随机分为四组：对照组（n = 8）、低氧组（n = 8）、低氧+SO₂组（n = 8）和低氧+羟肟酸（HDX）组（n = 8）。实验21天后，分别测定每只大鼠肺组织中H₂S的浓度和生成量。采用免疫组织化学方法检测大鼠肺小动脉内膜和中膜中CSE和MPST的蛋白表达。
与对照组相比，低氧组大鼠的平均肺动脉压（mPAP）显著升高[（33.38±6.32）mmHg对（16.74±3.81）mmHg，P < 0.01]。与低氧组相比，低氧+SO₂组大鼠的mPAP显著降低[（29.65±2.53）mmHg对（33.38±6.32）mmHg，P < 0.01]。然而，与低氧组相比，低氧+HDX组大鼠的mPAP显著升高[（39.44±6.26）mmHg对（33.38±6.32）mmHg，P < 0.01]。与对照组相比，低氧组大鼠肺组织中H₂S的浓度[（2.02±0.43）μmol/g对（3.11±0.42）μmol/g，P < 0.01]和生成量[（19.64±3.48）nmol/（g·min）对（28.20±5.95）nmol/（g·min），P < 0.05]均显著降低。给予SO₂处理后，与未接受SO₂处理的低氧大鼠相比，低氧大鼠肺组织中H₂S的浓度[（2.73±0.20）μmol/g对（2.02±0.43）μmol/g，P < 0.01]和生成量[（26.24±1.92）nmol/（g·min）对（19.64±3.48）nmol/（g·min），P < 0.01]均升高。给予HDX处理后，与未接受HDX处理的低氧大鼠相比，低氧大鼠肺组织中H₂S的浓度[（1.64±0.23）μmol/g对（2.02±0.43）μmol/g，P < 0.05]和生成量[（13.94±3.63）nmol/（g·min）对（19.64±3.48）nmol/（g·min），P < 0.05]均显著降低。至于肺小动脉（SPAs）中CSE的表达，与对照组相比，低氧组大鼠内膜[（0.31±0.02）对（0.36±0.01），P < 0.01]和中膜[（0.27±0.01）对（0.30±0.01），P < 0.01]中CSE的表达均显著降低。与低氧组相比，低氧+SO₂组SPAs内膜中CSE的表达显著升高[（0.35±0.02）对（0.31±0.02），P < 0.01]。给予HDX处理后，低氧组SPAs内膜中CSE的表达[（0.26±0.01）对（0.31±0.02），P < 0.01]低于未接受HDX处理的低氧组。至于SPAs中MPST的表达，与低氧组相比，低氧+SO₂组SPAs中膜中MPST的表达显著升高[（0.32±0.02）对（0.29±0.01），P < 0.01]。
SO₂可能上调低氧大鼠肺动脉中H₂S/CSE和H₂S/MPST途径。
