二氧化硫对低氧性肺动脉高压大鼠肺动脉结构的影响

目的 探讨二氧化硫(sulfur dioxide,SO2)对于低氧性肺动脉高压大鼠肺动脉结构的影响.方法 将大鼠分为3组:对照组(n=8)、低氧组(n=8)和低氧+SO2组(n=10,给予Na2SO3/NaHSO3).对低氧组和低氧+SO2组大鼠进行低氧处理21 d.同时对照组置于常氧环境.检测各组大鼠肺动脉平均压.并通过光镜检测肌型小动脉相对中膜厚度(RMT),应用透射电镜观察各组大鼠肺小动脉超微结构的变化,检测血浆SO2含量.结果 低氧组大鼠肺动脉平均压(5.12±0.51)kPa]较对照组(2 25±0.50)Ida]高(t=5.091,P＜0.01),低氧组肺动脉RMT测定值(9.66±1.27)较对照组(6.83±1.57)高(t=3.392,P＜0.01),超微结构观察显示低氧组大鼠肺小动脉内皮细胞体积增大变性,内弹力层疏松厚薄不均.平滑肌细胞体积增大,细胞器丰富,细胞间见胶原原纤维增多,同时低氧组血浆SO2含量(27.01±4.17)tunol/L]较对照组(33.36±5.62)μmol/L]低(t=3.767,P＜0.05);低氧+SO2组大鼠的肺动脉平均压(3.94±0.33)kPa]较低氧组(5.12 ±0.51)kPa]低(t=2.712,P＜0.01),低氧+SO2组RMT测定值(6.97±1.83)较低氧组(9.66±1.27)低(t=3.009,P＜0.01),超微结构观察显示给予SO2干预后上述改变较低氧组明显改善,同时血浆SO2含量(29.89±4.52)μml/L]较低氧组(27.01±4.17)μmol/L]高(t=1.263,P＞0.05).结论 SO2对低氧性肺动脉高压大鼠肺小动脉结构具有重要的调节作用.

Effect of sulfur dioxide on pulmonary vascular structure of hypoxic pulmonary hypertensive rats

Objective Hypoxic pulmonary hypertension is an important pathophysiologic process of various cardlovaacular diseases.Sulfur dioxide(SO2)was considered as a kind of toxic gas previously,but recent studies suggested that SO2 could act as a key bioactive molecule in the pathogenesis of cardiovascular diseases.Therefore.this study wag designed to examine the effect of sulfur dioxide on pulmonary vascular structure of hypoxic pulmonary hypertensive rats treated with SO2 donor substances.Methods The rats were randomly divided into 3 groups:control group(n=8),hypoxic group(n=8)and hypoxie+SO2 group(n=10,treated with SO2 donor Na2SO3/NaHSO3).The rats of hypoxic group and hypoxic+ SO2 group were under a hypoxic condition for 21 days.while the rats of control group were exposed to loom air.The mean pulmonary artery pressure was tested by means of right cardiac catheterization and the content of SO2 in plasma was investigated by high performance liquid chromatography(HPLC).The change in relative medial thickness(RMT)of pulmonary arteries was examined under optical microscope.The ulIra-structural changes were observed under a transmission electron microscope.The data weTe analyzed through one-way analysis of variance(pzvow)by SPSS 13.0 software.Results Compared with control group(2.25±0.50)kPa],the mean pulmonary artery pressure of hypoxic group(5.12±0.51)kPa]raised significantly(t=5.091,P＜0.01)and RMT of hypoxic group(9.66±1.27)compared with control group(6.83±1.57)significantly raised(t=3.392,P＜0.01).Ultrastrucmral observation showed the proliferation and degeneration of endothelial cells in snlall pulmonary arteries in tats with pulmonary hypertension.The internal elastic lamina was irregular. The proliferation of medial smooth muscle cells of arteries was shown at the level of respiratory brenchioles. The collagens also increased. Meanwhile,compared with control group (33. 36±5.62)μmol/L],the content of SO2 in plasma of hypoxic group (27.01±4. 17) μmol/L]declined (t =2.067,P ＜0.05). Whereas compared with that of hypoxic group(5. 12±0. 51)kPa] ,the mean pulmonary artery pressure of hypoxic + SO2 group ( 3.94±0. 33 ) kPa] declined ( t = 2. 712,P ＜0. 01 ) and RMT of hypoxic + SO2 group (6. 97 ± 1.83 ) decreased compared with hypoxic group (9. 66 ±1.27) (t =3.009,P＜0.01). Compared with those of hypoxic group,the pulmonary artery ultrastructural changes in hypoxic group ameliorated obviously after using exogenous sulfur dioxide donor. The endothelial cells became flat and the smooth muscle cells of arteries slightly enlarged and arranged regularly. At the same time,compared with hypoxic group (27.01±4. 17)μmoL/L],the content of SO2 in plasma of liypoxic + SO2 group ( 29. 89±4. 52 ) μmol/L ] raised ( t = 1. 263,P ＞ 0. 05 ). Conclusion Sulfur dioxide plays an important role in the regulation of small pulmonary artery structural changes in hypoxic pulmonary hypertensive rats. The hypoxic pulmonary hypertensive damages can be ameliorated significantly after using exogenous SO2 donor.