一氧化碳体系对慢性肺心病大鼠肺血管结构重建的抑制作用

The inhibition of pulmonary vessel remodeling by carbon monoxide system in rats with chronic pulmonary heart disease

目的 研究内源性一氧化碳体系对慢性肺心病肺血管结构重建的调控作用。方法 将36只SD大鼠随机分为正常对照组 (A组 )、4周低O2 高CO2 组 (B组 ) ,4周低O2 高CO+ 2 血晶素组 (C组 ) ,每组 12只。测定各组大鼠肺动脉平均压 (mPAP)、右心室 / (左心室 +室间隔 )重量比 [RV/ (LV +S) ]、肺细小动脉显微和超微结构、血CO浓度、血清及肺组织匀浆上清液血红素氧合酶 1(HO 1)活性和肺细小动脉HO 1及其基因表达的变化。结果 (1)B组mPAP为 (2 0 1± 0 8)mmHg(1mmHg =0 .133kPa)、RV/ (LV +S)为 (35 5± 1 7) %、与A组 [(15 3± 1 4 )mmHg、(2 6 7± 1 7) % ]及C组[(16 5± 3 7)mmHg、(30 2± 1 6 ) % ]比较差异有显著性 (P均 <0 0 1)。 (2 )B组肺细小动脉血管结构重建的显微形态测定指标与A、C组比较差异也有显著性 (P <0 0 1)。 (3)B组全血CO含量、血清及肺组织匀浆HO 1活性、肺细小动脉HO 1及其mRNA分别为 (2 1± 0 9) %、(73± 18)nmol·L-1·h-1、(175 1± 311)pmol·mg-1·h-1、0 191± 0 0 12和 0 30 1± 0 0 17,与A组 [(0 5± 0 3) %、(2 5± 8)nmol·L-1·h-1、(385± 4 6 )pmol·mg-1·h-1、0 0 5 9± 0 0 0 5、0 131± 0 0 11]和C组 [(4 9± 2 1) %、(132±39)

Objective To study the effect of carbon monoxide on pulmonary vessel remodeling of chronic pulmonary heart disease Methods Thirty six sprague dawley rats were randomly divided into three groups: control group, and hypoxic hypercapnic group,and hypoxic hypercapnia + hemin group Blood CO concentration (COHb%), activity of HO 1 in blood serum and lung homogenate, pulmonary arteriole micromorphometric index, HO 1 and HO 1 mRNA were measured Results (1) mPAP and RV/(LV+S) were (20 1±0 8) mm Hg and (35 5±1 7)% in hypoxic hypercapnic group, they were significantly higher than those of control group′s (15 3±1 4) mm Hg,(26 7±1 7)%, and those of hypoxic hypercapnia + hemin (activator of HO 1) group′s (16 5±3 7) mm Hg,(30 2±1 6)% ( P <0 01) (2) Pulmonary arteriole micromorphometric index in rats of hypoxic hypercapnic group were significantly higher than those of control group and hypoxic hypercapnia + hemin group ( P <0 01) (3) Blood CO concentration, activity of HO 1 in blood serum and lung homogenate, content of HO 1 and HO 1 mRNA in pulmonary arterioles in rats of hypoxic hypercapnic group were (2 1±0 9)%, (73±18) nmol·L -1 ·h -1 , (1 751±311) pmol·mg -1 ·h -1 , 0 191±0 012 and 0 301±0 017, were significantly higher than those of control group: (0 5±0 3)%, (25±8) nmol·L -1 ·h -1 , (385±46) pmol·mg -1 ·h -1 , 0 059±0 005, 0 131±0 011, but were significantly lower than those of hypoxic hypercapnia + hemin group: (4 9±2 1)%, (132±39) nmol·L -1 ·h -1 , (2 849±426) pmol·mg -1 ·h -1 , 0 272±0 013, 0 339±0 020 ( P <0 01) (4) Correlation analysis revealed that the relationship between carbon monoxide system and pulmonary arteriole micromorphometric index was significantly negative ( P <0 01) Conclusion Up regulation of endogenous carbon monoxide system can inhibit pulmonary vessel remodeling in rats with chronic pulmonary heart disease induced by hypoxia and hypercapnia