慢性低O_2高CO_2时NO-sGC-cGMP细胞信号转导通路变化及与肺动脉高压的关系  

Ralationship between the changes of cellular signal transduction of NO-sGC-c GMP and pulmonary hypertension induced by chronic hypoxic hypercapnia

作　　者：徐正祄[1] 夏晓东[1] 管瑜[2] 

机构地区：[1]温州医学院病理生理教研室,浙江温州325027 [2]温州医学院放免室,浙江温州325027

出　　处：《温州医学院学报》2003年第6期361-363,共3页Journal of Wenzhou Medical College

基　　金：浙江省自然科学基金资助项目 ( 396 479)

摘　　要：目的 :探讨慢性低O2 高CO2 性肺动脉高压发生与发展中NO sGC cGMP细胞信号转导通路的变化和作用。方法 :雄性Sprague Dawley大鼠随机分为对照组与低O2 高CO2 肺动脉高压 1w、2w及 4w组。用比色法测定血浆NO含量 ,酶动力学法测定肺组织sGC活性 ,12 5 I 放射免疫法检测肺组织cGMP含量。结果 :低O2 高CO2 1w、2w、4w组mPAP较对照组均明显升高 (P均 <0 .0 1)。而血浆NO含量、肺组织sGC活性和肺组织cGMP含量均显著降低 (分别P <0 .0 5,P <0 .0 1或P <0 .0 0 1)。mPAP与血浆NO含量 (r =-0 .80 7,P <0 .0 1)、与肺组织sGC活性 (r=-0 .754,P <0 .0 1)、与肺组织cGMP含量 (r=-0 .62 1,P <0 .0 1)之间均存在显著负相关。结论 :低O2 高CO2 引起的NO sGCObjective: To clarify changes and effects of cellular signal transduction of NO-sGC-cGM P in the occurrence and development of chronic hypoxic hypercapnic pulmonary hyp ertension. Methods:Male Sprague￣Dawley rats were randomly divided into co ntrol group and hypoxic hypercapnic pulmonary hypertension group,which include H H1w,HH2w and HH4w group. NO content in plasma was determined by spectrophotom etry. sGC activity in lung tissue was detected by enzyme kinetic analysis. cGMP content in lung tissue was examined with ~ 125 I-radioimmunoassay. Results:The mean pulmoanry atery pressure(mPAP)were significant ly higher in HH1w,HH2w and HH4w group compared with control group(all of P<0.01). But plasma NO concentration,lung homogenates sGC activity and cGMP concentration were significantly lower(P<0.05, P<0.01,P<0.001,respectively)in HH1w, HH2w and HH4w group compared with control group. There were negative correlation among plasm a NO concentration(r=-0.807,P<0.01),lung tissue sGC activity(r= -0.754,P<0.01),cGMP cencentration(r=-0.621,P<0.01)and mPAP.Conclusion:These findings suggest that the inhibition of NO- sG C-cGMP cellular signal transduction pathway by hypoxia and hypercapnia plays an important role in the mechanism of the decreased relaxation of pulmonary artery and the development of pulmonary hypertension.

关 键 词：低氧 高碳酸血 肺动脉高压 一氧化氮 可溶性鸟苷酸环化酶 环磷酸鸟苷 信号转导 

分 类 号：R363.2[医药卫生—病理学] Q753[医药卫生—基础医学]