一氧化氮对慢性缺氧高二氧化碳大鼠肺血管尾加压素Ⅱ的影响  

Effect of nitric oxide on urotensin-Ⅱ expression in pulmonary arterioles of rats chronically exposed to hypoxia-hypercapnia

作　　者：吴小脉[1] 范小芳[1] 黄虹[1] 骆健峰[1] 毛孙忠[1] 胡良冈[1] 龚永生[1] 

机构地区：[1]温州医学院肺心病研究室病理生理学教研室,浙江温州325027

出　　处：《中国病理生理杂志》2006年第10期1905-1908,共4页Chinese Journal of Pathophysiology

基　　金：浙江省教育厅科研基金资助项目(No.20020468);温州市科委资助项目(No.Y2003A037)

摘　　要：目的:探讨一氧化氮/L-精氨酸(NO/L-Arg)系统和尾加压素Ⅱ(UⅡ)在大鼠慢性缺氧(O2)高二氧化碳(CO2)肺动脉高压病理过程的作用及关系。方法:40只大鼠随机分成4组(每组各10只):正常对照组(A组)、慢性缺O2高CO2加生理盐水4周组(B组)、慢性缺O2高CO2加L-Arg脂质体4周组(C组)、慢性缺O2高CO2加N-硝基-L-精氨酸甲酯(L-NAME)4周组(D组)。免疫组化法和组织原位杂交法检测肺小动脉UⅡ和UⅡmRNA、UⅡ受体(UT)mRNA的表达,并观察肺小动脉显微结构的变化。结果:(1)肺动脉平均压(mPAP)、右心室(RV)和左心室+室间隔(LV+S)重量比值[RV/(LV+S)]:B组高于A组(均P<0.05);C组低于B组(均P<0.01);D组两指标不仅高于A组(P<0.01和<0.05),且mPAP也高于B组(P<0.01)。(2)肺小动脉管壁面积/管总面积(WA/TA)和中膜厚度(PAMT):B组显著大于A组(P<0.05);C组与B组的差异也有显著性(P<0.01);而D组WA/TA也显著高于A组。(3)肺小动脉UⅡ、UⅡmRNA、UT mRNA表达:同A组比较,B组、D组各指标都显著增高(均P<0.01);C组UⅡ、UⅡmRNA的表达较B组明显下调(P<0.01),同A组比较,其UⅡ表达下调但UTmRNA表达增加(均P<0.01);D组UⅡ表达较B组低,而UT mRNA表达较B组高(均P<0.01)。结论:慢性缺O2高CO2肺动脉高压的发生发展可能与UⅡ的异常表达增加有关,而外源性NO可能有抑制UⅡ的作用。AIM： To investigate the roles of nitric oxide/L - arginine （ NO/L - Arg） pathway and urotensin - Ⅱ （ U Ⅱ ） in the development of pulmonary hypertension induced by chronic hypoxia - hypercapnia in rats. METHODS ： Forty male Sprague - Dawley rats were randomly divided into four groups （ n = 10） ： normal control group （A） , hypoxia - hyper- capnia ＋ saline group （ B）, hypoxia - hypercapnia ＋ L - Arg liposome group （C） and hypoxia - hypercapnia ＋ N - nitro - L - arginine methyl ester （ L - NAME） group （D）. Contents of U Ⅱ , U Ⅱ mRNA and receptor of U Ⅱ （UT） mRNA in pul- monary arterioles were measured with immunohistochemistry analysis and in situ hybridization, respectively. Change of small pulmonary vascular microstructure was also investigated. RESULTS ： （ 1 ） The mean pulmonary artery pressure （mPAP） and the weight ratio of right ventricle to left ventricle plus septum [ RV/（ LV ＋ S）] in B and D groups were all higher than those in A group （ respectively, P 〈 0. 05 ）, with C group significantly lower than those in B group （ respectively, P 〈 0. 01 ）. （2） Light microscopy showed that the ratio of vessel wall area to total area （WA/TA） and the media thickness of pulmonary arterioles （PAMT） in B group were higher than those in A group （P 〈 0. 05 ）, with C group significantly lower than those in B group. （ 3 ） The contents of U Ⅱ , U Ⅱ mRNA and UT mRNA in pulmonary arterioles in B and D groups were all higher than those in A group （respectively, P 〈0.01 ） , while the expression of U Ⅱ and U Ⅱ mRNA in C group were lower than those in B group （P 〈 0. 01 ）. CONCLUSION： The pathological process of pulmonary hypertension induced by chronic hypoxia- hypercapnia might be related to upregulation of U Ⅱ located in pulmonary arterioles, which might be partially inhibited by exogenous NO in rats.

关 键 词：一氧化氮 尾加压素Ⅱ 缺氧 高血压 肺性 

分 类 号：R363[医药卫生—病理学]