摘要
目的采用皮下微量注射泵持续注射腺苷14d,观察腺苷对低氧所致肺动脉高压的影响及作用机制。方法将SD大鼠分成常氧组、低氧组和腺苷处理组,于低氧[氧浓度(10.0±0.5)%]第7天皮下植入胶囊渗透压泵,腺苷组在低氧处理同时注射腺苷(100μg·kg-·1min-1);另两组泵内含等量生理盐水,持续14d。测尾动脉压力和肺动脉压力,取血浆检测肾素活性(RA)、血管紧张素II(AngII)、内皮素-1(ET-1)、NO水平,取肺动脉作免疫组化检测iNOS蛋白表达。结果(1)低氧致肺动脉压力高于常氧组(P<0.01),而腺苷处理后肺动脉压力低于低氧组(P<0.01);(2)低氧组血浆ET-1水平明显高于常氧组(P<0.01),腺苷治疗组低于低氧组(P<0.01);低氧组血浆NO水平明显低于常氧组(P<0.01),腺苷治疗组高于低氧组(P<0.01);低氧组肺动脉血管iNOS蛋白表达高于常氧组,腺苷处理组肺动脉血管iNOS蛋白表达明显高于低氧组和常氧组(P<0.01);(3)低氧组血浆RA和AngⅡ水平明显高于常氧组(P<0.01),腺苷治疗组则明显低于低氧组(P<0.01)。结论外周持续腺苷给药可降低慢性低氧所致肺动脉高压,其机制与抑制体内肾素血管紧张素系统、内皮素水平,促进肺动脉iNOS表达和增高血浆NO水平有关。
Objective To observe the effects of continuous subcutaneous adenosine infusion on pulmonary hypertension in chronically hypoxic rats. Methods Twenty-four SD rats were randomized into normoxic group, hypoxic＇group and adenosine-treated h.ypoxic group. Hypoxic environment was simulated in a chamber filled with 10% oxygen and 90% nitrogen. After 7 days of hypoxia, adenosine were administered subcutaneously in the rats in adenosine-treated group at the rate of 100 μg·kg^-1 ·min^-1 via an Alzet micro-osmotic pump for 14 days, while the pumps in the other two groups contained normal saline. After 21 days ofhypoxia, pulmonary artery pressure and tail-cuffblood pressure were measured, with the plasma rennin activity （RA）, angiotensin Ⅱ （AngⅡ）, endothelin （ET）-l, and nitric oxide （NO） determined. Inducible nitric oxide synthase （iNOS） expression in the pulmonary artery of the rats was detected using immunohistochemical method. Results The mean pulmonary artery pressure （mPAP） was significantly higher in the hypoxic group than that in the normoxic group （P〈0.01） and in the adenosine-treated group （P〈0.01）. Plasma ET-1 was significantly higher but plasma NO significantly lower in the hypoxic group than in the normoxic group （P〈0.01） and the adenosine-treated group （P〈0.01）. iNOS expression in the pulmonary artery was higher in the hypoxic group than in normoxic group （P〈0.01）, and adenosine significantly increased iNOS expression in comparison with the normoxic and hypoxic groups （P〈0.01）. Plasma RA and AngⅡ in the hypoxic group were significantly higher than those in the normoxic group （P〈0.01） and the adenosine-treated （P〈0.01）. Conclusion Adenosine administered by continuous subcutaneous infusion alleviates chronically hypoxia-induced pulmonary hypertension in rats, in which rennin angiotensin system, ET-1, and iNOS/NO play a role.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2008年第6期1052-1055,共4页
Journal of Southern Medical University
