腺苷A_(2a)受体在红景天苷调节大鼠低氧性肺动脉高压中的作用  

Effects of A_(2a) adenosine receptor on hypoxic pulmonary hypertension in rats treated with salidroside

作　　者：黄晓颖[1] 樊荣[2] 蔡学定[1] 张协[1] 卢园园[1] 王良兴[1] 

机构地区：[1]温州医学院附属第一医院呼吸内科,浙江温州325003 [2]扬州市江都人民医院呼吸内科,江苏扬州225200

出　　处：《中国病理生理杂志》2012年第12期2135-2140,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81270110);浙江省自然科学基金资助项目(No.Y2101208);温州市科技局项目(No.Y20100190)

摘　　要：目的:探讨腺苷A2a受体(A2aAR)对低氧性肺动脉高压大鼠的保护作用及红景天苷对大鼠低氧性肺动脉高压的调控作用及其机制。方法:将SD大鼠60只随机分为6组:正常组、低氧组、低氧+红景天苷低剂量组、低氧+红景天苷中剂量组、低氧+红景天苷高剂量组、低氧+A2aAR激动剂(CGS-21680)组。测定各组大鼠平均肺动脉压(mPAP)、平均颈动脉压(mCAP)和右心室(RV)/(左心室+室间隔)(LV+S),观察各组肺细小动脉显微结构变化;用免疫组化法和原位杂交法测定肺细小动脉管壁A2aAR含量的变化;用实时荧光定量PCR法和Western blotting法测定肺组织匀浆A2aAR mRNA和蛋白含量的变化。结果:(1)低氧组大鼠mPAP明显高于正常对照组,A2aAR激动剂组和红景天苷高剂量组可以明显降低mPAP,红景天苷中、低剂量组mPAP虽有下降趋势,但差异无统计学意义。(2)低氧组大鼠RV/(LV+S)显著高于正常组,A2aAR激动剂组和红景天苷中、高剂量组RV/(LV+S)显著低于低氧组,红景天苷低剂量组较低氧组有减低趋势,但差异无统计学意义。(3)低氧组大鼠肺细小动脉重构显著,A2aAR激动剂组及红景天苷低、中、高剂量组肺血管重构较低氧组明显减轻。(4)低氧组肺血管和肺组织A2aAR mRNA和蛋白表达均明显高于正常组,A2aAR激动剂组和红景天苷高剂量组肺血管和肺组织A2aARmRNA和蛋白水平均较低氧组进一步升高。结论:A2aAR对低氧性肺动脉高压大鼠具有保护作用;红景天苷能够上调低氧性肺动脉高压大鼠肺血管和肺组织A2aAR的表达,该通路可能是其减轻低氧性肺动脉高压和肺血管重建的重要机制。AIM： To study the protective effect of A2a adenosine receptor （A2aAR） on hypoxic pulmonary hy- pertension in the rats treated with salidroside. METHODS ： Sprague - Dawley rats were randomly divided into 6 groups ： normal control group, hypoxia group, hypoxia ＋ salidroside （ low dose） group, hypoxia ＋ salidroside （ median dose） group, hypoxia ＋ salidroside （ high dose） group, and hypoxia ＋ CGS - 21680 （ a selective agonist of A2a AR） group. Pulmonary hy- pertension in the rats was produced for 4 weeks. Mean pulmonary artery pressure （mPAP）, mean carotid arterial pressure （reCAP） and the weight ratio of right ventricle/（left ventricle ＋ septum） [ RV/（ LV ＋ S） ] were measured. The expression of A2aAR in the pulmonary arterioles was determined by immunohistochemistry and in situ hybridization. The mRNA ex- pression of A2aAR in the lung tissues was detected by real - time RT - PCR. The protein level of A2aAR in the lung tissues was analyzed by Western blotting. RESULTS： The mPAP in hypoxia group was significantly higher than that in normal control group. The mPAP in hypoxia ＋ salidroside （high dose） group and CGS -21680 group was significantly lower than that in hypoxia group. RV/（ LV ＋ S） in hypoxia group were significantly higher than that in normal control group. RV/（ LV ＋ S） in hypoxia ＋ salidroside （median dose） group, hypoxia ＋ salidroside （high dose） group and CGS-21680 group were lower than that in hypoxia group. The ratio of vessel wall area/vessel total area（WA/TA） in hypoxia group was significant- ly higher than that in normal control group. WA/TA in hypoxia ＋ salidroside （ low dose） group, hypoxia ＋ salidroside （ me- dian dose） group, hypoxia ＋ salidroside （high dose） group and CGS21680 group were obviously lower than that in hypoxia group. The expression of A2aAR was significantly higher in hypoxia group than that in normal control group. The expression of A2aAR in hypoxia ＋ salidroside （high do

关 键 词：肺动脉高压 低氧 红景天苷 腺苷A2A受体 

分 类 号：R363[医药卫生—病理学]