慢性低氧对HPH大鼠RAS经典轴和反向调节轴的影响  

Effects of chronic hypoxia on the classical axis and reverse regulated axis of the RAS in HPH rats

作　　者：孙旭阳 杨占婷[3] 南星梅 顾存林[3] 芦殿香[1,3] 李占强[1,3] SUN Xu-yang;YANG Zhan-ting;NAN Xing-mei;GU Cun-lin;LU Dian-xiang;LI Zhan-qiang(Research Center for High altitude Medicine,Key Laboratory of Ministry of Education for High Altitude Medicine,Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province(Qinghai-Utah Joint Research Key Lab for High Altitude Medicine),Qinghai UniversityQinghai,Xining 810001;School of Ecological and Environmental Engineering,Qinghai university,Xining,810016;Medical College of Qinghai University,Qinghai,Xining 810001)

机构地区：[1]青海大学高原医学研究中心,高原医学教育部重点实验室,青海省高原医学应用基础重点实验室(青海-犹他高原医学联合重点实验室),青海西宁810001 [2]青海大学生态环境工程学院,青海西宁810016 [3]青海大学医学部,青海西宁810001

出　　处：《中国高原医学与生物学杂志》2022年第4期240-247,共8页Journal of Chinese High Altitude Medicine & Biology

基　　金：国家自然科学基金项目(81860768,82060786,32060088);青海省科技厅应用基础项目(2020-ZJ-784);中国科学院西部之光项目;青海省“昆仑英才·高端创新创业人才”计划项目。

摘　　要：目的探讨慢性低氧对HPH大鼠RAS经典轴和反向调节轴的影响。方法选取8周龄SD大鼠20只,随机分为对照组与低氧组,对照组大鼠在西宁地区喂养,低氧组在低压氧舱(模拟海拔4500 m)喂养,各组大鼠分别给予充足的食物和活动空间,28 d后采用右心导管术测定平均肺动脉压(mPAP);取腹主动脉血检测血常规;取各组大鼠肺组织用苏木精-伊红(HE)染色,应用图像采集系统及图像分析软件观察并计算肺血管管壁面积占血管总面积的百分比(WA%)、管壁厚度占血管直径的百分比(WT%)以及管腔面积与血管总面积的百分比(LA%);用免疫组化法检测肺动脉内皮标志物CD31抗原的表达;用蛋白免疫印迹法检测ACE、AngⅡ、AT1R、ACE2和Mas蛋白的表达。结果与对照组相比,低氧组大鼠的mPAP显著升高(P<0.05)。血常规结果显示,低氧组大鼠白细胞(WBC)、红细胞(RBC)、血红蛋白(HGB)水平较对照组显著升高;而血小板(PLT)数量较对照组显著降低(P<0.05)。形态学结果显示,低氧组大鼠肺血管管壁厚度显著增加,管腔狭窄,WA%与WT%较对照组显著升高(P<0.05),LA%较对照组显著降低(P<0.05)。免疫组化结果显示,低氧组大鼠肺动脉内皮标志物CD31抗原的表达较对照组显著降低。蛋白免疫印迹结果显示,与对照组相比,ACE、AngⅡ、AT1R蛋白的表达量在低氧刺激下显著升高(P<0.05),而ACE2、Mas蛋白表达量在低氧损伤后明显降低(P<0.05)。结论低氧性肺动脉高压大鼠肺组织中的RAS经典轴ACE/AngⅡ/AT1R上调,反向调节轴ACE2/Ang(1-7)/Mas下调。Objective To investigate the effects of chronic hypoxia on the classical and reverse regulated axes of the RAS in HPH rats.Method 20 healthy SD rats were selected and randomly divided into control and hypoxic groups.The control rats were fed in Xining and the hypoxic rats were fed in a low-pressure oxygen chamber at a simulated altitude of 4500 m.Mean pulmonary artery pressure(mPAP)was measured by right heart catheterization after 28 d;The lung tissues were stained with hematoxylin-eosin(HE),The pulmonary vessel wall area(WA%),vessel wall thickness(WT%),and lumen area(LA%)were analyzed by image software.;Western blotting was used to detect the expression of ACE,AngⅡ,AT1 R,ACE2,and Mas proteins.Result Compared with the control group,the mPAP was significantly higher in the hypoxic group(P<0.05).The results of complete blood count showed that the white blood cell count(WBC),red blood cell count(RBC),hematocrit(HCT)and the level of hemoglobin(HGB)in hypoxia group were significantly higher than those in control.And the morphological results showed that the walls of the pulmonary vessels were significantly thickened and the lumen was narrowed in the hypoxic group.WA%and WT%were significantly higher(P<0.05)and LA%was significantly lower(P<0.05),Immunohistochemical results showed that the expression of CD31 antigen,a marker of pulmonary artery endothelium,was significantly lower in the hypoxic group compared with the control group(P<0.05).compared to the control group.Western blotting showed that the expression of ACE,AngⅡ,and AT1 R proteins were significantly increased under hypoxic stimulation compared to the control group(P<0.05),while the expression of ACE2 and Mas proteins were significantly decreased after hypoxic injury(P<0.05).Conclusion Chronic hypoxia can upregulate the RAS classical axis while downregulate the reverse regulatory axis,ACE/AngⅡ/AT1 R axis was up-regulated while ACE2/Ang(1-7)/Mas axis was down-regulated in lung tissue of HPH rats.

关 键 词：低氧 肾素-血管紧张素系统 低氧性肺动脉高压 

分 类 号：R364.4[医药卫生—病理学]