PPARγ在肺动脉高压大鼠肺血管重建中的作用与NOX-4的关系  

Relationship between effect of PPARγ in pulmonary vascular remodeling and NOX-4 in rats with pulmonary hypertension

作　　者：刘跃丹 张加强 李陈茜 苌恩强 孟凡民 Liu Yuedan;Zhang Jiaqiang;Li Chenxi;Chang Enqiang;Meng Fanmin(Department of Anesthesiology,People's Hospital of Zhengzhou University,Zhengzhou 450003,China)

机构地区：[1]郑州大学人民医院麻醉科,4530003

出　　处：《中华麻醉学杂志》2018年第12期1530-1534,共5页Chinese Journal of Anesthesiology

摘　　要：目的评价过氧化物酶体增殖物激活受体γ(PPARγ)在肺动脉高压大鼠肺血管重建中的作用与NADPH氧化酶4(NOX-4)的关系。方法健康成年雄性SD大鼠32只,2月龄,体重200~250g,采用随机数字表法分为4组(n=8):对照组(C组)、肺动脉高压组(PH组)、PPARγ激动剂罗格列酮处理组(R组)和PPARγ拮抗剂GW9662处理组(G组)。PH组采用颈背部皮下单次注射野百合碱60mg/kg的方法制备肺动脉高压模型。R组和G组在注射野百合碱后,给予罗格列酮生理盐水混悬液5mg·kg^-1·d^-1或GW9662溶液2mg·kg^-1·d^-1灌胃,连续4周。于模型制备后4周开胸测定平均肺动脉压(mPAP),随后处死大鼠,取肺组织标本,光镜下观察病理学变化,计算肺小动脉中膜厚度百分比,采用Westernblot法和RT-PCR定量法检测PPARγ、NOX-4及其mRNA表达水平。结果与C组比较,PH组、R组和G组mPAP及中膜厚度百分比升高,肺组织PPARγ及其mRNA表达下调,NOX-4及其mRNA表达上调(P<0.05);与PH组比较,R组mPAP及中膜厚度百分比降低,肺组织PPARγ及其mRNA表达上调,NOX-4及其mRNA表达下调,G组mPAP及中膜厚度百分比升高,肺组织PPARγ及其mRNA表达下调,NOX-4及其mRNA表达上调(P<0.05)。结论PPARγ在大鼠肺动脉高压发展和肺血管重建中内源性保护作用的机制可能与下调NOX-4表达水平有关。Objective To evaluate the relationship between the effect of peroxisome proliferator-activated receptor-γ(PPARγ) in pulmonary vascular remodeling and NADPH oxidase 4 (NOX-4) in rats with pulmonary hypertension. Methods Thirty-two healthy adult male Sprague-Dawley rats, aged 2 months, weighing 200-250 g, were divided into 4 groups(n=8 each)using a random number table method: control group (group C), pulmonary arterial hypertension group (group PH), PPARγ agonist rosiglitazone treatment group (group R), and PPARγ antagonist GW9662 treatment group (group G). In group PH, monocrotaline 60 mg/kg was injected subcutaneously in the neck and back to induce pulmonary hypertension.The suspension of rosiglitazone and normal saline 5 mg·kg-1·d-1 and GW9662 solution 2 mg·kg-1·d-1 were administered by intragastric gavage after injecting monocrotaline, in group R and group G, respectively, for 4 consecutive weeks.The mean pulmonary arterial pressure (mPAP) was measured at 4 weeks after establishing the model.The animals were then sacrificed, and the lungs were removed for microscopic examination of the pathological changes (with a light microscope) and for determination of the expression of PPARγ and NOX-4 protein and mRNA in lung tissues(by real-time polymerase chain reaction or Western blot). The percentage of media thickness of pulmonary arterioles was calculated. Results Compared with group C, the mPAP and percentage of media thickness of pulmonary arterioles were significantly increased, the expression of PPARγ protein and mRNA was down-regulated, and the expression of NOX-4 protein and mRNA was up-regulated in PH, R and G groups (P<0.05). Compared with group PH, the mPAP and percentage of media thickness of pulmonary arterioles were significantly decreased, the expression of PPARγ protein and mRNA was up-regulated, and the expression of NOX-4 protein and mRNA was down-regulated in group R, and the mPAP and percentage of media thickness of pulmonary arterioles were significantly increased, the expression of PPAR

关 键 词：PPARΓ 高血压 肺性 肺动脉 细胞增殖 NADPH氧化酶 

分 类 号：R544.1[医药卫生—心血管疾病]