罗格列酮通过激活PPARγ改善肺动脉高压大鼠肺血管病变的研究  

Rosiglitazone attenuates monocrotaline-induced pulmonary arterial hypertension in a rat model through activated PPARγ

作　　者：李赫[1,4] 孙德飞 张国斌 卢巍 王东亮 徐婷婷 赵洪文[4] 

机构地区：[1]沈阳军区第202医院呼吸科,110001 [2]沈阳军区第202医院病理科,110001 [3]沈阳军区第202医院药理基地,110001 [4]中国医科大学附属第一医院呼吸病研究所,沈阳110001

出　　处：《国际呼吸杂志》2014年第17期1311-1315,共5页International Journal of Respiration

基　　金：辽宁省医学高峰建设工程重点科研项目（200922）

摘　　要：目的探讨过氧化物酶体增殖物激活受体γ（PPARγ）及其配体对野百合碱诱导的肺动脉高压大鼠肺血管病变的作用及机制。方法将40只SD大鼠随机分为4组：正常对照组、罗格列酮对照组、野百合碱组和罗格列酮干预组。野百合碱组和罗格列酮干预组给予野百合碱60mg／kg皮下注射；2个对照组给予等体积生理盐水皮下注射。罗格列酮对照组和罗格列酮干预组自注射生理盐水或野百合碱后，给予罗格列酮生理盐水混悬液（4．0mg·kg^-·d^-1）灌胃，正常对照组和野百合碱组每日给予等体积生理盐水灌胃，共4周。以右心导管测定右室收缩压（RVSP）和肺动脉平均压（mPAP），计算右心肥厚指数（RVHI）作为评价右心室肥厚的指标；ELISA法测定血浆N0和内皮素-1（ET-1）水平；采用HE及Elastin Van Gieson染色法观察各级肺动脉的病理改变，测定并计算中膜厚度百分比（WT％）评价血管重塑程度；免疫组织化学法观察PPARγ的表达情况。结果罗格列酮干预组mPAP（28．2±5．3）mmHg、RVHI（0．35±0．05）和WTO（27．7±7．2）％较野百合碱组明显改善，但仍高于正常对照组。与野百合碱组比较，罗格列酮干预组可升高血浆NO水平（t=2．363，P〈0．05）、降低ET-1水平（t=3．522，P〈0．01），并抑制肺小血管壁的增厚（t=5．192，P〈0．01）。结论罗格列酮可通过激活PPARγ改善野百合碱诱导的肺动脉高压大鼠肺血管重塑，并延缓肺动脉高压的进展。Objective To investigate the protective effects of peroxisome proliferator-activated receptor gamma （PPART） and its agonist on monocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） in rats and the possible molecular mechanisms： Methods Forty Sprague-Dawley （SD） rats were randomly divided into a control group, a rosiglitazone control group,a monocrotaline group and a rosiglitazone intervention group. The rat models of pulmonary hypertension were replicated by subcutaneous injection of monocrotaline （60 mg/kg） by one time in： the monocrotaline group and the rosiglitazone intervention group, the other groups were treated with subcutaneous injectidn of saline. And then rosiglitazone （4.0 mg/kg） was administered by gastric tube in the rosiglitazone control group and rosiglitazone intervention group once daily, at the same time, the control group and monocrotaline group were only administered saline by gastric tube. After 4 weeks, the right ver/tricular systolic pressure （RVSP） and mean pulmonary aterial pressure （mPAP） were detected by right heart catheter. Right ventricular hypertrophy index （RVHI） was calculated for the assessment of right ven tricular hypertrophy. The blood was took from the abdominal aorta for detection of NO and ET-1 levels by ELISA and then the lung tissue sections were stained with HE and elastin-van Gieson for histopathological examination and the calculation of tunica media thickness percentage （WT%）. Expressions of PPAR7 were detected by immunohistochemistry. Results Compared with the monocrotaline group, the mPAP, RVHI and WT% of rats in rosiglitazone treatment group [-（28.2 ± 5.3） mmHg, （0.35 ± 0.05） and （27.7±7.2） % decreased significantly, but still higher than those of the control group. Rosiglitazone intervention also decreased the plasma ET-1 level （ t =3. 522, P 〈0. 01） and increased the NO level in PAH rats （ t =2. 363, P 〈0.05） ,and reversed the hypertrophy of pulmonary artery wall （ t =5. 192, P�

关 键 词：肺动脉高压 罗格列酮 野百合碱 过氧化物酶体增殖物激活受体Γ 

分 类 号：R544.1[医药卫生—心血管疾病]