罗格列酮对野百合碱诱导肺动脉高压大鼠肺血管病变的影响  

Protective effects of rosiglitazone intervention on monocrotaline.induced pulmonary arterial hypertension in rats and related inflammatory mechanisms

作　　者：王晓芳[1] 陆慰萱[2] 郭军[3] 李国[4] 张运剑[1] 

机构地区：[1]北京积水潭医院呼吸内科,北京100035 [2]中国医学科学院北京协和医学院北京协和医院呼吸科 [3]解放军总医院南楼呼吸科 [4]青岛大学医学院附属医院呼吸科

出　　处：《中华医学杂志》2012年第30期2144-2147,共4页National Medical Journal of China

摘　　要：目的探讨罗格列酮早期干预对野百合碱诱导动脉型肺动脉高压大鼠肺血管病变的作用及机制。方法32只SD大鼠随机分为对照组、模型组及罗格列酮高、低剂量干预组，每组8只。对照组大鼠皮下注射生理盐水后常规饲养，模型组及罗格列酮高、低剂量干预组大鼠皮下注射野百合碱60mg／kg，注射当13起分别以生理盐水（1．5ml／d）、罗格列酮（5mg／kg及2．5mg／kg）每日1次灌胃。21d后测定各组大鼠肺动脉平均压（mPAP），取肺组织观察肺小动脉周围炎症评分，测定肺小动脉管壁中膜厚度占管壁外径百分比（WT％），酶联免疫吸附（ELISA）法测定肺组织匀浆白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）和单核细胞趋化蛋白1（MCP-1）水平。结果罗格列酮高、低剂量干预组mPAP[（27±4）、（28±4）mmHg（1mmHg=0．133kPa）]和WT％（13．1％±3．9％、16．7％±1．7％）较模型组[（37±5）mmHg和45．5％±5．5％]明显低（P〈0．01），但仍高于对照组[（17±3）mm Hg和8．9％±2．3％]（p〈0．05和P〈0．01）；罗格列酮高、低剂量干预组肺小动脉周围炎症评分、肺组织匀浆IL-6、TNF-α及MCP-1水平均明显低于模型组（均P〈0．01）；罗格列酮高剂量干预组各项指标较低剂量干预组有降低趋势（P〉0．05）。结论罗格列酮早期应用可延缓野百合碱诱导的大鼠动脉型肺动脉高压形成及肺血管重构，该作用可能与其抗炎作用有关，其对肺血管的保护作用与剂量有关。Objective To investigate the protective effects of rosiglitazone intervention onmonocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） in rats and the possible mechanisms. Methods Thirty-two Sprague-Dawley rats were randomly divided into 4 groups： control group with a subcutaneous injection of normal saline. PAH group, high-dose and low-dose rosiglitazone intervention groups all with a subcutaneous injection of MCT and then gastric infusion of normal saline （ 1.5 ml/d） , rosiglitazone （5, 2. 5 mg·kg^-1 · d^-1）. At Day 21, the mean pulmonary arterial pressure （mPAP） was detected by right heart catheter. Then rats were sacrificed and their lungs extracted. Perivaseular inflammation was scored with the subjective scale of 0 to 4. The tunica media thickness percentage of small pulmonary arteries （ WT% ） of rats was calculated. Interleukin 6 （ IL-6）, tumor necrosis factor alpha （ TNF- α） and monocyte chemotactic protein 1 （MCP-1） of lung tissue were detected by enzyme-linked immunosorbent assay （ELISA）. Results Compared with the PAH group （ （ 37 ± 5 ） mm Hg （ 1 mm Hg = 0.133 kPa）,45.5%±5.5%）, the mPAP and WT% of the high-dose （（27±4） mm Hg, 13.1% ±3.9%） and low-dose （（28 ± 4） mm Hg, 16. 7% ±1.7%） rosiglitazone intervention group were significantly lower （P 〈 0.01 ）, but were still higher than those of the control group （（ 17 ±3 ） mm Hg, 8.9% ±2. 3 % ） （ P 〈 0. 05 or P 〈 0. 01 ）. The perivaseular inflammation score and levels of IL-6, TNF-α, MCP-1 of high-dose and low-dose rosiglitazone intervention groups were significantly lower than those of thePAH group （P 〈 0. 01 ）. Compared with the low-dose rosiglitazone intervention group, all the above indices of the high-dose rosiglitazone intervention group appeared much lower （P 〉 0. 05 ）. Conclusion The protective effects of rosiglitazone against MCT-induced PH are correlated with drug dose and may be due to the inhibition of inflammation.

关 键 词：高血压 肺性 野百合碱 大鼠 罗格列酮 

分 类 号：R965[医药卫生—药理学]