NVP-BEZ235抑制低氧诱导的大鼠肺部炎症反应  

NVP-BEZ235 inhibited hypoxia induced lung inflammation of rats

作　　者：柴晓宇[1] 易亮[1] 许慧莹[1] 刘钟桧 刘新民[1] CHAI Xiao-yu YI Liang XU Hui-ying LIU Zhong-hui LIU Xin-min(Geriatrics of Peking University First Hospital, BEIJING 100034, China)

机构地区：[1]北京大学第一医院老年科,北京100034

出　　处：《中国新药与临床杂志》2017年第1期30-34,共5页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的评价PI3K/mTOR双重抑制剂NVP-BEZ235对低氧诱导的大鼠肺部炎症及血清炎性因子的作用。方法将18只SD雄性大鼠随机分为对照组、低氧组和NVP-BEZ235干预组(均n=6),低氧组和干预组置于低压低氧(0.5大气压、吸入氧浓度约10%)环境饲养,干预组于实验第1日起给予NVPBEZ235(35 mg·kg^(-1))隔日灌胃给药,对照组匹配常氧饲养,21 d后全部动物以5%戊巴比妥钠麻醉后取材。肺组织固定后石蜡包埋并行HE染色及Masson染色并进行病理评分;ELISA方法检测各组大鼠血清中白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α、转化生长因子(TGF)-β水平。结果低氧组大鼠肺泡炎症评分及肺纤维化评分显著高于对照组(P<0.01),NVP-BEZ235干预组炎症评分及肺纤维化评分显著低于低氧组(P<0.01)。低氧组大鼠血清IL-1β、TNF-α、TGF-β较对照组显著升高(P<0.01),干预组IL-1β、TNF-α较低氧组降低(P<0.01),而TGF-β水平增高(P<0.05)。结论 NVP-BEZ235可以抑制低氧诱导的肺动脉高压大鼠的肺部炎症及纤维化水平,抑制血清IL-1β和TNF-α水平升高,提高血清TGF-β的表达水平。AIM To evaluate the effects of PI3K/rnTOR dual inhibitor NVP-BEZ235 on hypoxia induced lung inflammation and inflammatory eytokines of rats. METHODS Eighteen male SD rats were randomly assigned into control group, hypoxia group and NVP-BEZ235 intervene group （n = 6 in each group）. Rats in the hypoxia group and the intervene group were raised in hypobaric hypoxia environment （0.5 ATM with inhaled oxygen concentration of about 10%）. The intervention group was given NVP-BEZ235 （35 mg·kg^-1, po） every two days from day one to the end. The control group was raised with normal oxygen. All rats were sacrificed with 5% pentobarbital sodium after 21 days. Then the lung tissues were fixed, paraffin embedded in parallel for further HE staining and Masson staining and pathological score. ELISA method was performed to detect the serum levels of interleukin- 1β （IL- 1β）, tumor necrosis factor-α （TGF-β） of rats. RESULTS Compared with the control group, （TNF-α） and transforming growth factor beta the alveolar inflammation score and pulmonary fibrosis score in the hypoxia group were increased （P 〈 0.01）, those in the NVP-BEZ235 intervene group were lower than the hypoxia group （P 〈 0.01 ）. The serum levels of IL- 1β, TNF-α and TGF-β were significantly higher in the hypoxia group than in the control group, while the IL-1β and TNF-α in the intervene group were lower and the TGF-β was higher than those in the hypoxia group （P 〈 0.01 or P 〈 0.05）. CONCLUSION NVP-BEZ235 could inhibit the pulmonary inflammation and fibrosis in hypoxia induced rats, it could inhibit the increase of IL-1β and TNF-α levels in serum, and promote the level of TGF-β.

关 键 词：NVP-BEZ235 炎症 肺动脉 低氧 转化生长因子Β 

分 类 号：R543.2[医药卫生—心血管疾病]