NVP-BEZ235抑制低氧诱导的大鼠肺部炎症反应
发布时间:2018-04-16 12:28
本文选题:NVP-BEZ + 炎症 ; 参考:《中国新药与临床杂志》2017年01期
【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(P0.01),NVP-BEZ235干预组炎症评分及肺纤维化评分显著低于低氧组(P0.01)。低氧组大鼠血清IL-1β、TNF-α、TGF-β较对照组显著升高(P0.01),干预组IL-1β、TNF-α较低氧组降低(P0.01),而TGF-β水平增高(P0.05)。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。
[Abstract]:Objective to evaluate the effects of PI3K/mTOR dual inhibitor NVP-BEZ235 on hypoxic induced pulmonary inflammation and serum inflammatory factors in rats.Methods Eighteen SD male rats were randomly divided into control group, hypoxic group and NVP-BEZ235 intervention group (all of them were treated with hypoxia, hypoxia group and intervention group were exposed to low pressure hypoxia of 0.5 atmospheres and inhaled oxygen concentration of about 10 parts).The intervention group was given NVPBEZ235(35 (mg 路kg ~ (-1)) by gavage every other day from the first day of the experiment, while the control group was fed with 5% pentobarbital sodium for 21 days after anaesthesia with 5% pentobarbital sodium.Lung tissue was fixed with paraffin embedded with HE staining and Masson staining. The serum levels of IL-1- 尾, TNF- 伪, TGF- 尾 and TGF- 尾 in serum of rats in each group were detected by Elisa.Results the alveolar inflammation score and pulmonary fibrosis score in hypoxic group were significantly higher than those in control group (P 0.01) and in NVP-BEZ235 intervention group (P 0.01).The serum levels of IL-1 尾 -TNF- 伪 and TGF- 尾 in hypoxic group were significantly higher than those in control group (P 0.01). The levels of IL-1 尾 -TNF- 伪 in intervention group were lower than those in hypoxia group, while the level of TGF- 尾 was higher than that in hypoxia group (P 0.05).Conclusion NVP-BEZ235 can inhibit pulmonary inflammation and fibrosis, increase the levels of serum IL-1 尾 and TNF- 伪, and increase the level of serum TGF- 尾 in hypoxic-induced pulmonary hypertension rats.
【作者单位】: 北京大学第一医院老年科;
【分类号】:R56
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