本文選題：NVP-BEZ + 炎癥��； 參考：《中國新藥與臨床雜志》2017年01期

【摘要】：目的評價(jià)PI3K/mTOR雙重抑制劑NVP-BEZ235對低氧誘導(dǎo)的大鼠肺部炎癥及血清炎性因子的作用。方法將18只SD雄性大鼠隨機(jī)分為對照組、低氧組和NVP-BEZ235干預(yù)組(均n=6),低氧組和干預(yù)組置于低壓低氧(0.5大氣壓、吸入氧濃度約10%)環(huán)境飼養(yǎng),干預(yù)組于實(shí)驗(yàn)第1日起給予NVPBEZ235(35 mg·kg~(-1))隔日灌胃給藥,對照組匹配常氧飼養(yǎng),21 d后全部動物以5%戊巴比妥鈉麻醉后取材。肺組織固定后石蠟包埋并行HE染色及Masson染色并進(jìn)行病理評分;ELISA方法檢測各組大鼠血清中白細(xì)胞介素(IL)-1β、腫瘤壞死因子(TNF)-α、轉(zhuǎn)化生長因子(TGF)-β水平。結(jié)果低氧組大鼠肺泡炎癥評分及肺纖維化評分顯著高于對照組(P0.01),NVP-BEZ235干預(yù)組炎癥評分及肺纖維化評分顯著低于低氧組(P0.01)。低氧組大鼠血清IL-1β、TNF-α、TGF-β較對照組顯著升高(P0.01),干預(yù)組IL-1β、TNF-α較低氧組降低(P0.01),而TGF-β水平增高(P0.05)。結(jié)論 NVP-BEZ235可以抑制低氧誘導(dǎo)的肺動脈高壓大鼠的肺部炎癥及纖維化水平,抑制血清IL-1β和TNF-α水平升高,提高血清TGF-β的表達(dá)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- 偽, 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- 偽 and TGF- 尾 in hypoxic group were significantly higher than those in control group (P 0.01). The levels of IL-1 尾 -TNF- 偽 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- 偽, and increase the level of serum TGF- 尾 in hypoxic-induced pulmonary hypertension rats.
【作者單位】： 北京大學(xué)第一醫(yī)院老年科;
【分類號】：R56

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