可替宁介导PI3K-Akt通路调控IL-10对ARDS大鼠肺组织的保护作用研究  

Study on the protective effect of cotinine on the lung tissues of ARDS rats by regulating IL-10 through the PI3K-AKt pathway

作　　者：贾宝辉 李江[2] 黄敏 陶星宇 张洪泉 JIA Bao-hui;LI Jiang;HUANG Min(Zhengzhou Mingzhou Rehabilitation Hospital,Zhengzhou 450000,China)

机构地区：[1]郑州明州康复医院、明州康复医学研究院,450000 [2]郑州铁路职业技术学院/河南省天然药物提取和医疗技术应用工程研究中心,450000 [3]南昌大学第三附属医院,330003

出　　处：《中国实用医药》2025年第4期177-180,共4页China Practical Medicine

基　　金：河南省高等学校重点科研项目(项目编号:24B310012);郑州铁路职业技术学院2023年度重点科研项目(项目编号:2023KY003);郑州铁路职业技术学院2023年度普通科研项目(项目编号:2023KY021)。

摘　　要：目的探讨可替宁对急性呼吸窘迫综合征(ARDS)大鼠肺组织的保护作用及其机制。方法32只雄性普通级SD大鼠经适应性饲养3 d后随机分为四组:对照组、ARDS组、可替宁组和可替宁+LY294002组[磷脂酰肌醇3激酶-蛋白激酶B(PI3K-Akt)信号通路抑制剂],每组8只。除对照组外,其余组尾静脉注射油酸制备ARDS大鼠模型。模型构建后,可替宁组腹腔注射可替宁,可替宁+LY294002组腹腔注射可替宁+LY294002,对照组和ARDS组腹腔注射生理盐水。观察24 h后,检测四组大鼠动脉血氧分压(PaO_(2)),肺组织病理切片,酶联免疫吸附测定法(ELISA)测血浆白细胞介素-10(IL-10)的浓度,免疫蛋白印迹分析(Westernblotting)测定肺组织磷酸化蛋白激酶B(pAkt)的表达水平。结果对照组PaO_(2)为(106.8±6.3)mm Hg(1 mm Hg=0.133 kPa),ARDS组为(81.6±2.3)mm Hg,可替宁组为(106.2±6.2)mm Hg,可替宁+LY294002组为(84.0±1.7)mm Hg。可替宁组高于ARDS组和可替宁+LY294002组,差异有显著性(P<0.05);与对照组相比无统计学意义(P>0.05)。对照组IL-10为(54.80±5.55)pg/ml,ARDS组为(45.82±3.32)pg/ml,可替宁组为(54.23±5.64)pg/ml,可替宁+LY294002组为(44.55±1.46)pg/ml。可替宁组高于ARDS组和可替宁+LY294002组,差异有显著性(P<0.05);与对照组相比无统计学意义(P>0.05)。四组中pAkt灰度值与内参比值的均数:对照组为(0.74±0.05),可替宁组为(0.75±0.05),可替宁+LY294002组为(0.62±0.04),ARDS组为(0.61±0.06)。可替宁组较ARDS组及可替宁+LY294002组灰度值明显增高,差异有显著性(P<0.05);与对照组相比无统计学意义(P>0.05)。结论可替宁对ARDS大鼠肺组织有保护作用,其机制可能与通过PI3K-Akt信号通路有效地增加抗炎因子IL-10的浓度有关。Objective To explore the protective effect of cotinine on the lung tissues of acute respiratory distress syndrome(ARDS)rats and its mechanism.Methods 32 male,conventional SD rats were divided into four groups after adaptive feeding for 3 d:control group,ARDS group,cotinine group and cotinine+LY294002 group[phosphoinositide-3 kinase/protein kinase B signal pathway(PI3K/Akt)pathway inhibitor],each with 8 rats.ARDS rat models were established by intravenous injection of oleic acid in all groups except control group.After model construction,cotinine group was intraperitoneally injected with cotinine,cotinine+LY294002 group was intraperitoneally injected with cotinine+LY294002,control group and ARDS group were intraperitoneally injected with normal saline.After 24 h of observation,the arterial oxygen partial pressure(PaO_(2))and lung histopathological sections of rats in each group were measured.Plasma interleukin-10(IL-10)concentration was measured by enzyme linked immunosorbent assay(ELISA),and the expression level of phosphorylated proteinkinase B(pAkt)in lung tissue was measured by Western-blotting.Results PaO_(2) was(106.8±6.3)mm Hg(1 mm Hg=0.133 kPa)in the control group,(81.6±2.3)mm Hg in ARDS group,(106.2±6.2)mm Hg in cotinine group,and(84.0±1.7)mm Hg in cotinine+LY294002 group;the cotinine group was higher than ARDS group and cotinine+LY294002 group,and the difference was significant(P<0.05);there was no statistical significance compared with the control group(P>0.05).IL-10 was(54.80±5.55)pg/ml in control group,(45.82±3.32)pg/ml in ARDS group,(54.23±5.64)pg/ml in cotinine group,and(44.55±1.46)pg/ml in cotinine+LY294002 group;cotinine group was higher than ARDS group and cotinine+LY294002 group,and the difference was significant(P<0.05);there was no statistical significance compared with the control group(P>0.05).The mean of pAkt gray value to internal reference ratio was(0.74±0.05)in control group,(0.75±0.05)in cotinine group,(0.62±0.04)in Cotinine+LY294002 group,and(0.61±0.06)in ARDS group;the gra

关 键 词：可替宁 急性呼吸窘迫综合征 磷脂酰肌醇3激酶-蛋白激酶B信号通路 白细胞介素-10 

分 类 号：R965[医药卫生—药理学]