磷脂酰肌醇3激酶抑制剂对慢性阻塞性肺疾病大鼠肺功能及支气管平滑肌厚度的影响  

Effect of inhibitors of phosphoinositide 3-kinases on lung function and bronchial smooth muscle thickness in chronic obstructive pulmonary disease rats

作　　者：陈忠仁 欧宗兴[1] 王蕾 沈彬 梁海梅 杨绪莉 黄实仁 CHEN Zhong-ren;OU Zong-xing;WANG Lei;SHEN Bin;LIANG Hai-mei;YANG Xu-li;HUANG Shi-ren(Department of Pulmonary and Critical Medicine,Haikou Hospital Affiliated to Central South University Xiangya School of Medicine y Haikou 570208,Hainan Province,China)

机构地区：[1]中南大学湘雅医学院附属海口医院呼吸与危重症医学科,海南海口57O208

出　　处：《中国临床药理学杂志》2020年第23期3907-3909,3921,共4页The Chinese Journal of Clinical Pharmacology

基　　金：海南省自然科学基金面上基金资助项目(818MS136);海南省自然科学基金资助项目(818MS136)

摘　　要：目的研究磷脂酰肌醇3激酶(PI3K)抑制剂(LY294002)对慢性阻塞性肺疾病(COPD)大鼠的作用机制。方法用随机数字表法将Wistar大鼠平均分为正常组、模型组和实验组,每组12只。大鼠经气管滴入1μg·μL^-1内毒素2000μL、然后将大鼠放入5%香烟烟雾中熏0.5 h·d^-1来制备COPD大鼠模型。实验组在每次烟熏前1 h均予腹腔注射(1.5 mg·kg^-1)LY294002(50μL);模型组和正常组腹腔注射等量的0.9%NaCl。测定3组大鼠的0.3 s用力呼气容积(FEV0.3)与用力肺活量(FVC)、大鼠支气管气道平滑肌的厚度和细胞PI3K基因表达水平(2-ΔΔCt值)。结果正常组、模型组和实验组的FEV0.3分别为(6.13±0.76),(3.51±0.34)和(5.15±0.59)mL;FVC分别为(7.39±0.52),(5.61±0.48)和(6.88±0.50)mL;这3组的气道平滑肌厚度分别为(10.31±0.61),(19.80±1.53)和(14.40±0.64)μm2·μm^-1;这3组的PI3K基因的水平分别为1.19±0.18,1.79±0.29和1.27±0.17。上述指标:模型组与正常组相比,或实验组与模型相比,差异均有统计学意义(均P<0.05)。同时,大鼠气道平滑肌厚度、PI3K基因的水平与FVC、FEV0.3呈负相关(均P<0.05)。结论阻断PI3K信号通路可以改善COPD大鼠肺功能及气道重塑,提示其可能参与了大鼠COPD发病过程。Objective To study the effect and mechanism of inhibitors of phosphoinositide 3-kinases(PI3 K)on chronic obstructive pulmonary disease(COPD)rats.Methods According to the random principle,Wistar rats were divided into three groups:normal group,model group and experimental group,12 rats in each group.COPD rat model was established through instilling the rats in 2000μL endotoxin(mass concentration:1μg·μL^-1),and then the rats were placed in 5%smoked in cigarette smoke for 0.5 h·d^-1.The rats in experimental group was intraperitoneally injected with LY294002(50μL)at a dose of 1.5 mg·kg^-1 at 1 h before each smoke.The rats in model group and normal group were injected intraperitoneally with normal saline before smoking.After modeling,the lung function-related indexes[forced vital capacity(FVC),forced expiratory volume in 0.3 s(FEV0.3)],the thickness of bronchial airway smooth muscle and the level of PI3K mRNA of rat airway smooth muscle cells were measured.Results FEV0.3 in normal group,model group,and experimental group were(6.13±0.76),(3.51±0.34)and(5.15±0.59)mL;FVC in the three groups were(7.39±0.52),(5.61±0.48)and(6.88±0.50)mL;the thickness of the smooth muscle in the three groups were(10.31±0.61),(19.80±1.53)and(14.40±0.64)μm2·μm^-1;the expression levels of PI3 K mRNA in the three groups were 1.19±0.18,1.79±0.29 and 1.27±0.17.Compared between with model group and normal group,or experimental group and model group,the differences of the factors were statistically significant(all P<0.05).The airway smooth muscle thickness and PI3 K mRNA levels were negatively correlated with FVC,FEV0.3(all P<0.05).Conclusion Blocking the PI3 K signaling pathway can improve lung function and airway remodeling in COPD rats,suggesting that it may be involved in the pathogenesis of COPD in rats.

关 键 词：慢性阻塞性肺疾病 磷脂酰肌醇3激酶 气道平滑肌 肺功能 

分 类 号：R974[医药卫生—药品]