微小RNA-195通过靶向抑制PH结构域富亮氨酸重复蛋白磷酸酶2表达参与香烟烟雾诱导急性肺损伤机制研究  

Mechanism of microRNA-195 participating in cigarette smoke-induced lung injury by targeting PHLPP2

作　　者：梁艳均[1] 吴桂全 漆勇 李静[1] LIANG Yanjun;WU Guiquan;QI Yong;LI Jing(Santai Hospital Affiliated to North Sichuan Medical College,Santai 621100,China)

机构地区：[1]川北医学院附属三台医院三台县人民医院,四川三台621100

出　　处：《陕西医学杂志》2023年第5期523-525,530,共4页Shaanxi Medical Journal

基　　金：四川省科技计划项目(2022KJ03)。

摘　　要：目的:探究miR-195通过靶向抑制PH结构域富亮氨酸重复蛋白磷酸酶2(PHLPP2)表达参与香烟烟雾诱导急性肺损伤的机制。方法:选择90只健康小鼠,均分为A、B、C三组,使用香烟烟雾暴露建立小鼠急性肺损伤模型,A组为正常对照组,B组为低剂量干预组,C组为高剂量干预组,干预后检测三组小鼠肺泡灌洗液中肿瘤坏死因子(TNF-α)、白介素-8(IL-8)及基质金属蛋白酶9(MMP-9)水平,对比三组小鼠肺泡灌洗液中白细胞、中性粒细胞计数,对比三组小鼠肺组织中髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)及谷胱甘肽(GSH)水平,最后检测三组小鼠肺组织中miR-195及PHLPP2蛋白表达量。结果:①肺泡灌洗液中TNF-α、IL-8及MMP-9水平C组>B组>A组,组间对比差异具有统计学意义(均P<0.05);②肺泡灌洗液中白细胞、中性粒细胞计数C组>B组>A组,组间对比差异具有统计学意义(均P<0.05);③肺泡灌洗液中MPO、SOD、GSH水平C组>B组>A组,组间对比差异具有统计学意义(均P<0.05);④肺组织中miR-195表达C组>B组>A组,PHLPP2蛋白表达C组<B组<A组,组间对比差异具有统计学意义(均P<0.05)。结论:香烟烟雾能够诱导小鼠肺组织出现炎性改变,其机制可能与miR-195过表达并抑制PHLPP2蛋白表达有关。Objective:To explore the mechanism of microRNA-195(miR-195)in cigarette smoke-induced lung injury by targeting inhibition of PHLPP2.Methods:Ninety healthy mice were divided into group A,B and C.The acute lung injury model of mice was established by exposure to cigarette smoke.Group A was normal control group,group B was low-dose intervention group,and group C was high-dose intervention group.After intervention,the levels of tumor necrosis factor(TNF-α),interleukin-8(IL-8)and matrix metalloproteinase 9(MMP-9)in the alveolar lavage fluid of the three groups were detected.Leukocyte and neutrophil counts in alveolar lavage fluid of three groups were compared.Levels of myeloperoxidase(MPO),superoxide dismutase(SOD)and glutathione(GSH)in lung tissues of three groups were compared.Finally,miR-195 and the expression of PHLPP2 protein of three groups were detected.Results:①The levels of TNF-α,IL-8 and MMP-9 in alveolar lavage fluid in group C were higher than those in group B and group A,and those in group B was higher than those in group A(all P<0.05).②The counts of white blood cells and neutrophils in alveolar lavage fluid in group C were higher than those in group B and group A,and those in group B was higher than those in group A(all P<0.05).③The levels of MPO,SOD and GSH in alveolar lavage fluid in group C were higher than those in group B and group A,and those in group B was higher than those in group A(all P<0.05).④The expression of miR-195 in lung tissue in group C was higher than that in group B and group A,and that in group B was higher than that in group A,and the expression of PHLPP2 protein was opposite(all P<0.05).Conclusion:Cigarette smoke can induce inflammatory changes in lung tissue of mice,which may be related to the overexpression of miRNA-195 and the inhibition of PHLPP2 protein expression.

关 键 词：微小RNA-195 PH结构域富亮氨酸重复蛋白磷酸酶2 香烟烟雾 肺损伤 蛋白表达 机制 

分 类 号：R563.9[医药卫生—呼吸系统]