蛋白激酶抑制剂LY333531对大鼠烟雾吸入性肺损伤氧化应激的影响  

Effect of protein kinase inhibitor LY333531 on oxidative stress in rats with smoke inhalation lung injury

作　　者：程浩 宋立成 奂剑波 陈丽娜 陈旭昕 韩志海[1,2] Cheng Hao;Song Licheng;Huan Jianbo(Navy Clinical College of Anhui Medical University,Beijing 100048;Dept of Respiratory and Critical Care Medicine,Navy General Hospital,Beijing 100048)

机构地区：[1]安徽医科大学海军临床学院,北京100048 [2]海军总医院呼吸与危重症医学科,北京100048

出　　处：《安徽医科大学学报》2019年第3期407-412,共6页Acta Universitatis Medicinalis Anhui

基　　金：军队后勤科研计划重点项目(编号:BHJ16J011)

摘　　要：目的探索蛋白激酶抑制剂(LY333531)对大鼠烟雾吸入后氧化应激的作用。方法 6～8周龄SD雄性SPF级大鼠40只,随机分为空白对照组、抑制剂对照组、烟雾吸入组和烟雾吸入+抑制剂组。抑制剂对照组大鼠和烟雾吸入+抑制剂组大鼠在烟雾吸入实验前1周按1 mg/(kg·d)腹腔注射LY333531。1周后,于自制产烟箱建立大鼠烟雾吸入性肺损伤模型。12 h后解剖,留取动脉血、肺组织和肺泡灌洗液。对各组大鼠进行湿干比(W/D)、肺泡灌洗液(BALF)蛋白浓度、丙二醛(MDA)、一氧化氮合酶(NOS)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和衔接蛋白(P66Shc)的检测,制作HE染色切片,在光学显微镜下观察肺组织病理学特点。结果与空白对照组和抑制剂对照组相比,烟雾吸入组大鼠肺组织W/D、肺泡灌洗液蛋白浓度均明显上升(P <0. 05);肺组织及血清中MDA、NOS浓度明显上升(P <0. 05); SOD、CAT活性明显下降(P <0. 05);衔接蛋白(P66Shc)及活化后的p-P66Shc表达明显增加;病理切片可见明显肺泡壁增厚、肺泡断裂、渗出、炎性细胞浸润等。与烟雾吸入组相比,烟雾吸入+抑制剂组大鼠肺组织W/D、肺泡灌洗液蛋白浓度均有所降低(P <0. 05);血清MDA、NOS有所降低(P <0. 05); SOD以及CAT活性增加(P <0. 05);衔接蛋白(P66Shc)及活化后的p-P66Shc表达减少;肺泡断裂、渗出、炎性细胞浸润等病理改变减轻。结论 LY333531能减轻大鼠烟雾吸入后的氧化应激效应,减轻氧化应激对机体的损伤。Objective To explore the effect of protein kinase inhibitor(LY333531)on oxidative stress after smoke inhalation in rats.Methods Forty SD male SPF rats,6~8 weeks old,were randomly divided into the blank control group,inhibitor control group,smoke inhalation group and smoke inhalation+inhibitor group.Rats in the inhibitor control group and the smoke inhalation+inhibitor group were intraperitoneally injected with LY333531 at a dose of 1 mg/(kg·d)for one week before smoke inhalation.Then,the smoke inhalation induced acute lung injury(SI-ALI)rat model was established in a smoking generator.After 12 hours,the rats were dissected and the arterial blood,lung tissue,and bronchoalveolar lavage fluid(BALF)were collected.The wet and dry ratio(W/D),protein concentration of BALF,malondialdehyde(MDA),nitric oxide synthase(NOS),superoxide dismutase(SOD),catalase(CAT)and adaptor protein(P66 Shc)were detected.Hematoxylin-Eosin staining was performed and the histopathological features of the lung were observed under a light microscope.Results Compared with the blank control group and the inhibitor control group,the W/D of lung tissue and the protein concentration of BALF was increased significantly(P<0.05);the MDA and NOS concentrations in lung tissue and plasma increased significantly(P<0.05);the SOD and CAT activity decreased significantly(P<0.05);The expression of adaptor protein(P66 Shc)and activated p-P66 Shc was significantly increased;obvious alveolar wall thickening,alveolar rupture,exudation,and inflammatory cell infiltration were observed in pathological sections after smoke inhalation.Compared with the smoke inhalation group,the W/D and BALF protein concentrations were decreased(P<0.05).MDA and NOS in serum were decreased(P<0.05);SOD and CAT activities were increased(P<0.05);the adaptor protein(P66 Shc)and activated p-P66 Shc expression was decreased,and alveolar rupture,exudation,and inflammatory cell infiltration were alleviated with LY333531 pretreatment.Conclusion LY333531 can alleviate the oxidative stress effect a

关 键 词：LY333531 烟雾吸入 氧化应激 肺损伤 

分 类 号：R563.9[医药卫生—呼吸系统]