GLP-1受体在脂多糖诱导的大鼠急性肺损伤中的作用及其机制  

Role of glucagon-like peptide-1 receptor in lipopolysaccharide-induced acute lung injury in rats and its mechanism

作　　者：段智[1] 邓加雄 雷小保[1] 李涛[1] DUAN Zhi;DENG Jia-Xiong;LEI Xiao-Bao;LI Tao(Critical Care Unit,First People′s Hospital of Chenzhou,Chenzhou 423000,Hunan Province,China)

机构地区：[1]郴州市第一人民医院重症医学科,湖南郴州423000

出　　处：《中华老年多器官疾病杂志》2020年第10期773-777,共5页Chinese Journal of Multiple Organ Diseases in the Elderly

基　　金：湖南省自然科学基金(2018JJ3015,2018JJ6004,2019JJ40010);郴州市科技计划(zdyf201924);郴州市第一人民医院院内项目(N2019-057)。

摘　　要：目的研究glucagon like peptide-1(GLP-1)受体在急性肺损伤(ALI)中的作用及相关机制。方法通过气管内注射脂多糖(LPS)法建立ALI模型。采用随机数表法将30只大鼠随机分为5组,每组6只。对照组大鼠建立假模型后接受生理盐水(NS)处理;空白药物组大鼠建立假模型后接受GLP-1受体激动剂利拉鲁肽(2 mg/kg)处理;模型组大鼠建立ALI模型后接受NS处理;治疗组大鼠建立ALI模型后接受利拉鲁肽(2 mg/kg)处理;抑制剂组大鼠建立ALI模型后接受利拉鲁肽(2 mg/kg)及自噬抑制剂3-methyladenine(3MA,10 mg/kg)处理。蛋白免疫印迹实验法检测各组大鼠肺中LC3II、Beclin-1、P62、Bax、Bcl-2蛋白的表达。采用TUNEL染色法检测细胞凋亡。应用SPSS 20.0软件进行数据处理。组间比较采用单因素方差分析和LSD多重比较。结果模型组LC3II、Beclin-1及P62表达分别为100.0%±5.3%、100.0%±5.6%、100.0%±6.1%,治疗组中LC3II及Beclin-1表达分别显著增加至214.0%±12.3%及329.0%±33.8%,P62表达显著下降至50.0%±7.0%(均P<0.01)。对照组肺损伤分数、湿/干重比(W/D)、Bax、Bcl-2及凋亡细胞分别为0.3±0.5、4.08±0.14、100.0%±7.0%、100.0%±3.6%、1.0±0.9,模型组肺损伤分数、湿/干重比(W/D)、Bax及凋亡细胞分别显著增加为4.6±0.8、4.83±0.23、284.0%±25.6%及42.5±8.2,Bcl-2显著下降至63.0%±6.2%(均P<0.001);与模型组比较,治疗组肺损伤分数、W/D、Bax、及凋亡细胞分别显著下降至2.5±1.0、4.42±0.15、198.0%±24.8%及17.0±3.4,Bcl-2显著增加至83.0%±5.3%(均P<0.01);与治疗组比较,抑制剂组肺损伤分数、W/D、Bax及凋亡细胞分别显著增加至4.3±0.8、4.77±0.25、277.0%±25.5%及39.5±6.2,Bcl-2下降至54.0%±5.0%(均P<0.01)。结论激活GLP-1受体可以显著改善脂多糖介导的急性肺损伤,其机制与其通过上调细胞自噬、进而减轻细胞凋亡有关。Objective To investigate the role of glucagon-like peptide-1(GLP-1)receptor in the lipopolysaccharide(LPS)-induced acute lung injury(ALI)and its mechanism.Methods ALI in rats was induced by intratracheal administration of LPS.A total of 30 rats were randomly divided into 5 groups,with 6 in each:the control group,sham model treated with normal saline(NS);the drug-blank group,sham model treated with liraglutide(2 mg/kg);the model group,ALI model treated with NS;the treatment group,ALI model treated with liraglutide(2 mg/kg);and the inhibitor group,ALI model treated with liraglutide(2 mg/kg)and 3-me thyladenine(10 mg/kg).Expression of LC3II,Beclin-1,P62,Bax and Bcl-2 were detected by Western blotting.Cell apoptosis was determined by the terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5-Triphosphate-Digoxigenin nick end labeling(TUNEL)assay.SPSS statistics 20.0 was used for data processing,and one-way analysis of variance and LSD multiple comparisons were used for comparison between groups.Results The expression of LC3II,Beclin-1 and P62 in the model group were 100.0%±5.3%,100.0%±5.6%,100.0%±6.1%,respectively.The expression of LC3II and Beclin-1 in treatment group increased respectively to 214.0%±12.3%and 329.0%±33.8%,and that of P62 decreased to 50.0%±7.0%(P<0.01).The control group had a lung injury score of 0.3±0.5,a wet/dry weight ratio(W/D)of 4.08±0.14,a Bax of 100.0%±7.0%,a Bcl-2 of 100.0%±3.6%,and apoptotic cells of 1.0±0.9.In the model group,the lung injury score,wet/dry weight(W/D),expression of Bax and apoptotic cells increased respectively to 4.6±0.8,4.83±0.23,284.0%±25.6%and 42.5±8.2,and expression of Bcl-2 decreased to 63.0%±6.2%(all P<0.01).Compared with the model group,the lung injury score,W/D,expression of Bax and apoptotic cells in treatment group decreased respectively to 2.5±1.0,4.42±0.15,198.0%±24.8%and 17.0±3.4,and the expression of Bcl-2 in treatment group increased to 83.0%±5.3%(all P<0.01).Compared with the treatment group,the lung injury score,W/D,expressi

关 键 词：急性肺损伤 G蛋白偶联受体 自噬 凋亡 

分 类 号：R563.8[医药卫生—呼吸系统]