艾塞那肽改善糖尿病小鼠症状的核心基因探究  

Exploring the core hub gene targeted by exenatide in improving symptoms of diabetes mellitus mice

作　　者：程优 刘影 房敬尧 甄若楠 朱黎娜 牛文彦[1] CHENG You;LIU Ying;FANG Jingyao;ZHEN Ruonan;ZHU Lina;NIU Wenyan(NHC Key Laboratory of Hormones and Development/Tianjin Key Laboratory of Metabolic Diseases/Chu Hsien-I Memorial Hospital&Tianjin Institute of Endocrinology/Tianjin Medical University,Tianjin 300134;Hebei International Travel Health Care Center/Shijiazhuang Customs District P.R.China,Shijiazhuang 050091;The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China)

机构地区：[1]天津医科大学朱宪彝纪念医院检验科/天津市内分泌研究所/国家卫健委激素与发育重点实验室/天津市代谢性疾病重点实验室,天津300134 [2]河北国际旅行卫生保健中心/石家庄海关口岸门诊部,河北石家庄050091 [3]天津中医药大学第二附属医院检验科,天津300250

出　　处：《生物技术》2024年第6期707-714,787,共9页Biotechnology

基　　金：国家自然科学基金面上项目(82270856);天津市医学重点学科(专科)建设项目(TJYXZDXK-032A);天津医科大学朱宪彝纪念医院科研基金资助项目(2019ZDKF08,ZXY-YJJ2021-3);天津中医药大学第二附属医院科研基金资助项目(QMJH202122)。

摘　　要：[目的]探究艾塞那肽治疗糖尿病的机制和靶基因。[方法]下载数据集筛选差异表达基因,构建疗效相关的共表达网络筛选加权基因,选取两组数据交集基因并使用蛋白互作网络确立核心基因,使用糖尿病模型小鼠验证核心基因。[结果]共获取15个交集基因,综合GO/KEGG功能分析以及cytoHubba评分,选择血清和糖皮质激素诱导的激酶-1(serum and glucocorticoid regulated protein kinase-1,SGK1)作为核心基因。治疗组小鼠7 w空腹血糖和体重[(19.03±3.20)mmol/L;(48.23±1.97)g]较安慰剂组[(25.62±2.01)mmol/L;(53.23±1.79)g]均降低(P<0.05);治疗组小鼠胰腺SGK1 mRNA和蛋白表达较安慰剂组降低(P<0.05),免疫组织化学染色显示治疗组小鼠胰腺组织结构相对完整,胰岛形态基本规则,较安慰剂组有明显改善,与生物信息学分析一致。[结论]艾塞那肽可通过抑制核心基因SGK1基因表达改善糖尿病小鼠血糖水平,保护胰腺组织。[Objective]To explore the potential molecular mechanisms and hub gene of exenatide in diabetes mellitus(DM).[Method]The study harnessed datasets and selected differentially expressed genes(DEGs),then calculated the weighted genes by construction of a co-expression network correlating to drug intervention,and screened the intersection genes in both groups.The core hub gene was identified via protein-protein interaction(PPI)network and this assumption was validated in DM mice.[Result]Bioinformatics analyses yielded 15 intersecting genes,through integrated GO/KEGG functional analysis and cytoHubba scoring,serum and glucocorticoid regulated protein kinase(SGK1)was selected as the core gene.Exenatide-trea-ted DM mice exhibited significant reductions in blood glucose and body weight[(19.03±3.20)mmol/L and(48.23±1.97)g,respectively]compared with those of the placebo group[(25.62±2.01)mmol/L and(53.23±1.79)g,respectively]at the 7th week,and the difference was statistically significant(P<0.05).The experimental group also demonstrated notable downregulation in both mRNA and protein expression of SGK1(P<0.05).Immunohistochemistry staining exhibited pancreatic tissue structure was relatively intact and the morphology of islets was basically normal in treatment group compared to the place-bo group.The animal experiment results were consistent with bioinformatic predictions.[Conclusion]Exenatide can improve blood glucose level and protect pancreatic tissue in DM mice by inhibiting the expression of core hub gene SGK1.

关 键 词：艾塞那肽 2型糖尿病 生物信息学 枢纽基因 血清和糖皮质激素诱导的激酶-1 加权基因共表达网络分析 基因本体论 差异表达基因 

分 类 号：R394.6[医药卫生—医学遗传学]