利拉鲁肽对2型糖尿病患者血清miRNA表达及相关细胞信号通路蛋白的影响  

Effects of liraglutide on miRNAs expression profile and related cell signaling pathways in T2DM patients

作　　者：庄伟 王志强[1] 王正杰 安淑华[2] Zhuang Wei;Wang Zhiqiang;Wang Zhengjie;An Shuhua(Department of Pharmacy,Tangshan People′s Hospital,Tangshan 063300,China;Department of Endocrinology,Tangshan People′s Hospital,Tangshan 063300,China)

机构地区：[1]唐山市人民医院药剂科,063300 [2]唐山市人民医院内分泌科,063300

出　　处：《国际内分泌代谢杂志》2022年第4期307-311,共5页International Journal of Endocrinology and Metabolism

摘　　要：目的探讨利拉鲁肽对2型糖尿病(T2DM)患者血清miRNA表达谱及相关细胞信号通路蛋白水平的影响。方法选取唐山市人民医院于2020年10月至2021年10月期间收治的26例T2DM患者, 均接受利拉鲁肽治疗, 所有患者持续治疗3个月, 比对治疗前后血清miRNA变化情况, 采用Pearson相关分析hsa-miR29a-3p变化值与血清基质金属蛋白酶9(MMP-9)、转化生长因子(TGF)-β1变化值的相关性。对治疗前后表达水平变化差异显著的miRNA行基因本体论(GO)和KEGG通路富集分析, 以及miRNA-mRNA网络分析。结果治疗后患者的糖化血红蛋白A1c(HbAlc)、空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-C)、MMP-9以及TGF-β1水平均明显降低, 而高密度脂蛋白-胆固醇(HDL-C)水平明显增加(P均<0.05)。治疗后hsa-miR1-3p、hsa-miR21-5p、hsa-miR29a-3p、hsa-miR30c-5p、hsa-miR133a-5p、hsa-miR500-5p、hsa-mi6806-5p均明显降低(P均<0.05), 其中hsa-miR29a-3p降低程度最明显(P<0.001)。Pearson相关分析显示hsa-miR29a-3p变化值与MMP-9、TGF-β1变化值均呈正相关(r=0.638, 0.586), 差异有统计学意义(P均<0.05)。GO分析结果显示:胶原分解代谢过程、轴突延伸以及细胞黏附占生物过程前3位。细胞组分中内质网腔、突触后密度以及细胞连接占据前3位。分子功能中Rho GTPase结合、细胞外基质结构成分、磷脂酰肌醇3磷酸结合占据前3位。KEGG分析显示:差异表达基因主要富集于晚期糖基化终末产物受体信号通路、肿瘤坏死因子信号通路、Wnt信号通路(P均<0.05)。miRNA-mRNA网络分析显示差异表达miRNA对应244个靶基因mRNA。结论 T2DM患者经利拉鲁肽治疗后, 血清hsa-miR29a-3p等与炎症、胶原分解代谢过程相关的miRNA表达下调, 可能有利于减少患者心肌纤维化。Objective To investigate the effects of liraglutide on serum miRNA expression profiles and related cell signaling pathways in patients with type 2 diabetes mellitus(T2DM).Methods A total of 26 T2DM patients admitted to Tangshan People′s Hospital from October 2020 to October 2021 were selected,all received liraglutide treatment for 3 months.The changes of serum miRNA before and after treatment were compared,and the correlation between the changes of hsa-miR29a-3p and the changes of MMP-9 and TGF-β1 were analyzed by Pearson correlation.Gene ontology(GO)and KEGG pathway enrichment analysis,and miRNA-mRNA network analysis were performed for miRNAs with significant differences.Results After treatment,the levels of HbAlc,FPG,TG,TC,LDL-C,MMP-9,and TGF-β1 were significantly decreased,while the level of HDL-C was significantly increased(all P<0.05).After treatment,hsa-miR1-3p,hsa-miR21-5p,hsa-miR29a-3p,hsa-miR30c-5p,hsa-miR133a-5p,hsa-miR500-5p,and hsa-mi6806-5p were significantly decreased(all P<0.05),among which hsa-miR29a-3p decreased most significantly(P<0.001).Pearson correlation analysis showed that the change of hsa-miR29a-3p was positively correlated with the changes of MMP-9 and TGF-β1(r=0.638,0.586),and the difference were statistically significant(all P<0.05).The results of GO analysis showed that collagen catabolism,axon extension and cell adhesion accounted for the top three biological processes.The endoplasmic reticulum lumen,postsynaptic density,and cell junctions occupied the top three positions in cellular components.Among the molecular functions,Rho GTPase binding,extracellular matrix structural components,and phosphatidylinositol 3 phosphate binding occupied the first three positions.KEGG analysis showed that the differentially expressed genes were mainly enriched in the advanced glycation end product receptor signaling pathway,tumor necrosis factor signaling pathway and Wnt signaling pathway in diabetic complications(all P<0.05).miRNA-mRNA network analysis showed that the differentially expressed

关 键 词：利拉鲁肽 细胞信号通路 2型糖尿病 MIRNAS 

分 类 号：R587.1[医药卫生—内分泌]