miR-146b调控ERK1/2-AP-1信号通路参与糖尿病并发脑梗死大鼠模型的分子机制研究  

Molecular Mechanism of miR-146b Regulating ERK1/2-AP-1 Signaling Pathway Involved in the Rat Model of Diabetes Complicated with Cerebral Infarction

作　　者：刘伶俐[1] 魏若宣 陈蔚[1] 孔彩霞[1] 刘志红 LIU Lingli;WEI Ruoxuan;CHEN Wei;KONG Caixia;LIU Zhihong(Department of Endocrinology,Wuhan No1.Hospital/Wuhan Hospital of Traditional Chinese and Western Medicine,Wuhan 430022,China;College of Traditional Chinese Medicine,Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]武汉市第一医院/武汉市中西医结合医院内分泌科,武汉430022 [2]新疆医科大学中医学院,乌鲁木齐830000

出　　处：《现代检验医学杂志》2025年第2期135-139,共5页Journal of Modern Laboratory Medicine

基　　金：湖北省卫健委课题研究项目(WJ2023M122),武汉市卫健委科研项目(WX18B01)。

摘　　要：目的探究miR-146b是否可通过调控细胞外调节蛋白激酶(ERK1/2)活化蛋白-1(AP-1)信号通路参与糖尿病并发脑梗死(DM-CI)大鼠的脑损伤过程。方法将80只SD大鼠随机分为假手术组、DM-CI组、低表达miR-146b组和抑制ERK1/2组,每组20只。美国国立卫生研究院卒中量表(NIHSS)评分衡量大鼠脑功能。RT-qPCR检测大鼠脑组织中miR-146b,ERK1/2,AP-1的mRNA水平;Western blotting检侧大鼠脑组织中ERK1/2,AP-1的蛋白水平;TTC染色检测大鼠脑梗死体积;H&E染色检测大鼠脑组织病理学变化。血糖仪检测大鼠随机血糖水平。结果与假手术组相比,DM-CI组大鼠脑组织中miR-146b,ERK1/2,AP-1的mRNA表达水平显著增加,差异具有统计学意义(t=10.86,15.62,9.87,均P<0.05);ERK1/2,AP-1的蛋白水平增加,差异具有统计学意义(t=11.18,23.81,均P<0.05);NIHSS评分、随机血糖水平增加(t=44.49,30.02,均P<0.05);脑梗死体积增加(t=51.05,P<0.05),脑组织结构紊乱且疏松,部分细胞周围间隙可见水肿。与DM-CI组相比,低表达miR-146b组大鼠脑组织中miR-146b,ERK1/2,AP-1mRNA表达水平减少,差异具有统计学意义(t=38.00,20.03,24.25,均P<0.05);ERK1/2,AP-1蛋白表达减少,差异具有统计学意义(t=12.30,26.70,均P<0.05);NIHSS评分减少、随机血糖水平减少,差异具有统计学意义(t=38.11,33.77,均P<0.05),脑梗死体积减少(t=16.70,P<0.05),脑组织损伤及水肿程度改善。抑制ERK1/2组大鼠脑组织中ERK1/2,AP-1的蛋白及mRNA表达水平减少,差异具有统计学意义(t=13.61~38.00,均P<0.05),大鼠NIHSS评分、随机血糖水平减少,差异具有统计学意义(t=16.48,26.61,P<0.05)。结论miR-146b可通过调控ERK1/2 AP-1通路参与DM-CI大鼠的脑功能结构损伤过程。Objective To explore whether miR-146b can participate in the brain injury process of diabetic rats with cerebral infarction(DM-CI)by regulating the extracellular regulatory protein kinase(ERK1/2)-activated protein-1(AP-1)signaling pathway.Methods 80 SD rats were randomly divided into sham operation group,DM-CI group,low miR-146b expression group and ERK1/2 inhibition group,with 20 rats in each group.The National Institutes of Health Stroke Scale(NIHSS)score measures brain function in rats.The mRNA levels of miR-146b,ERK1/2 and AP-1 in rat brain tissue were detected by RT-qPCR.Western blotting detected ERK1/2,AP-1 protein levels in rat brain tissue.TTC staining was used to detect cerebral infarction volume in rats.H&E staining was used to detect brain histopathological changes.Random blood glucose levels were detected by glucose meter in rats.Results Compared with sham operation group,mRNA expression levels of miR-146b,ERK1/2 and AP-1 in brain tissue of rats in DM-CI group were significantly increased,with statistically differences(t=10.86,15.62,9.87,all P<0.05).ERK1/2 and AP-1 protein levels increased,with statistically differences(t=11.18,23.81,P<0.05).NIHSS score increased and random blood glucose level increased(t=44.49,30.02,all P<0.05),and increased cerebral infarction volume(t=51.05,P<0.05),the structure of brain tissue was disorganized and loose,and edema can be seen in the pericellular space.Compared with the DM-CI group,the mRNA expression levels of miR-146b,ERK1/2 and AP-1 in the brain tissue of rats with low expression of miR-146b were decreased,with statistically differences(t=38.00,20.03,24.25,all P<0.05).the protein expression of EPK1/2 and AP-1 decreased,and the differences were statistically significant(t=12.30,26.70,all P<0.05).NIHSS score and random blood glucose level were decreased,with statistically differences(t=38.11,33.77,all P<0.05),cerebral infarction volume decreased(t=16.70,P<0.05),the degree of brain tissue in jury and edema was improved,and the expression levels of ERK1/2 and AP-1 pr

关 键 词：糖尿病并发脑梗死 微小RNA-146b 调控细胞外调节蛋白激酶 活化蛋白-1 

分 类 号：R-332[医药卫生]