[1]刘伶俐,魏若宣,陈 蔚,等.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[J].现代检验医学杂志,2025,40(02):135-139.[doi:10.3969/j.issn.1671-7414.2025.02.025]
 LIU Lingli,WEI Ruoxuan,CHEN Wei,et al.Molecular Mechanism of miR-146b Regulating ERK1/2-AP-1 Signaling Pathway Involved in the Rat Model of Diabetes Complicated with Cerebral Infarction[J].Journal of Modern Laboratory Medicine,2025,40(02):135-139.[doi:10.3969/j.issn.1671-7414.2025.02.025]
点击复制

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()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年02期
页码:
135-139
栏目:
论著
出版日期:
2025-03-15

文章信息/Info

Title:
Molecular Mechanism of miR-146b Regulating ERK1/2-AP-1 Signaling Pathway Involved in the Rat Model of Diabetes Complicated with Cerebral Infarction
文章编号:
1671-7414(2025)02-135-05
作者:
刘伶俐1魏若宣2陈 蔚1孔彩霞1刘志红1
(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)
Author(s):
LIU Lingli1WEI Ruoxuan2CHEN Wei1KONG Caixia1LIU Zhihong1
(1.Department of Endocrinology, Wuhan No1. Hospital / Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan 430022,China; 2. College of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi 830000,China)
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
DOI:
10.3969/j.issn.1671-7414.2025.02.025
文献标志码:
A
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。
Abstract:
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 protein and mRNA in brain tissue of rats inhibited by ERK1/2 were decreased,with statistically differences (t=13.61 ~ 38.00, all P<0.05), the NIHSS score of rats was decreased, and the random blood glucose level was decreased,with statistically differences (t=16.48, 26.61, all P<0.05). Conclusion MiR-146b may be involved in brain functional and structural damage in DM-CI rats by regulating ERK1/2-AP-1 signaling pathway.

参考文献/References:

[1] CLOETE L. Diabetes mellitus: an overview of the types, symptoms, complications and management[J].Nursing Standard , 2022, 37(1): 61-66.
[2] BALOOCH HASANKHANI M, MIRZAEI H, KARAMOOZIAN A. Global trend analysis of diabetes mellitus incidence, mortality, and mortality-to-incidence ratio from 1990 to 2019[J]. Scientific Reports, 2023, 13(1): 21908.
[3] XIA Mingyu, YE Zankai, SHI Yanfeng, et al. Curcumin improves diabetes mellitus-associated cerebral infarction by increasing the expression of GLUT1 and GLUT3[J].Molecular Medicine Reports, 2018, 17(1): 1963-1969.
[4] L? Yifei, XI Yujie, ZHANG Liu, et al. Cerebral ischemia-induced gene expression changes in diabetic mice from acute to subacute stage [J]. Brain Research, 2024, 1825: 148737.
[5] ZHOU Hengjun, WANG Xiaoyi, WANG Liqing, et al. Interfering TRIB3 protects the blood brain barrier through PI3K/Akt pathway to alleviate cerebral ischemiareperfusion injury in diabetes mellitus mice[J], Chemico-Biological Interactions, 2024, 387: 110807.
[6] TAHERI M, EGHTEDARIAN R, GHAFOURIFARD S, et al. Non-coding RNAs and type 2 diabetes mellitus[J]. Archives of Physiology and Biochemistry, 2023, 129(2): 526-535.
[7] SUI Miao, JIANG Xiaofei, SUN Hongping, et al. Berberine ameliorates hepatic insulin resistance by regulating microRNA-146b/SIRT1 pathway [J].Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy, 2021, 14: 2525-2537.
[8] YANG Ren, ZENG Chen. Protective effects of miR-146b in cerebral infarction via targeting SIRT1/FOXO1 signaling pathway[J]. Cellular and Molecular Biology(Noisy-le-Grand, France), 2023, 69(12): 156-162.
[9] LY H T, PHAM K D, LE P H, et al. Pharmacological properties of Ensete glaucum seed extract: novel insights for antidiabetic effects via modulation of oxidative stress, inflammation, apoptosis and MAPK signaling pathways[J].Journal of Ethnopharmacology,2024, 320: 117427.
[10] ZHOU Chaoxi, WANG Fujun, MA Hongfang, et al. Silencing of FOS-like antigen 1 represses restenosis via the ERK/AP-1 pathway in type 2 diabetic mice[J]. Diabetes & Vascular Disease Research, 2021, 18(6): 14791641211058855.
[11] BAI Fei, HU Nan, YANG Ran, et al. Tongmai granules improve rat hippocampal injury by regulating TLR4/MyD88/AP-1 signaling pathway[J]. Journal of Ethnopharmacology, 2022, 285: 114874.
[12] ZABLOCKA B, DLUZNIEWSKA J, ZAJAC H, et al. Opposite reaction of ERK and JNK in ischemia vulnerable and resistant regions of hippocampus: involvement of mitochondria[J]. Molecular Brain Research, 2003, 110(2): 245-252.
[13] GHAFOURI-FARD S, SHOOREI H, TAHERI M. Role of non-coding RNAs in the pathogenesis of endometriosis [J] .Frontiers in Oncology, 2020, 10: 1370.
[14] 颜海峰, 吴小红, 林欲庆, 等.miR-582-5p 靶向调控FOXO1 对新生大鼠缺血缺氧性脑病神经元损伤的影响[J]. 天津医药,2024,52(4):356-361. YAN Haifeng, WU Xiaohong, LIN Yuqing, et al. Effect of miR-582-5p targeting regulation of FOXO1 on neuronal damage in neonatal rats with hypoxic ischemic encephalopathy [J]. Tianjin Medical Journal, 2024, 52(4): 356-361.
[15] SUN Yaoxiang, TAO Qing, WU Xueqin, et al. The utility of exosomes in diagnosis and therapy of diabetes mellitus and associated complications[J]. Frontiers in Endocrinology, 2021, 12: 756581.
[16] ZHANG Limei, WU Yanhui, QIU Lili, et al. Elevated levels of serum β2-glycoprotein I/oxidized low-density lipoprotein complexes are associated with cerebral infarction in patients with type 2 diabetes mellitus [J].Medical Science Monitor, 2018, 24: CLR1232-1240.
[17] HUTNY M, HOFMAN J, ZACHURZOK A, et al. MicroRNAs as the promising markers of comorbidities in childhood obesity-a systematic review[J]. Pediatric Obesity, 2022, 17(6): e12880.
[18] CUI Xianwei, YOU Lianghui, ZHU Lijun, et al. Change in circulating microRNA profile of obese children indicates future risk of adult diabetes. [J].Metabolism, 2018, 78: 95-105.
[19] 沈伟兴, 汤佳瑾, 傅鹏.2 型糖尿病肾病患者外周血micorRNA-155 水平与肾小球滤过率的相关性研究[J]. 现代检验医学杂志, 2022,37(1):12-16. SHEN Weixing, TANG Jiajin, FU Peng. Correlation between microRNA-155 level in peripheral blood and glomerular filtration rate in patients with type 2 diabetic nephropathy[J]. Journal of Modern Laboratory Medicine, 2022, 37(1): 12-16.
[20] TSAI T F, LIN Jifan, LIN Y C, et al. Cisplatin contributes to programmed death-ligand 1 expression in bladder cancer through ERK1/2-AP-1 signaling pathway[J].Bioscience Reports, 2019, 39(9): BSR20190362.
[21] 李阳, 包刚.LncRNA UCA1 介导Raf/MEK/ERK 信号通路调控乳腺癌细胞生物学作用的机制研究[J].现代检验医学杂志,2022,37(6):40-45. LI Yang, BAO Gang. Mechanism of lncRNA UCA1 mediating Raf/MEK/ERK signaling pathway to regulate the biological effects of breast cancer cells[J]. Journal of Modern Laboratory Medicine, 2022, 37(6): 40-45.
[22] LI Xiaohong, XIE Zhouxi, ZHOU Qian, et al. TGN-020 alleviate inflammation and apoptosis after cerebral ischemia-reperfusion injury in mice through glymphatic and ERK1/2 signaling pathway[J]. Molecular Neurobiology, 2024, 61(2): 1175-1186.
[23] MOHAMMED R A, SAYED R H, EL-SAHAR A E, et al. Insights into the role of pERK1/2 signaling in postcerebral ischemia reperfusion sexual dysfunction in rats[J].European Journal of Pharmacology, 2022, 933: 175258.
[24] MA Huike, YAO Wentao, PENG Bing, et al. Mercury-containing preparations attenuate neutrophil extracellular trap formation in mice and humans through inhibiting the ERK1/2 pathway[J]. Journal of Ethnopharmacology, 2024, 321: 117421.
[25] TAN Yongshun, CAO Huaimin, LI Qingfei, et al. The role of transcription factor Ap1 in the activation of the Nrf2/ARE pathway through TET1 in diabetic nephropathy[J].Cell Biology International, 2021, 45(8): 1654-1665.
[26] PHUONG N T T, KIM S K, IM J H, et al. Induction of methionine adenosyltransferase 2A in tamoxifen-resistant breast cancer cells[J]. Oncotarget, 2016, 7(12): 13902-13916.

备注/Memo

备注/Memo:
基金项目:湖北省卫健委课题研究项目(WJ2023M122),武汉市卫健委科研项目(WX18B01)。
作者简介:刘伶俐(1983-),女,主治医师,研究方向:内分泌代谢,E-mail:menguanliao424056@163.com。
更新日期/Last Update: 2025-03-15