miR-93-5p调控TXNIP/NLRP3通路对脑出血大鼠神经功能损伤的影响

doi:10.3969/j.issn.1006-6233.2025.12.04

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摘要 目的: 探讨miR-93-5p对脑出血(ICH)大鼠神经功能损伤及硫氧还蛋白相互作用蛋白/核苷酸结合寡聚化结构域样受体蛋白3(TXNIP/NLRP3)通路的影响。方法: 构建ICH大鼠模型,将造模成功大鼠随机分为模型组(ICH组)、miR-NC组、miR-93-5p mimics组、miR-93-5p mimics+pcDNA3.1组、miR-93-5p mimics+pcDNA-TXNIP组,每组18只,另取18只正常健康大鼠作为对照组(Control组);进行Longa评分;ELISA检测血清炎性因子水平;HE染色观察脑组织病理形态;TUNEL染色检测神经元凋亡;免疫组化检测Iba1表达;Western blot检测TXNIP/NLRP3通路相关蛋白表达;双荧光酶实验报告检测miR-93-5p与TXNIP的靶向关系。结果: ICH组较Control组脑组织结构破坏,细胞变性坏死,排列疏松紊乱,细胞核皱缩深染,间质水肿及炎性细胞浸润明显,Longa评分、脑组织含水量、IL-1β、IL-18水平及细胞凋亡率、Bax、C-caspase-9、C-caspase-3、Iba1、TXNIP、NLRP3、ASC、C-caspase-1表达升高(P<0.05);miR-93-5p mimics组较miR-NC组脑组织病理损伤减轻,Longa评分、脑组织含水量、IL-1β、IL-18水平及细胞凋亡率、Bax、C-caspase-9、C-caspase-3、Iba1、TXNIP、NLRP3、ASC、C-caspase-1表达降低(P<0.05);miR-93-5p mimics+pcDNA3.1组较miR-93-5p mimics+pcDNA-TXNIP组组脑组织病理损伤加重,Longa评分、脑组织含水量、IL-1β、IL-18水平及细胞凋亡率、Bax、C-caspase-9、C-caspase-3、Iba1、TXNIP、NLRP3、ASC、C-caspase-1表达升高(P<0.05);另外Starbase网站预测及双荧光素酶实验报告显示,miR-93-5p与TXNIP之间存在靶向关系。结论: miR-93-5p可对ICH大鼠神经功能损伤发挥保护作用,与抑制TXNIP/NLRP3通路相关。

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关键词 ：脑出血, miR-93-5p, TXNIP/NLRP3通路, 神经功能损伤

Abstract：Objective: To investigate the impacts of miR-93-5p on neurological dysfunction and thioredoxin-interacting protein/nucleotide-binding oligomerization domain-like receptor protein 3 (TXNIP/NLRP3) pathway in rats with cerebral hemorrhage (ICH). Methods: An ICH rat model was constructed, and successfully modeled rats were randomly grouped into model group (ICH group), miR-NC group, miR-93-5p mimics group, miR-93-5p mimics+pcDNA3.1 group, and miR-93-5p mimics+pcDNA-TXNIP group, each with 18 rats. Additionally, 18 normal healthy rats served as control group. Longa rating was conducted. ELISA was used to test serum inflammatory factors. HE staining was used to observe the pathological morphology of brain tissue. TUNEL staining was performed to test neuronal apoptosis. Immunohistochemistry was performed to test Iba1. Western blot was used to detect TXNIP/NLRP3 pathway related proteins. The dual luciferase assay report was used to test the targeting relationship between miR-93-5p and TXNIP. Results: For control group, ICH group revealed clear structural damages to brain tissue, degeneration and necrosis of cells, loose and disordered arrangement, nuclear shrinkage and deep staining, conspicuous interstitial edema, and inflammatory cell infiltration, and the Longa score, brain tissue water content, IL-1β, IL-18, apoptosis rate, Bax, C-caspase-9, C-caspase-3, Iba1, TXNIP, NLRP3, ASC, and C-caspase-1 elevated (P<0.05). The miR-93-5p mimics group showed less pathological damage to brain tissue than the miR-NC group, and the Longa score, brain tissue water content, IL-1β, IL-18, apoptosis rate, Bax, C-caspase-9, C-caspase-3, Iba1, TXNIP, NLRP3, ASC, and C-caspase-1 reduced (P<0.05). The miR-93-5p mimics+pcDNA3.1 group showed more severe brain tissue pathological damage than the miR-93-5p mimics+pcDNA-TXNIP group, and the Longa score, brain tissue water content, IL-1β, IL-18, apoptosis rate, Bax, C-caspase-9, C-caspase-3, Iba1, TXNIP, NLRP3, ASC, and C-caspase-1 elevated (P<0.05). In addition, Starbase website predictions and dual luciferase assay reports indicated a targeted relationship between miR-93-5p and TXNIP. Conclusion: MiR-93-5p can exert a protective effect on neurological damage in ICH rats, which is related to the inhibition of TXNIP/NLRP3 pathway.

Key words： Intracerebral hemorrhage miR-93-5p TXNIP/NLRP3 pathway Neurological dysfunction

基金资助:河北省卫生健康委员会办公室年度医学科学研究课题,(编号:20240383)

通讯作者: 高建洲

引用本文:

安世恩, 赵欢, 周涛, 高鹏竹, 常祥平, 高建洲. miR-93-5p调控TXNIP/NLRP3通路对脑出血大鼠神经功能损伤的影响[J]. 河北医学, 2025, 31(12): 1955-1963.
AN Shi'en, ZHAO Huan, ZHOU Tao, et al. Effect of miR-93-5p on Neurological Dysfunction in Rats with Cerebral Hemorrhage by Adjusting TXNIP/NLRP3 Pathway. HeBei Med, 2025, 31(12): 1955-1963.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.12.04 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I12/1955

[1] Magid-Bernstein J,Girard R,Polster S,et al.Cerebral hemorrhage:pathophysiology,treatment,and future directions[J].Circ Res,2022,130(8):1204-1229.
[2] Puissant MM,Mayer SA,Goldstein JN.Emergency priorities in the treatment of cerebral hemorrhage:code-intracerebral hemorrhage[J].Neurol Clin,2025,43(1):127-139.
[3] Wang H,Cao X,Wen X,et al.Transforming growth factorβ1 functions as a competitive endogenous RNA that ameliorates intracranial hemorrhage injury by sponging microRNA935p[J].Mol Med Rep,2021,24(1):499-511.
[4] Ismael S,Patrick D,Salman M,et al.Verapamil inhibits TXNIP-NLRP3 inflammasome activation and preserves functional recovery after intracerebral hemorrhage in mice[J].Neurochem Int,2022,161(1):105423-105433.
[5] Hu L,Zhang H,Wang B,et al.MicroRNA-152 attenuates neuroinflammation in intracerebral hemorrhage by inhibiting thioredoxin interacting protein (TXNIP)-mediated NLRP3 inflammasome activation[J].Int Immunopharmacol,2020,80(1):106141-106151.
[6] 贾传宇,王舒阳,管海博.赤芍总苷对脑出血大鼠神经功能损伤的改善及对脑组织中Treg/Th17比例的影响[J].中西医结合心脑血管病杂志,2023,21(2):272-275.
[7] Cheng X,Ander BP,Jickling GC,et al.MicroRNA and their target mRNAs change expression in whole blood of patients after intracerebral hemorrhage[J].Cereb Blood Flow Metab,2020,40(4):775-786.
[8] Lan S,Zhou L,Wang Y,et al.miRNA profiling of circulating small extracellular vesicles from subarachnoid hemorrhage rats using next-generation sequencing[J].Front Cell Neurosci,2020,14(1):242-252.
[9] Yang R,Chen J,Xu B,et al.circ_2858 helps blood-brain barrier disruption by increasing VEGFA via sponging miR-93-5p during escherichia coli meningitis[J].Mol Ther Nucleic Acids,2020,22(1):708-721.
[10] Hua Y,Zhou L,Yang W,et al.Y-2 reduces oxidative stress and inflammation and improves neurological function of collagenase-induced intracerebral hemorrhage rats[J].Eur Pharmacol,2021,910(1):174507-174517.
[11] Gan H,Zhang L,Chen H,et al.The pivotal role of the NLRC4 inflammasome in neuroinflammation after intracerebral hemorrhage in rats[J].Exp Mol Med,2021,53(11):1807-1818.
[12] Zhu X,Yao Y,Guo M,et al.Sevoflurane increases intracellular calcium to induce mitochondrial injury and neuroapoptosis[J].Toxicol Lett,2021,336(1):11-20.
[13] Wang HB,Wang WQ,Wu QJ,et al.Negative allosteric modulator of mGluR1 improves long-term neurologic deficits after experimental subarachnoid hemorrhage[J].ACS Chem Neurosci,2020,11(18):2869-2880.
[14] Yang CJ,Li X,Feng XQ,et al.Activation of LRP1 ameliorates cerebral ischemia/reperfusion injury and cognitive decline by suppressing neuroinflammation and oxidative stress through TXNIP/NLRP3 signaling pathway in mice[J].Oxid Med Cell Longev,2022,2022(1):8729398-8729420.
[15] Zhang M,Zhou H,He R,et al.Up-regulating microRNA-214-3p relieves hypoxic-ischemic brain damage through inhibiting TXNIP expression[J].Mol Cell Biochem,2023,478(3):597-608.