QIN Yang, NI Jinping, KANG Li, ZHONG Zhidong, WANG Liren, YIN Shuzhou. Mechanism of microRNA-31-5p regulating protein kinase Cε pathway in protection of rabbit spinal cord ischemia-reperfusion injury by remote ischemic preconditioning[J]. Journal of Clinical Medicine in Practice, 2022, 26(2): 11-17. DOI: 10.7619/jcmp.20214183
Citation: QIN Yang, NI Jinping, KANG Li, ZHONG Zhidong, WANG Liren, YIN Shuzhou. Mechanism of microRNA-31-5p regulating protein kinase Cε pathway in protection of rabbit spinal cord ischemia-reperfusion injury by remote ischemic preconditioning[J]. Journal of Clinical Medicine in Practice, 2022, 26(2): 11-17. DOI: 10.7619/jcmp.20214183

Mechanism of microRNA-31-5p regulating protein kinase Cε pathway in protection of rabbit spinal cord ischemia-reperfusion injury by remote ischemic preconditioning

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  • Received Date: October 24, 2021
  • Available Online: March 01, 2022
  • Published Date: January 27, 2022
  •   Objective  To investigate the role and mechanism of microRNA-31-5p (miR-31-5p) in the protection of rabbit spinal cord ischemia-reperfusion injury (SCIRI) by remote ischemic preconditioning (RIPC).
      Methods  A total of 60 Japanese white rabbits were divided into sham group, ischemia/reperfusion (I/R) group, RIPC group, RIPC+miR-NC group and RIPC+miR-31-5p mimic group, with 12 rabbits in each group. SCIRI model was established by clamping the abdominal aorta for 30 minutes, and the miR-31-5p overexpression model was constructed by intrathecal injection of miR-31-5p mimic plasmid. Except for the sham group and the I/R group, RIPC was performed in other groups one hour before the abdominal aorta closed. After 48 hours of reperfusion, the animals were evaluated for hindlimb motor function score and blood-spinal cord barrier (BSCB) permeability; Hematoxylin-Eosin (HE) staining was used to observe the morphological changes of spinal cord tissue; TUNEL was used to detect neuronal apoptosis in spinal cord tissue; reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression of miR-31-5p, protein kinase Cε (PKCε) and brain-derived neurotrophic factor (BDNF) in spinal cord tissue; Western Blot was used to detect the expression of PKCε and BDNF protein in spinal cord tissue.
      Results  Compared with the sham group, the hindlimb motor function score of the I/R group was significantly reduced, and the Evans blue (EB) content and neuron apoptosis rate were significantly increased (P < 0.05), and the number of spinal cord neurons was reduced, vacuolation was obvious, and nucleus pyknosis was observed; compared with the I/R group, the hindlimb motor function score, PKCε and BDNF mRNA and protein expression of RIPC group were significantly increased, and the EB content, neuronal apoptosis rate and miR-31-5p expression were significantly decreased (P < 0.05), the normal neurons increased significantly, a few cells had vacuolar degeneration, and nucleoli were obvious; upregulation of miR-31-5p expression with miR-31-5p mimic significantly weakened the protective effect of RIPC on rabbit SCIRI(P < 0.05).
      Conclusion  The expression of miR-31-5p decreases after RIPC, and it can increase the expression of BDNF in the spinal cord and relieve SCIRI by activating the PKCε protein.
  • [1]
    GU C J, LI L W, HUANG Y F, et al. Salidroside ameliorates mitochondria-dependent neuronal apoptosis after spinal cord ischemia-reperfusion injury partially through inhibiting oxidative stress and promoting mitophagy[J]. Oxid Med Cell Longev, 2020, 2020: 3549704.
    [2]
    PAN T Y, JIA P, CHEN N, et al. Delayed remote ischemic preconditioning ConfersRenoprotection against septic acute kidney injury via exosomal miR-21[J]. Theranostics, 2019, 9(2): 405-423. doi: 10.7150/thno.29832
    [3]
    KARIMIPOUR M, FARJAH G H, MOLAZADEH F, et al. Protective effect of contralateral, ipsilateral, and bilateral remote ischemic preconditioning on spinal cord ischemia reperfusion injury in rats[J]. Turk Neurosurg, 2019, 29(6): 933-939.
    [4]
    VELLANI V, SABATINI C, MILIA C, et al. CR4056, a powerful analgesic imidazoline-2 receptor ligand, inhibits the inflammation-induced PKCε phosphorylation and membrane translocation in sensory neurons[J]. Br J Pharmacol, 2020, 177(1): 48-64. doi: 10.1111/bph.14845
    [5]
    DIAZ R J, HARVEY K, BOLOORCHI A, et al. Enhanced cell volume regulation: a key mechanism in local and remote ischemic preconditioning[J]. Am J Physiol Cell Physiol, 2014, 306(12): C1191-C1199. doi: 10.1152/ajpcell.00259.2013
    [6]
    LIU Z G, LI Y, JIAO J H, et al. microRNA regulatory pattern in spinal cord ischemia-reperfusion injury[J]. Neural Regen Res, 2020, 15(11): 2123-2130. doi: 10.4103/1673-5374.280323
    [7]
    张燕, 张双霜, 胡霁, 等. 连接蛋白43在远端缺血预处理防治兔脊髓缺血再灌注损伤中对血脊髓屏障的作用及机制[J]. 微循环学杂志, 2018, 28(3): 12-19. doi: 10.3969/j.issn.1005-1740.2018.03.003
    [8]
    余奇劲, 田文华, 杨云朝. 远程缺血预处理对兔脊髓缺血再灌注损伤的保护作用及其机制[J]. 中国医药导报, 2018, 15(9): 8-12. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201809003.htm
    [9]
    黄锦秀. 远端缺血预处理对兔脊髓缺血再灌注损伤的保护作用及相关机制研究[D]. 武汉: 华中科技大学, 2017.
    [10]
    JING N, FANG B, WANG Z L, et al. Remote ischemia preconditioning attenuates blood-spinal cord barrier breakdown in rats undergoing spinal cord ischemia reperfusion injury: associated with activation and upregulation of CB1 and CB2 receptors[J]. Cell Physiol Biochem, 2017, 43(6): 2516-2524. doi: 10.1159/000484460
    [11]
    JIN L Y, LI J, WANG K F, et al. Blood-spinal cord barrier in spinal cord injury: a review[J]. J Neurotrauma, 2021, 38(9): 1203-1224. doi: 10.1089/neu.2020.7413
    [12]
    FANG B, LI X M, SUN X J, et al. Ischemic preconditioning protects against spinal cord ischemia-reperfusion injury in rabbits by attenuating blood spinal cord barrier disruption[J]. Int J Mol Sci, 2013, 14(5): 10343-10354. doi: 10.3390/ijms140510343
    [13]
    KITCHEN P, SALMAN M M, HALSEY A M, et al. Targeting aquaporin-4 subcellular localization to treat central nervous system edema[J]. Cell, 2020, 181(4): 784-799. e19. doi: 10.1016/j.cell.2020.03.037
    [14]
    黄锦秀, 解立杰, 胡霁. 远端缺血预处理对兔脊髓缺血再灌注损伤后血-脊髓屏障的保护作用及相关机制研究[J]. 中国医药导报, 2016, 13(21): 33-37. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201621008.htm
    [15]
    MARES J M, FOLEY L S, BELL M T, et al. Erythropoietin activates the phosporylated cAMP[adenosine 3′5′ cyclic monophosphate]response element-binding protein pathway and attenuates delayed paraplegia after ischemia-reperfusion injury[J]. J Thorac Cardiovasc Surg, 2015, 149(3): 920-924. doi: 10.1016/j.jtcvs.2014.11.011
    [16]
    WANG Y S, SU R B, LV G, et al. Supplement zinc as an effective treatment for spinal cord ischemia/reperfusion injury in rats[J]. Brain Res, 2014, 1545: 45-53. doi: 10.1016/j.brainres.2013.12.015
    [17]
    ZHUANG Q K, DAI C L, YANG L L, et al. Stimulated CB1 cannabinoid receptor inducing ischemic tolerance and protecting neuron from cerebral ischemia[J]. Cent Nerv Syst Agents Med Chem, 2017, 17(2): 141-150.
    [18]
    NEUMANN J T, THOMPSON J W, RAVAL A P, et al. Increased BDNF protein expression after ischemic or PKC Epsilon preconditioning promotes electrophysiologic changes that lead to neuroprotection[J]. J Cereb Blood Flow Metab, 2015, 35(1): 121-130. doi: 10.1038/jcbfm.2014.185
    [19]
    ZHANG L, GUO H, YUAN F, et al. Limb remote ischemia per-conditioning protects the heart against ischemia-reperfusion injury through the opioid system in rats[J]. Can J Physiol Pharmacol, 2018, 96(1): 68-75. doi: 10.1139/cjpp-2016-0585
    [20]
    SHEN X W, LEI J Q, DU L. miR-31-5p may enhance the efficacy of chemotherapy with Taxol and cisplatin in TNBC[J]. Exp Ther Med, 2020, 19(1): 375-383.
    [21]
    余奇劲, 杨云朝. 脊髓缺血性损伤时脑源性神经营养因子、丝氨酸/苏氨酸蛋白激酶ε蛋白和mRNA含量的变化及远程缺血预处理干预作用[J]. 临床外科杂志, 2018, 26(4): 307-309. doi: 10.3969/j.issn.1005-6483.2018.04.020
    [22]
    COSTA V, CARINA V, CONIGLIARO A, et al. miR-31-5p is a LIPUS-mechanosensitive microRNA that targets HIF-1α signaling and cytoskeletal proteins[J]. Int J Mol Sci, 2019, 20(7): E1569. doi: 10.3390/ijms20071569
    [23]
    TASENA H, BOUDEWIJN I M, FAIZ A, et al. miR-31-5p: a shared regulator of chronic mucus hypersecretion in asthma and chronic obstructive pulmonary disease[J]. Allergy, 2020, 75(3): 703-706. doi: 10.1111/all.14060
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