| 邵 英,李 洁,刘晓宇,毛培军,刘立栋,叶 欣,吴大方.糖尿病病理性神经痛大鼠坐骨神经中miR-133a的上调对疼痛阈值的影响及机制[J].现代生物医学进展英文版,2022,(14):2620-2624. |
| 糖尿病病理性神经痛大鼠坐骨神经中miR-133a的上调对疼痛阈值的影响及机制 |
| The Effect of up-regulation of miR-133a in the Sciatic Nerve of Rats with Diabetic Pathological Neuralgia on Pain Threshold and Its Mechanism |
| Received:February 05, 2022 Revised:February 28, 2022 |
| DOI：10.13241/j.cnki.pmb.2022.14.004 |
| 中文关键词: 糖尿病性神经疾病 坐骨神经 miR-133a-3p 雪旺氏细胞 |
| 英文关键词: Diabetic neuropathy Sciatic nerve miR-133a-3p Schwann cell |
| 基金项目:陕西省卫生健康委科研基金项目（2018D089）；陕西省自然科学基础研究计划一般项目（2019JM-422） |
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| 中文摘要: |
| 摘要 目的：探究糖尿病病理性神经痛大鼠坐骨神经中miR-133a的上调对疼痛阈值的影响及机制。方法：使用NGS测序和定量PCR分析糖尿病病理性神经痛大鼠坐骨神经中的相关 miRNA表达，预测潜在下游目标。使用miR-133a-3p转染的 RSC96细胞进行体外实验。使用微蛋白质印迹和蛋白质印迹以及免疫荧光分析验证miR-133a-3p的作用。使用miR-133a-3p拮抗剂分析miR-133a-3p与DNP之间的关联。结果：miR-133a-3p模拟物增加了RSC96细胞中VEGFR-2、p38αMAPK、TRAF-6和PIAS3的表达，并降低了NFκB p50和MKP3的表达（P＜0.05）。在正常大鼠中，AAV-miR-133a-3p通过神经内注射到坐骨神经中可诱导机械性异常性疼痛和p-p38 MAPK激活（P＜0.05）。在DM大鼠中，miR-133a-3p 拮抗剂给药可减轻DNP并下调p-p38磷酸化（P＜0.05）。结论：坐骨神经中miR-133a-3p的过度表达会引起这种疼痛，miR-133a-3p可能是患有神经性疼痛的患者的有用治疗靶点。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the effect and mechanism of up-regulation of miR-133a in the sciatic nerve of rats with diabetic pathological neuralgia on pain threshold. Methods: NGS sequencing and quantitative PCR were used to analyze the expression of related miRNAs in the sciatic nerve of diabetic pathological neuralgia rats to predict potential downstream targets. RSC96 cells transfected with miR-133a-3p were used for in vitro experiments. The effects of miR-133a-3p were verified using micro-western blotting, western blotting and immunofluorescence analysis. The association between miR-133a-3p and DNP was analyzed using miR-133a-3p antagonist. Results: miR-133a-3p mimic increased the expression of VEGFR-2, p38αMAPK, TRAF-6 and PIAS3 in RSC96 cells, and decreased the expression of NFκB p50 and MKP3(P＜0.05). In normal rats, AAV-miR-133a-3p can induce mechanical allodynia and p-p38 MAPK activation by intraneural injection into the sciatic nerve(P＜0.05). In DM rats, administration of miR-133a-3p antagonists can reduce DNP and down-regulate p-p38 phosphorylation(P＜0.05). Conclusion: The overexpression of miR-133a-3p in the sciatic nerve can cause this pain, and miR-133a-3p may be a useful therapeutic target for patients with neuropathic pain. |
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