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首页> 美国卫生研究院文献>American Journal of Translational Research >MicroRNA-155 mimics ameliorates nerve conduction velocities and suppresses hyperglycemia-induced pro-inflammatory genes in diabetic peripheral neuropathic mice
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MicroRNA-155 mimics ameliorates nerve conduction velocities and suppresses hyperglycemia-induced pro-inflammatory genes in diabetic peripheral neuropathic mice

机译：MicroRNA-155模拟改善糖尿病周围神经病小鼠的神经传导速度并抑制高血糖诱导的促炎基因

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Background: MicroRNA-155 (miR-155) regulates inflammatory cytokines, however its role in Diabetic neuropathy (DN) remains unexplored. Methods: A strain of mice (db/db) having type II diabetes were studied for expression of miR-155 in plasma and in sciatic nerves. The miR-155 mimic treated mice were studied for effect on motor and sensory nerve conduction velocities along with blood perfusion in sciatic nerves and response to thermal stimuli test. The mice were evaluated for density of blood vessels, quantity of intra-epidermal nerve fibers (IENF), diameters of axons & thickness of myelin sheath of sciatic nerves. Bioinformatics analysis was done to confirm target genes of miR-155. Results: The db/db mice showed significant suppression of miR-155 in sciatic nerves. The treatment of miR-155 mimic elevated levels of miR-155 in both sciatic nerves and plasma; it also enhanced the blood flow in sciatic nerves and velocities of conduction for both sensory and motor nerves. The treatment showed significant decrease in the threshold to thermal stimuli in db/db mice. A significant improvement in density of perfused blood vessels was observed, along with elevation of IENF and thickness of myelin and axon diameters of sciatic nerves. The treatment attenuated levels of TNF-α, iNOS, IL1-β and Ym1. Microarray analysis showed that the treatment decreased the expression of proinflammatory genes TRAF2 and Notch2, SORT1 and were identified as target by in silico studies. Conclusion: Treatment of miR-155 mimic in db/db mice attenuated DN, suppressed diabetic associated proinflammatory genes and confirmed miR-155 mimic as therapeutic strategy for treating DN.
机译：背景：MicroRNA-155（miR-155）调节炎性细胞因子，但其在糖尿病性神经病（DN）中的作用尚待探索。方法：研究了II型糖尿病小鼠的品系（db / db）在血浆和坐骨神经中的miR-155表达。研究了miR-155模仿小鼠对运动和感觉神经传导速度的影响以及坐骨神经的血液灌注和对热刺激试验的反应。评价小鼠的血管密度，表皮内神经纤维（IENF）数量，轴突直径和坐骨神经髓鞘厚度。进行了生物信息学分析以确认miR-155的靶基因。结果：db / db小鼠在坐骨神经中显示出对miR-155的显着抑制。 miR-155的治疗可模拟坐骨神经和血浆中miR-155的水平升高；它还增加了坐骨神经的血流量和感觉神经和运动神经的传导速度。治疗表明db / db小鼠的热刺激阈值显着降低。观察到灌注血管密度的显着改善，以及IENF升高，髓磷脂厚度和坐骨神经轴突直径。治疗减弱了TNF-α，iNOS，IL1-β和Ym1的水平。芯片分析表明，该治疗降低了促炎基因TRAF2和Notch2，SORT1的表达，并且被计算机研究鉴定为靶标。结论：db / db小鼠中miR-155模拟物的治疗可减轻DN，抑制糖尿病相关的促炎基因，并证实miR-155模拟物是治疗DN的治疗策略。

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