Spinal cord injury (SCI) is involved with abnormal expression of miRNAs (miRs) which are responsible for some II^ry injury responses which include apoptosis, inflammation and oxidative stress. Mechanisms involving miRs induced apoptosis still needs to be investigated. In the present work we developed a rat model of SCI, followed by microarray analysis for expression of miRs at various time points after SCI. The locomotor activity was assessed by Basso, Beattie and Bresnahan score, lesion volume was analyzed by cresyl violet staining and TUNEL staining for extent of apoptosis at various time points of post SCI. Numbers of miRs were altered after 2 weeks of SCI among which miR-466c-3p was the most significantly down-regulated. Transfection with miR-466c-3p mimics caused overexpression of miR-466c-3p, also improvement in functional recovery, decrease in apoptosis of neuronal cells and lesion size was observed in SCI rats. The Luciferase assay suggested that miR-466c-3p suppressed the expression of Bcl-2 (apoptosis regulator). It was also evidenced that upon restoring the levels of Bcl-2 with the help of pc-DNA3-Bcl-2 halted the attenuating action of miR-466c-3p in hydrogen peroxide exposed N9 microglia cells. The findings suggested that miR-466c-3p may inhibit mitochondrial apoptotic pathway via blocking Bcl-2 and cleaved capase-9/-3in rats after SCI. Altogether, the results suggested that miR-466c-3p may exert attenuating effect on functional recovery and inhibit the apoptosis of neuronal cells via halting the mitochondrial apoptosis cascade in SCI rats indicating that miR-466c-3p can be attractive therapeutic candidate in treating SCI.

脊髓损伤（SCI）是参与miRNA的异常表达（的miR），其是负责一些II ^RY损伤反应包括凋亡，炎症和氧化应激。涉及miRs诱导凋亡的机制仍需要研究。在目前的工作中，我们建立了SCI的大鼠模型，然后进行了微阵列分析，以分析SCI后各个时间点的miR表达。通过Basso，Beattie和Bresnahan评分评估运动活性，通过甲酚紫染色和TUNEL染色分析病变体积，以评估SCI后各个时间点的细胞凋亡程度。在SCI 2周后，miR的数量发生了变化，其中miR-466c-3p的表达下调幅度最大。在SCI大鼠中观察到用miR-466c-3p模拟物转染引起miR-466c-3p的过表达，还改善了功能恢复，神经元细胞凋亡和病变大小。萤光素酶检测表明miR-466c-3p抑制了Bcl-2（细胞凋亡调节剂）的表达。也有证据表明，在pc-DNA3-Bcl-2的帮助下恢复Bcl-2的水平后，miR-466c-3p在过氧化氢暴露的N9小胶质细胞中的衰减作用停止了。这些发现表明，miR-466c-3p可能通过阻断SCI大鼠体内的Bcl-2和裂解的capase-9 / -3而抑制线粒体的凋亡途径。总之，结果表明，miR-466c-3p可能通过中止SCI大鼠的线粒体凋亡级联反应而对功能恢复发挥减弱作用，并抑制神经元细胞的凋亡，这表明miR-466c-3p可能是治疗SCI的有吸引力的候选治疗药物。也有证据表明，在pc-DNA3-Bcl-2的帮助下恢复Bcl-2的水平后，miR-466c-3p在过氧化氢暴露的N9小胶质细胞中的衰减作用停止了。这些发现表明，miR-466c-3p可能通过阻断SCI大鼠体内的Bcl-2和裂解的capase-9 / -3而抑制线粒体的凋亡途径。总之，结果表明，miR-466c-3p可能通过中止SCI大鼠的线粒体凋亡级联反应而对功能恢复发挥减弱作用，并抑制神经元细胞的凋亡，这表明miR-466c-3p可能是治疗SCI的有吸引力的候选治疗药物。也有证据表明，在pc-DNA3-Bcl-2的帮助下恢复Bcl-2的水平后，miR-466c-3p在过氧化氢暴露的N9小胶质细胞中的衰减作用停止了。这些发现表明，miR-466c-3p可能通过阻断SCI大鼠体内的Bcl-2和裂解的capase-9 / -3而抑制线粒体的凋亡途径。总之，结果表明miR-466c-3p可能通过停止SCI大鼠的线粒体凋亡级联反应而对功能恢复发挥减弱作用，并抑制神经元细胞的凋亡，这表明miR-466c-3p可能是治疗SCI的有吸引力的治疗候选药物。这些发现表明，miR-466c-3p可能通过阻断SCI大鼠体内的Bcl-2和裂解的capase-9 / -3而抑制线粒体的凋亡途径。总之，结果表明，miR-466c-3p可能通过中止SCI大鼠的线粒体凋亡级联反应而对功能恢复发挥减弱作用，并抑制神经元细胞的凋亡，这表明miR-466c-3p可能是治疗SCI的有吸引力的候选治疗药物。这些发现表明，miR-466c-3p可能通过阻断SCI大鼠体内的Bcl-2和裂解的capase-9 / -3而抑制线粒体的凋亡途径。总之，结果表明，miR-466c-3p可能通过中止SCI大鼠的线粒体凋亡级联反应而对功能恢复发挥减弱作用，并抑制神经元细胞的凋亡，这表明miR-466c-3p可能是治疗SCI的有吸引力的候选治疗药物。