MicroRNA-136-5p靶向STAT3调控对脊髓损伤大鼠炎症因子的影响*

Effects of STAT3 targeting by microRNA136-5p on inflammatory factors in rats with spinal cord injury*

摘要:

目的 研究microRNA-136-5p（miR-136-5p）靶向信号转导和转录激活子3（STAT3）调控对脊髓损伤大鼠炎症因子的影响。方法 选取60只SD健康大鼠，随机分为对照组、脊髓损伤组、沉默组及过表达组，每组15只。将脊髓损伤组、沉默组、过表达组大鼠复制脊髓损伤模型，对照组在模型复制期间不做任何处理。无菌环境下将10?μl miR-136-5p慢病毒悬液（病毒滴度为108 TU/ml）注射于沉默组、过表达组大鼠脊髓损伤区。对照组、脊髓损伤组大鼠注射等量的生理盐水。使用BBB评分、联合行为评分法（CBS）对4组大鼠运动功能、脊髓神经功能进行评价，检测4组大鼠脊髓组织白细胞介素-6（IL-6）、白细胞介素-21（IL-21）、白细胞介素-23（IL-23）表达水平及STAT3、磷酸化STAT3（p-STAT3）蛋白相对表达量，以及IL-17 mRNA表达水平。结果 沉默组大鼠BBB评分高于脊髓损伤组和过表达组（P?<0.05）；沉默组大鼠CBS评分低于脊髓损伤组和过表达组（P?<0.05）。沉默组大鼠脊髓组织IL-6、IL-21、IL-23表达水平低于脊髓损伤组和过表达组（P?<0.05）。沉默组大鼠脊髓组织STAT3、p-STAT3蛋白相对表达量、IL-17 mRNA表达水平均低于对照组、脊髓损伤组及过表达组（P?<0.05）。结论 脊髓损伤后miR-136-5p沉默可抑制STAT3的表达，进而抑制炎症因子的过度表达，最终抑制脊髓炎症反应。

Abstract:

Objective To investigate the effects of microRNA-136-5p (miR-136-5p) targeting signal transducers and transcriptional activators 3 (STAT3) on inflammatory factors in rats with spinal cord injury. Methods Sixty SD healthy rats were randomly divided into control group, spinal cord injury group, silent group and over-expression group. Spinal cord injury group, silent group and over-expression group were used to establish spinal cord injury model. The control group was not treated during the modeling period. The lentiviral suspension of 10?μl miR-136-5p (viral titer 108 TU/ml) was injected into the spinal cord injury area of rats in silence group and overexpression group, and the rats in control group and spinal cord injury group were injected with the same amount of saline. The motor function and spinal nerve function of rats in four groups were evaluated by BBB score and combined behavioral score (CBS). The expressions of interleukin-6 (IL-6), interleukin-21 (IL-21), interleukin-23 (IL-23) and the relative expressions of STAT3, phosphorylated STAT3 (p-STAT3) protein and IL-17 mRNA in spinal cord of rats in four groups were detected. Results BBB score of silent group was higher than that of spinal cord injury group and overexpression group (P?