白细胞介素-4介导低强度运动对慢性坐骨神经缩窄性损伤小鼠的镇痛作用

Analgesic effect of low-intensity exercise induced by interleukin-4 on chronic constriction injury of sciatic nerve in mice

目的探讨低强度运动能否通过白细胞介素(IL)-4介导对慢性坐骨神经缩窄性损伤(CCI)小鼠发挥镇痛作用。方法雄性C57/BL6健康小鼠48只,采用随机数字表法分为6组(n=8):假手术/静坐组(SS组)、假手术/生理盐水/运动(SNE组)、假手术/抗IL-4/运动(SAE组)、CCI/静坐组(CS组)、CCI/生理盐水/运动组(CNE组)、CCI/抗IL-4/运动组(CAE组)。制备CCI模型,造模后第1-15天行低强度运动,SAE组和CAE组小鼠运动前30 min腹腔注射IL-4受体拮抗剂(IL-4Ra)50μg。造模后第3(T_(1))、7(T_(2))、11(T_(3))、15(T_(4))天进行行为学测试以分析小鼠痛觉过敏的差异。造模后第15天取小鼠损伤侧坐骨神经和腰段脊髓(L_(1)~L_(6)),采用ELISA法检测IL-4、IL-1Ra、IL-5、肿瘤坏死因子-α(TNF-α)、IL-1β、脑源性神经营养因子(BDNF)、β-神经生长因子(β-NGF)的表达水平。结果CNE组造模后T_(3)和T_(4)时的机械刺激缩足反射阈值(PWMT)和热刺激缩足反射潜伏期(PWTL)均高于CS组和CAE组(P<0.05);CNE组和CAE组坐骨神经和腰段脊髓的IL-4水平均高于CS组,差异有统计学意义(P<0.05);CNE组坐骨神经和腰段脊髓的IL-1Ra、IL-5水平均高于CS组和CAE组,TNF-α、IL-1β、BDNF、β-NGF水平均低于CS组和CAE组,差异有统计学意义(P<0.05)。结论低强度运动可能通过IL-4介导对CCI小鼠产生镇痛作用。

Objective To explore the analgesic effect of low-intensity exercise induced by interleukin(IL)-4 on chronic constriction injury of the sciatic nerve(CCI)mice.Methods A total of 48 male C57/BL6 mice were randomized into 6 groups(n=8):sham/sedentary group(SS group),sham/normal saline/exercise group(SNE group),sham/anti-IL-4/exercise group(SAE group),CCI/sedentary group(CS group),CCI/normal saline/exercise group(CNE group),CCI/anti-IL-4/exercise group(CAE group).After inducing CCI,mice were given low-intensity exercise from 1 to 15 days.For the SAE group and the CAE group,mice received 50μg of IL-4 receptor blocker(IL-4Ra)30 min before exercise through intraperitoneal injection.Behavioural tests were performed on the 3rd day(T_(1)),7th day(T_(2)),11th day(T_(3))and 15th day(T_(4))to analyze the difference of hyperalgesia.On the 15th day after CCI induction,the injured sciatic nerve and lumbar spinal cord(L_(1)-L_(6))of all mice were collected.The levels of IL-4,IL-1Ra,IL-5,TNF-α,IL-1β,brain-derived neurotrophic factor(BDNF)andβ-nerve growth factor(β-NGF)were detected by ELISA.Results The paw withdrawal mechanical threshold(PWMT)and paw withdrawal thermal latency(PWTL)values of the CNE group at T_(3) and T_(4) were higher than those of the CS group and CAE group(P<0.05);the IL-4 levels of the sciatic nerve and lumbar spinal cord in CNE group and CAE group were higher than those of CS group(P<0.05);the IL-1Ra and IL-5 levels of the sciatic nerve and lumbar spinal cord in CNE group were higher than those of CS group and CAE group(P<0.05);the TNF-α,IL-1β,BDNF andβ-NGF levels of the sciatic nerve and lumbar spinal cord of CNE group were lower than those of CS group and CAE group(P<0.05).Conclusion Low-intensity exercise exerts the analgesic effect on mice with chronic constriction injury of sciatic nerve through IL-4.