蒙医温针下调脊髓背角小胶质细胞STAT3缓解大鼠脊髓损伤后坐骨神经痛

Down-regulation of STAT3 of spinal dorsal horn microglia through Mongolian medical warm acupuncture to relieve sciatica after spinal cord injury in rats

目的探讨蒙医温针缓解大鼠脊髓损伤后坐骨神经痛的意义。方法选择SPF级健康3月龄雄性Wistar大鼠,随机分为5组,正常对照组(Normal组,n=15),假手术组(Sham组,n=20),脊髓钝性损伤模型组(CNP组,n=30),STAT3 siRNA注射组(n=30),蒙医温针治疗组(n=30)。蒙医温针治疗组取鼠膝眼穴(髌韧带两侧凹陷处),髋穴(臀下横纹的中点)用特制银针治疗,比较各组大鼠行为学评分结果,统计蒙医温针治疗及鞘内注射STAT3 siRNA后大鼠行为学影响。结果CNP组大鼠造模后28 d时BBB评分高于造模后1、7、14、21 d时(P<0.05),CNP组大鼠造模后第3天开始后肢热缩足持续时间短于Sham组和Normal组(P=0.032)。CNP组鼠术后第3天,后肢机械缩爪阈值低于Sham组和Normal组(P=0.021)。蒙医温针组及STAT3 siRNA组大鼠TWD时间与Normal组、Sham组和空载病毒组相比显著降低(P<0.01),MWT显著升高(P<0.01),BBB评分显著升高(P<0.01),蒙医温针治疗后,造模后第7天、第14天和第28天脊髓STAT3表达均显著降低(P<0.01),蒙医温针组及STAT3 siRNA组STAT3mRNA表达显著低于Normal组、Sham组和空载病毒组(P<0.01)。结论小胶质细胞内STAT3信号转导通路的激活可能为脊髓损伤后中枢性坐骨神经痛的发病机制之一,蒙医温针治疗可能通过阻断脊髓背角小胶质细胞内STAT信号转导通路活性发挥临床作用。

Objective To explore the significance of Mongolian medical warm acupuncture in relieving sciatica after spinal cord injury in rats.Methods SPF healthy male Wistar rats aged 3 months were selected and randomly divided into five groups,namely the normal control group(normal group,n=15),sham operation group(sham group,n=20),spinal cord blunt injury model group(CNP group,n=30),STAT3 siRNA injection group(n=30)and Mongolian medical warm acupuncture treatment group(n=30).In Mongolian medical warm acupuncture treatment group,the knee-eye points(the depressions on both sides of the patellar ligament)and the hip points(the midpoint of the gluteal transverse stripes)were taken and treated with special silver needles.The results of behavioral scores of rats in each group were compared,and the behavioral effects of rats after Mongolian medical warm acupuncture treatment and intrathecal injection of STAT3 siRNA were counted.Results The BBB score of rats in CNP group on 28th day after modeling was higher than that on 1st,7th,14th and 21st day after modeling(P<0.05),and paw withdrawal thermal duration in CNP group from the 3rd day after modeling was shorter than that in sham group and normal group(P=0.032).On the 3rd day after operation,mechanical induction foot threshold in CNP group was lower than that in sham group and normal group(P=0.021).Compared with normal group,sham group and the airborne bacteria,in Mongolian medical warm acupuncture treatment group and STAT3 siRNA injection group the TWD time was significantly decreased(P<0.01),while MWT was significantly increased(P<0.01)and BBB score was significantly increased(P<0.01),and after Mongolian medical warm acupuncture treatment the expression of STAT3 in spinal cord was significantly decreased on the 7th,14th and 28th day after the modeling(P<0.01).The expression of STAT3 mRNA in the Mongolian medical warm acupuncture treatment group and STAT3siRNA injection group was significantly lower than that in normal group,sham group and the airborne bacteria.Conclusion The activation of STAT3 signal transduction pathway in microglia may be one of the pathogenesis of central sciatica after spinal cord injury,and Mongolian medical warm acupuncture treatment may play a clinical role by blocking the activity of STAT3 signal transduction pathway in microglia in spinal dorsal horn.