抗神经生长因子抗体对大鼠慢性坐骨神经压迫损伤模型的脊髓胶质细胞激活的抑制作用

Anti-nerve Growth Factor Antibody Inhibits the Spinal Cord Glial Cell Activation in Rats Model of Chronic Constriction Injury

目的研究抗神经生长因子抗体(anti-NGF)蛛网膜下腔应用对大鼠坐骨神经病理性疼痛模型痛阈的影响,并观察其对该模型星形胶质细胞激活的影响.方法手术制作大鼠慢性坐骨神经压迫损伤(chronic constriction injury,CC)I模型.实验大鼠采用随机数字表法分为4组:CCI+anti-NGF组(n=8):手术后第7天开始每天单次腹腔注射anti-NGF(10 mg/kg)、CCI模型+生理盐水组(n=8):手术后第7天开始每天单次腹腔注射生理盐水、假手术给anti-NGF组(n=8)和假手术盐水组(n=8).各组均在术后隔天测定大鼠痛行为学观察术后15 d内大鼠机械和热痛阈的变化.各组在手术后15 d,使用4%多聚甲醛灌流后,进行免疫组化染色,观察大鼠脊髓L4～5节段星形胶质细胞标记物GFAP表达情况.结果手术盐水对照组的机械和热痛阈在3 d后出现明显下降,在术后第7天达到高峰期.术后第7天单次给予anti-NGF能短时间内拮抗CCI大鼠的机械和热痛阈下降,连续给予anti-NGF 7 d后可以使大鼠的机械和热痛阈持续显著高于CCI+盐水组.15 d时CCI+anti-NGF组大鼠脊髓L4-5节段的GFAP表达显著低于CCI+生理盐水组.结论腹腔注射anti-NGF能有效拮抗CCI大鼠模型机械和热痛阈的下降.连续注射anti-NGF可以显著的持续改善CCI大鼠模型的机械和热痛阈的下降.CCI+anti-NGF组脊髓GFAP表达显著低于CCI+生理盐水组,这可能与anti-NGF持续改善大鼠的痛行为有关.

Objective To investigate the effects of anti-nerve growth factor antibody(anti-NGF)on the pain behavior and the spinal astrocyte activation in rats model of chronic constriction sciatic nerve injury(CCI).Methods Chronic sciatic nerve compression injury(chronic constriction injury,CCI)model was prepared by surgery in rats.The experimental rats were randomly divided into four groups: the CCI + anti-NGF group(n = 8).rats were given daily single intraperitoneal injection of anti-NGF(10 mg/kg) at 7th day after surgery;the CCI model + saline group(n = 8):rats were given daily single intraperitoneal injection of saline at 7th day after surgery;sham operation anti-NGF group(n =8)and sham operation saline group(n =8).Mechanical and thermal pain behavior were observed in every another day after surgery within 15 days.15 days after surgery,rats in each group was perfused by 4% paraformaldehyde,the expression of astrocyte cell marker GFAP in rats'L4-5-segment spinal cord was observed by immunohistochemical staining.Results Within 3 days after surgery,the CCI model + saline group's mechanical and thermal pain threshold decreased significantly and reached its peak after 7 days.At 7th dayafter surgery,a single dose of anti-NGF antibody intraperitoneal injection shortly alleviated the mechanical and thermal pain threshold decrease in CCI rats,continuously injection of anti-NGF 7 days significantly improved the mechanical and thermal pain threshold of CCI rats,which was higher than rats in CCI + saline group.The spinal GFAP expression in CCI + anti-NGF group was significantly lower than the CCI + saline group at 15th day after surgery.Conclusions Intraperitoneal injection of anti-NGF antibody can effectively reverse the pain behavior of the CCI rat model.Continuous injection of anti-NGF can significantly improve the pain behavior in the CCI rat models.In the spinal cord of rats in CCI + anti-NGF group,GFAP expression is significantly lower than that of CCI + saline group,this may be related to continuous injection of anti-NGF.