神经生长因子对老年退变性膝骨关节炎疼痛模型的影响

目的:探讨体外模型评价神经生长因子(nerve growth factor,NGF)抗体在膝骨关节炎(knee osteoarthritis,KOA)疼痛模型中的作用。方法:选取30只8周龄雄性SPF大鼠,分为空白组10只;其余20只行右膝关节单碘乙酸 (monoiodoacetate,MIA) 注射,制备骨性关节炎疼痛模型。造模成功后,再根据干预方法不同分为对照组(生理盐水腹腔注射)、治疗组(抗NGF 腹腔注射),每组10只。所有动物右膝关节进行荧光金 (fluorogold,FG) 逆行神经示踪剂注射。分别在治疗前,治疗后1、2周使用猫道步态分析系统评估步态。治疗后3周,从L₃-L₅水平切除右背根神经节(dorsal root ganglia,DRG),进行降钙素基因相关肽 (calcitonin gene-related peptide,CGRP) 免疫染色,并计算DRG数量。结果:在使用猫道系统的步态分析中,与空白组相比,对照组、治疗组占空比、摆动速度和触地面积比率明显降低(P<0.05);与对照组相比,治疗组占空比、摆动速度明显改善(P<0.05),触地面积比率与空白组比较,差异无统计学意义(P>0.05)。对照组中FG标记的DRG神经元数量高于治疗组和空白组(P<0.05);对照组CGRP表达上调,与治疗组比较,差异有统计学意义(P<0.05)。结论:腹腔注射抗 NGF抗体抑制了步态损伤和 DRG 神经元中CGRP 的上调。这些发现提示抗神经生长因子治疗可能对治疗膝关节疼痛有价值。NGF可能是治疗KOA疼痛的重要靶点。

Effect of nerve growth factor on elderly degenerative knee osteoarthritis pain

Objective To explore effect of nerve growth factor (NGF) antibody on knee osteoarthritis (KOA) pain model was evaluated by in vitro model. Methods Thirty male SPF rats aged 28-week-old were divided into blank group (10 rats with anesthesia only). The other 20 rats were with monoiodoacetate (MIA) on the right knee joint to establish pain model of OA,and were randomly divided into control group (injected intraperitoneal injection of normal saline) and treatment group (injected anti-NGF) intraperitoneal after successful modeling,and 10 rats in each group. All rats were received retrograde injection of fluorogold (FG) into the right knee joint. Gait was assessed using catwalk gait analysis system before treatment,1 and 2 weeks after treatment. Three weeks after treatment,right dorsal root ganglia (DRG) were excised on L₄-L₆ level,immunostained for calcitonin gene-related peptide (CGRP),and the number of DRGS was counted. Results In terms of gait analysis using cat track system,duty cycle,swing speed and print area ratio in control and treatment group were significantly reduced compared with blank group (P<0.05). Compared with control group,duty cycle and swing speed of treatment group were significantly improved (P<0.05),and there was no significant difference in print area ratio between treatment group and blank group (P>0.05). The number of FG-labeled DRG neurons in control group was significantly higher than that in treatment group and blank group (P<0.05). The expression of CGRP in control group was up-regulated,and differences were statistically significant compared with treatment group (P<0.05). Conclusion Intraperitoneal injection of anti-NGF antibody inhibited gait injury and upregulation of CGRP in DRG neurons. The results suggest that anti-nerve growth factor therapy may be of value in treating knee pain. NGF may be an important target for the treatment of knee OA pain.