BDNF-trkB信号通路在氯胺酮治疗糖尿病神经病理性疼痛中的作用  

Role of BDNF-trkB signaling pathway in ketamine treating diabetic neuropathic pain

作　　者：宗剑[1] 杨春[1] 胡明珠[2] 周波[1] 季永[1] 

机构地区：[1]江南大学附属医院(无锡市第四人民医院)麻醉科,江苏无锡214062 [2]江南大学无锡医学院,江苏无锡214062

出　　处：《中国药理学通报》2016年第6期801-806,共6页Chinese Pharmacological Bulletin

基　　金：无锡市医学管理中心医学科研面上项目(No YGZXM1407)

摘　　要：目的研究脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)-酪氨酸受体激酶B(tyrosine receptor kinase B,trk B)信号通路在氯胺酮治疗糖尿病神经病理性疼痛中的作用。方法♂Wistar大鼠48只,3月龄,体质量200~250 g,采用随机数字表法,将其分为4组(n=12):正常对照组(C组)、生理盐水组(S组)、氯胺酮组(K组)及氯胺酮+ANA-12组(KA组)。S、K及KA组大鼠腹腔单次注射链脲菌素(STZ)65 mg·kg^(-1)构建糖尿病神经病理痛模型。28 d后,S、K及KA组大鼠分别连续7 d腹腔注射等容积生理盐水、氯胺酮10 mg·kg^(-1)及氯胺酮10 mg·kg^(-1)+ANA-12 0.5 mg·kg^(-1)。d 8,测定大鼠机械缩足痛阈(MWT),然后处死大鼠取腰段脊髓背根及大脑前额皮层。采用Western blot和高尔基染色检测BDNF、p-trk B/trk B、突触素(synaptophysin)及树突棘密度。结果与C组比较,S组大鼠MWT明显下降,且脊髓背根和前额皮层BDNF、p-trk B/trk B、突触素及树突棘密度均明显下降(P<0.05);与S组相比,K组大鼠MWT、各部位BDNF、p-trk B/trk B、突触素和树突棘密度均明显增加(P<0.05);与K组相比,KA组大鼠MWT明显下降,且各部位BDNF、p-trk B/trk B、突触素和树突棘密度均明显下调(P<0.05)。各部位BDNF与树突棘密度均呈现正相关(P<0.05)。结论氯胺酮治疗糖尿病神经病理性疼痛的机制与BDNF-trk B信号通路的激活有关。Aim To investigate the role of brain-derived neurotrophic factor( BDNF)- tyrosine receptor kinase B( trk B) signaling pathway in the therapeutic effects of ketamine on diabetic neuropathic pain. Methods Forty-eight Wistar rats,aged 3 months,weighing200 ~ 250 g,were equally randomized into 4 groups( n= 12) : control group( C group), saline group( Sgroup),ketamine group( K group) and ketamine +ANA-12 group( KA group). Rats in S,K and KA groups were intraperitoneally injected with a single of streptozotocin( STZ) 65 mg·kg^(-1)to construct diabetic neuropathic pain model. After twenty-eight days,rats in S,K and KA groups were intraperitoneally injected with saline, ketamine 10 mg·kg^(-1)and ketamine10 mg·kg^(-1)+ ANA-12 0. 5 mg·kg^(-1)for consecutive7 days, respectively. On the 8th day, mechanical withdrawal threshold( MWT) of rats was measured. After that,the rats were immediately sacrificed,and dorsal ganglion of lumbar spine and prefrontal cortex( PFC) were harvested for measuring BDNF,p-trk B /trk B,synaptophysin and spine density by Western blot and glogi staining. Results Compared with C group,rats in S group significantly decreased MWT,BDNF,p-trk B / trk B,synaptophysin and spine density in dorsal ganglion and PFC( P < 0. 05). Compared with S group,rats in K group showed a significant increase of MWT,BDNF,p-trk B / trk B,synaptophysin and spinedensity in the all observed regions( P < 0. 05). On the contrary,rats in KA group showed a significant decrease of MWT and BDNF,p-trk B / trk B,synaptophysin and spine density as compared with K group in all regions( P < 0. 05). Furthermore,BDNF was positively correlated with spine density in all regions( P <0. 05). Conclusion BDNF- trk B signaling pathway mediates ketamine-induced therapeutic effects in diabetic neuropathic pain.

关 键 词：氯胺酮 神经病理性疼痛 脑源性神经营养因子 酪氨酸受体激酶 树突棘密度 突触素 

分 类 号：R-332[医药卫生] R322.81