鹿茸多肽对训练创伤致脊髓损伤模型大鼠的作用及机制  

Effect and Mechanism of Velvet Antler Polypeptide on Spinal Cord Injury Model Rats Induced by Training Trauma

作　　者：廖军锋 王虹 龙桂花 吕晓宇 苏建 LIAO Junfeng;WANG Hong;LONG Guihua;LYU Xiaoyu;SU Jian(Southern Theater General Hospital of the Chinese PLA,Guangzhou,Guangdong,China 510010;Guangdong Second Hospital of Traditional Chinese Medicine,Guangzhou,Guangdong,China 510095)

机构地区：[1]中国人民解放军南部战区总医院,广东广州510010 [2]广东省第二中医院,广东广州510095

出　　处：《中国药业》2023年第5期51-57,共7页China Pharmaceuticals

基　　金：广东省中医药局中医药科研项目[20201376]。

摘　　要：目的探讨鹿茸多肽(VAP)对训练创伤致脊髓损伤(SCI)模型大鼠的作用及机制。方法将48只SD雄性大鼠随机分为空白(Control)组、模型(SCI)组、阳性对照(MSI-1436)组及VAP低、中、高剂量组(20,40,60 mg/kg),各8只。适应性饲养2 d后,结扎坐骨神经复制SCI模型,MSI-1436组大鼠术后14 d鞘内注射4μg MSI-1436(溶于20μL生理盐水)1次(单次给药),并于术后14,15,16 d各给药1次(连续给药);VAP低、中、高剂量组大鼠术后14 d分别腹腔注射20,40,60 mg/kg VAP 1次(单次给药),并于术后15,16,17,18 d各给药1次(连续给药);Control组和SCI组大鼠均给予等量生理盐水。使用Von Frey纤维丝测量大鼠的机械痛觉阈值和热痛觉潜伏期;采用免疫印迹(Western blot)法测定大鼠脊髓中多聚嘧啶序列结合蛋白(PTB)、磷酸化c-Jun氨基端蛋白激酶(p-JNK)、磷酸化p38(p-p38)、磷酸化胞外信号调节激酶(p-ERK)及炎性因子肿瘤坏死因子-α(TNF-α)和白细胞介素1β(IL-1β)的蛋白表达水平;采用免疫荧光化学法检测脊髓中神经元特异性烯醇化酶(NSE)的蛋白表达水平。结果与SCI组比较,VAP中、高剂量组大鼠单次给药2.0,4.0,8.0 h时同侧足的机械痛觉阈值均显著升高,热痛觉潜伏期均显著延长(P<0.05);VAP中剂量组大鼠连续给药5 d时同侧足的机械痛觉阈值均显著升高,热痛觉潜伏期均显著延长(P<0.05);VAP低、中、高剂量组大鼠脊髓中p-p38,p-JNK,PTB,IL-1β,TNF-α的蛋白表达水平均显著降低(P<0.05);VAP中、高剂量组大鼠脊髓中NSE的蛋白表达水平显著降低(P<0.05)。结论VAP可能通过抑制PTB的表达发挥对SCI模型大鼠的神经性疼痛和神经炎症的治疗作用,并促进神经修复。Objective To investigate the effect and mechanism of velvet antler polypeptide(VAP)on the spinal cord injury(SCI)model rats induced by the training trauma.Methods A total of 48 male SD rats were randomly divided into the blank(Control)group,the model(SCI)group,the positive control(MSI-1436)group and the VAP low-,medium-and high-dose groups(20,40,60 mg/kg respectively),with eight rats in each group.After 2 d of adaptive feeding,the sciatic nerve was ligated to replicate the SCI model.The rats in the MSI-1436 group were intrathecally injected with 4μg MSI-1436(dissolved in 20μL normal saline)once on the 14th day after operation(single administration),and were administered once on the 14th,15th and 16th days after operation(continuous administration).The rats in the VAP low-,medium-and high-dose groups were intraperitoneally injected with 20,40,60 mg/kg of VAP once on the 14th day after operation(single administration),and were administered once on the 15th,16th,17th and 18th days after operation(continuous administration).The rats in the Control group and the SCI group were given the same amount of normal saline.Von Frey filaments were used to measure the mechanical pain threshold and thermal pain latency of rats.The Western blot was used to measure the expression levels of polypyrimidine tract-binding protein(PTB),phosphorylated c-Jun N-terminal kinase(p-JNK),phosphorylated p38(p-p38),phosphorylated extracellular signal-regulated kinase(p-ERK)and inflammatory factors including tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in the spinal cord of rats.The immunofluorescence chemistry method was used to measure the expression level of neuron-specific enolase(NSE)in the spinal cord of rats.Results Compared with those in the SCI group,the mechanical pain threshold of the ipsilateral foot increased significantly and the thermal pain latency prolonged significantly in the VAP medium-and high-dose groups at 2.0,4.0,8.0 h after single administration(P<0.05).Compared with those in the SCI group,the mechanical

关 键 词：鹿茸多肽 脊髓损伤 神经性疼痛 多聚嘧啶序列结合蛋白 促分裂原活化蛋白激酶 作用机制 

分 类 号：R932[医药卫生—生药学] R285.5[医药卫生—药学]