苯丁酸钠对紫杉醇诱导小鼠外周神经痛的镇痛作用  

Analgesic Effect of Sodium Phenylbutyrate on Paclitaxel-Induced Peripheral Neuralgia in Mice

作　　者：戴向荣 李小羿 殷雷 陈程 江万祥 钟玉婷 DAI Xiangrong;LI Xiaoyi;YIN Lei;CHEN Cheng;JIANG Wanxiang;ZHONG Yuting(Center of R&D,ZhaoKe Pharmaceutical(Guangzhou)Co.,Ltd.,Guangzhou 511462,China;Sichuan Gelin Taike Biologic Science and Technology Co.,Ltd.,Meishan 620020,China)

机构地区：[1]兆科药业(广州)有限公司研发中心,广东广州511462 [2]四川格林泰科生物科技有限公司,四川眉山620020

出　　处：《生物化工》2022年第5期8-12,共5页Biological Chemical Engineering

摘　　要：目的:通过紫杉醇诱导的小鼠外周神经痛(CIPN)模型评价苯丁酸钠对外周神经病变引起的痛觉过敏现象的改善作用。方法:试验共分为6个组(10只/组),分别为正常对照组、模型对照组、苯丁酸钠低(0.5 g/kg)、中(1.0 g/kg)、高(1.5 g/kg)剂量组和普瑞巴林组(5.0 mg/kg),首次给药定义为第1 d,连续给药30 d,在1 d、3 d、4 d、7 d给药1 h后腹腔注射紫杉醇(4.5 mg/kg)诱导小鼠外周神经痛产生。观察一般状态、体重、机械痛缩足阈值及光热痛缩足潜伏期等指标。结果:苯丁酸钠高、中剂量组给药后产生了一定的神经毒性(体温下降、嗜睡),对体重无明显影响;药物干预后,苯丁酸钠对机械痛缩足阈值(低、中、高剂量组)、光热痛缩足潜伏期(中、高剂量组)的影响与阳性药物普瑞巴林相似,具有良好的镇痛作用;低、中、高剂量组苯丁酸钠与阳性药物均轻微改善了紫杉醇引起的小鼠坐骨神经中有髓神经纤维的脱髓鞘程度。结论:苯丁酸钠具有明显的镇痛作用,后续仍需进一步探索最佳应用剂量。Objective:To evaluate the ameliorative effect of sodium phenylbutyrate on hyperalgesia caused by peripheral neuropathy in a paclitaxel-induced mouse model of peripheral neuralgia(CIPN).Methods:The experiment is divided into 6 groups(10 mice/group):normal control group,model control group,sodium phenylbutyrate low dose group(0.5 g/kg),medium dose group(1.0 g/kg),high dose group(1.5 g/kg)and pregabalin group(5.0 mg/kg),respectively.The date of the first dose is defined as the first day,continuous administration for 30 days,and intraperitoneal injection of paclitaxel(4.5 mg/kg)induced peripheral neuralgia in mice after 1 h of 1 d,3 d,4 d,and 7 d.The general state,body weight,threshold of mechanical pain and latency of photothermal pain are observed.Results:After administration of sodium phenylbutyrate in high-dose and medium-dose groups,certain neurotoxicity(temperature drop,drowsiness)is observed,and there is no significant effect on body weight.After drug intervention,the effects of sodium phenylbutyrate on the threshold of mechanical pain reduction(three doses groups)and the latency of photothermal pain reduction(medium and high doses groups)are similar to those of the positive drug pregabalin,which have a good analgesic effect.Three doses of sodium phenylbutyrate(0.5 g/kg,1.0 g/kg and 1.5 g/kg)and positive drugs slightly improve the demyelination of myelinated nerve fibers in mice sciatic nerve induced by paclitaxel.Conclusion:Sodium phenylbutyrate has obvious analgesic effect,and the optimal dose still needs to be further explored.

关 键 词：苯丁酸钠 外周神经痛 紫杉醇 

分 类 号：R965[医药卫生—药理学]