GSK3抑制剂氯化锂对Fmr1基因敲除小鼠痛觉敏感性的影响  

Effect of lithium chloride on pain sensitivity in Fmr1 knockout mice

作　　者：陈希[1] 曹开谊[1] 孙卫文[1] 陈斐荻 黄越玲[2] 沈岩松[1] 戴丽军[2] 易咏红[1] 陈盛强[1] 

机构地区：[1]广州医科大学第二附属医院,510260 [2]广州医科大学实验动物中心,510182

出　　处：《实用医学杂志》2013年第23期3847-3849,共3页The Journal of Practical Medicine

基　　金：广东省自然科学基金项目(编号:815101700100005);广东省科技计划项目(编号:2009B030801368)

摘　　要：目的:探讨氯化锂对Fmr1基因敲除小鼠(KO鼠)痛觉敏感性的影响及机制。方法:8周龄KO鼠及野生型(WT鼠)小鼠第1天测定热刺激缩足反射潜伏期(paw withdraw thermal latency,PWTL)值作为基础痛阈,第2～5天腹腔注射氯化锂后测定PWTL值,第6天给药后取脊髓腰骶膨大段组织,通过免疫组化及Western blot检测实验小鼠脊髓GSK3β和P-GSK3β水平的变化。结果:KO鼠的PWTL值比WT鼠明显升高。使用氯化锂后,KO鼠PWTL值恢复至WT鼠水平。KO鼠脊髓P-GSK3β表达较WT鼠明显减少。使用氯化锂后,KO鼠脊髓P-GSK3β表达增多。结论:KO鼠热痛觉敏感性降低。KO鼠脊髓P-GSK3β表达减少可能是KO鼠热痛觉敏感性降低的原因之一;氯化锂可能通过增加脊髓中P-GSK3β的表达而改善KO鼠热痛觉敏感性。Objective To explore the effect of lithium ehloride on pain sensitivity in Fmrl knockout mice （KO mice） and the mechanism of action. Methods Paw withdraw thermal latency （PWTL） was measured in 8- week-old KO mice and wild type mice （WT mice） as the basic pain threshold on clay one, and was measured again from day 2 to 5 after lithium injection. On day 6, the spinal cord of the mice was removed after lithium injection. Expressions of glycogen synthase kinase 3[3 （GSK3[3） and P-GSK3[3 in the spinal cord in both KO and WT mice were detected with immunohistochemistry and Western blot. Results KO mice had longer PWTL than WT mice. After lithium administration, PWTL in KO mice was returned to the same level as that in WT mouse. Expression of P-GSK313 significantly decreased in the spinal cord in KO mice; however, it was increased after lithium administration. Condnsions Pain sensitivity declines in Ko mice. An decrease in the expression of P-GSK3[3 in the spinal cord can be one of the causes for the decline in pain sensitivity in KO mice. Lithium chloride may improve pain sensitivity by enhancing the expression of P-GSK3[3 in the spinal cord.

关 键 词：脆性X综合征 FMR1基因敲除小鼠 热刺激缩足反射潜伏期 P-GSK3β 氯化锂 

分 类 号：R965[医药卫生—药理学]