GSK3抑制剂氯化锂对Fmr1基因敲除小鼠的痛觉敏感性的影响  

The therapeutic effect of lithium chloride on algesthesia sensitivity of Fmr1 knockout mouse

作　　者：方敏华[1] 陈希[1] 孙卫文[1] 曹开谊[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,广东广州510260 [2]广州医科大学实验动物中心,广州510182

出　　处：《解剖学研究》2013年第4期249-255,共7页Anatomy Research

基　　金：广东省科技计划项目(2008B030301371)

摘　　要：目的探讨氯化锂对Fmr1基因敲除小鼠(KO鼠)的痛觉敏感性的影响及机制。方法 8周龄KO小鼠第1天测定热刺激缩足反射潜伏期(PWTL)值,作为基础痛阈,第2、3、4、5天连续腹腔注射氯化锂,给药30 min后测定PWTL值,第6天给药30 min后取腰骶膨大段脊髓组织,通过免疫印迹技术检测KO及WT鼠脊髓水平的GSK3β和P-GSK3β的变化。结果8周龄KO鼠的痛阈均比同周龄WT鼠的痛阈高。使用氯化锂后,KO鼠痛阈下降,且与WT鼠相比差异无统计学意义。8周龄KO鼠脊髓腰骶膨大段后角边缘层及胶状质的P-GSK3β的表达较WT鼠明显减少。使用氯化锂后,KO鼠脊髓腰骶膨大段后角边缘层及胶状质的P-GSK3β的表达增多,而WT鼠的变化不明显。8周龄KO鼠及WT鼠脊髓腰骶膨大段后角边缘层及胶状质的GSK3β的表达在用药前后均无明显改变。结论 KO鼠热痛觉阈值增高,热痛觉敏感性降低。KO鼠腰骶膨大段脊髓后角的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后角中的P-GSK3β的表达而改善KO的鼠热痛觉敏感性。Objective To study the therapeutic effect and mechanism of lithium chloride on algesthesia sensitivity as well as glycogen synthase kinase3β （GSK3β） activities of Fmrl knockout mice （KO mice）. Methods Paw withdraw thermal latency （PWTL） of 8-weeks-old KO mouse and their wild type counterparts （WT mouse ） were measured as the basic pain threshold. Lithi- um chloride was injected intraperitoneally with various dosages of for 5 days. 30 minutes after injection, Paw withdraw thermal la- tency （PWTL） was measured for the following 4 days. On day 6, lumbosacral enlargement of spinal cord was prepared and im- munoblotting was used to detect the changes of GSK3β and P-GSK3βon spinal level of both KO and WT mice. Results 8-weeks- old KO mice had higher basic pain threshold than that WT mice. After lithium administration, pain threshold of KO mouse was re- duced to the level of WT mouse. We observed that the expression of P-GSK3β significant decreased in marginal lamina and substan- tia gelatinosa of posterior horn of lumbosacral enlargement in KO mouse. After lithium administration, P-GSK3β expression of KO mouse was reduced to the level of WT mouse in those tissues. However, lithium could not modify GSK3β expressions in marginal lamina and substantia gelatinosa of posterior horn of lumbosacral enlargement in either KO or WT mouse. Conclusion KO mice had higher pain threshold, which indicated that their algesthesia sensitivity were reduced. And it might cause by decreasing P-GSK3β expression in posterior horn of lumbosacral enlargement in KO mice. Moreover, lithium chloride could ameliorate KO mice＇ s algesthesia sensitivity by enhancing P-GSK3β expression in posterior horn of lumhosacral enlargement of them.

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 磷酸化糖原合成酶激酶-3β 氯化锂 

分 类 号：R749.94[医药卫生—神经病学与精神病学]