中文摘要：

目的观察LIMK1mRNA及其蛋白在脆性x综合征（FXS）zb鼠大脑皮层中的表达，探讨其在FXS发病机制中的作用。方法选择雄性FMR1基因敲除型FvB近交系新生鼠和2、4、6周小鼠做为实验组（记为KO^0d、KO^2w、KO^4w和KO^6w，雄性同龄野生小鼠（WT）作为对照组（记为WT^06、WT^2w、WT^4w和WT^6W．每组每时间点9只。取小鼠单侧大脑皮层行LIMK1 mRNA实时荧光定量PCR分析，取另一侧大脑皮层行LIMK1蛋白Westem blotting分析。结果（1）KO^6w组小鼠LIMK1 mRNA含量较同龄组WT小鼠及KO^0d、KO^2w和KO^4w组小鼠明显升高．WT^0d组小鼠LIMK1 mRNA含量明显高于WT^2w、WT^4w和WT^6w组小鼠，差异有统计学意义（P〈0．05）。（2）同龄KO、WT小鼠大脑皮层中LIMK1蛋白含量差异无统计学意义（P〉0．05）；KO^0d组小鼠LIMK1蛋白含量明显低于KO^0d、KO^4w和KO^6w组，WT^0d组小鼠大脑皮层中LIMK1蛋白含量明显低于KO^2w、KO^4w和KO^6w，差异有统计学意义（P〈0．05）。结论LIMK1蛋白的翻译过程在6周时受到明显抑制．反馈性调节转录过程使LIMK1 mRNA表达急剧升高。KO鼠LIMK1蛋白表达下降，从而影响树突棘的骨架蛋白重构，影响树突棘的功能改变，可能是FXS神经系统改变的重要机制之一。

英文摘要：

Objective To observe the mRNA and protein expressions of LIMK1 in the cerebral cortex of mice with FMR1 gene knockout, and explore the roles ofLIMK1 mRNA and LIMK1 protein in the pathogenic mechanism of fragile X syndrome （FXS）. Methods FVB strain male mice with FMR1 gene knockout （KO, n=36, experimental group） and their wild type （WT, n=36, control group） were equally divided into 8 counterpart subgroups （WT^0d, WT^2w WT^4w, WT^6w KO^0d, KO^2w, KO^4w and KO^6W）, respectively, according to different ages. LIMK1 mRNA expression in the left sides of the cerebral cortex were analyzed with RT-qPCR and protein expression of LIMK1 in another side with Western blotting. Results No significant differences of LIMK1 mRNA expression in the cerebral cortex of KO^0d, KO^2w and KO^4w subgroups were noted as compared with that of respective age-matched WT mice （P〉0.05）; but that of KO6w subgroup was significantly increased as compared with that of WT6w subgroup, and KO^0d, KO2w and KO4w subgroups （P〈0.05）; the level of LIMK1 mRNA in WT^d subgroup was obviously higher than that of WT2w, WT4w and WT6w subgroups （P〈0.05）. No statistic differences of L1MK1 protein between the same-age KO and WT mice were noted （P〉0.05）; significantly lower level of LIMK1 protein in KO~d subgroup was found as compared with that ofKO2w KO4w and KO6w subgroups （P〈0.05）; that of WT^0d subgroup was lower than that of WT2w, WT4w and WT6w subgroups （P〈0.05）. Conclusion The translation process of LIMK1 protein is significantly inhibited at 6 weeks and LIMK1 mRNA expression increased sharply based on the feedback adjustment of LIMK1 protein expression declining; once this translation process is inhibited or interrupted, it will affect the dendritic spines skeleton protein reconstruct and lead to the dendritic spines function deficient; the inhabitation of translation process might probably play an important role in the process of dendritic spines maturation and should be an important pathogenic mechanism o