Sall2和p21与肌萎缩侧索硬化症海马区病变关系分析

Research on the relationship between SALL2,p21 and hippocampal lesions in amyotrophic lateral sclerosis

目的检测SOD1-G93A突变型肌萎缩侧索硬化症(ALS)转基因小鼠海马中婆罗双树样基因-2(Sall2)和细胞周期抑制因子p21的表达变化及其与ALS海马区病变的关系。方法将33对SOD1-G93A突变型ALS转基因小鼠和同窝野生型(WT)小鼠于95d、108d和122d分别取材,应用RT-PCR、Western blot和免疫组织化学染色实验检测Sall2和p21不同发病时期海马中mRNA和蛋白水平表达变化及其在海马中的表达规律。结果与同窝WT小鼠相比,Sall2 mRNA和蛋白在ALS转基因小鼠海马中108d、122d表达均下调,p21 mRNA水平无明显变化,p21蛋白在108d、122d表达均上调(P<0.05)。免疫组织化学染色结果显示,与同窝WT小鼠相比,122d龄ALS转基因小鼠海马中Sall2免疫反应性降低,而p21免疫反应性升高。结论ALS转基因小鼠中Sall2和p21的表达异常与ALS海马区病变密切相关。

Objective To detect changes in the expression of Spalt-like Gene-2(Sall2)and cell cycle inhibitor p21 in the hippocampus of SOD1-G93 A amyotrophic lateral sclerosis(ALS)transgenic mice and explore the relationship between Sall2 and p21 and the hippocampal lesions of ALS.Methods Thirty-three pairs of SOD1-G93 A mutant ALS transgenic mice and wild-type(WT)mice littermate were sacrificed at 95 d,108 d and 122 d after birth respectively.RT-PCR,Western blot and immunohistochemical staining technique were used to detect the expression of Sall2 and p21 mRNA and protein levels in the hippocampus and their expression characteristics.Results Compared with WT mice littermate,the expression levels of Sall2 mRNA and protein in the hippocampus of ALS transgenic mice were down-regulated on both 108 d and 122 d,while there was no significant change in p21 mRNA level.The expression of p21 protein was up-regulated on both 108 d and 122 d.Immunohistochemical staining showed that the immunoreactivity of Sall2 was decreased in the hippocampus of 122-day-old ALS transgenic mice while the immunoreactivity of p21 was increased,compared with WT mice littermate.Conclusion Sall2 and p21 were abnormally expressed in the hippocampus of ALS transgenic mice,which was closely related to the hippocampal lesions of ALS.