| 齐银矿,文岚,余建萍,李堃毅,刘勇.JAK2/p-JAK2在ALS-SOD1-G93A转基因小鼠发病及进展中的表达.[J].中南医学科学杂志.,2025,(2):221-225. |
| JAK2/p-JAK2在ALS-SOD1-G93A转基因小鼠发病及进展中的表达 |
| Expression of JAK2/p-JAK2 in the pathogenesis and progression of ALS-SOD1-G93A mice |
| 投稿时间：2024-05-14 修订日期：2024-08-20 |
| DOI：10.15972/j.cnki.43-1509/r.2025.02.007 |
| 中文关键词: ALS JAK2 p-JAK2 SOD1 神经变性疾病 ALS-SOD1-G93A转基因小鼠 [ |
| 英文关键词:ALS JAK2 P-JAK2 neurodegenerative disease ALS-SOD1-G93A mouse |
| 基金项目:四川省医学科研青年创新课题计划(Q20047) |
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| 中文摘要: |
| 目的观察酪氨酸激酶2(JAK2)/磷酸化JAK2(p-JAK2)在肌萎缩侧索硬化(ALS)-超氧化物歧化酶1(SOD1)-G93A转基因小鼠发病及进展中的作用。 方法构建带有人类SOD1突变基因的ALS-SOD1-G93A转基因小鼠。用运动缺陷评分系统评价小鼠运动功能,观察小鼠行为学,然后随机取30、60、90天日龄、ALS发病期(onset)、终末期ALS-SOD1-G93A转基因小鼠及130天日龄非转基因小鼠(non-Tg)各6只,分别为30天组、60天组、90天组、onset组、终末期组及non-Tg组。取各组小鼠脊髓腰膨大部,利用Western blotting和免疫组织化学实验观察JAK2、p-JAK2蛋白表达水平。 结果JAK2在ALS-SOD1-G93A转基因小鼠各时期和non-Tg小鼠脊髓腰膨大部中阳性表达均较弱,其中,30天组、60天组、90天组可见具有细胞形态的弱阳性表达,onset组、终末期组表达略增多；non-Tg组、30天组、60天组、90天组p-JAK2阳性表达较弱,主要集中在脊髓前角灰质的运动神经元胞质,但30天组、60天组、90天组偶见呈p-JAK2强阳性表达的胶质细胞,并累及白质,随小鼠日龄增加呈p-JAK2强阳性表达的胶质细胞数量增多,onset组、终末期组p-JAK2阳性表达于胶质细胞且明显增强,广泛累及腰髓灰质和白质。Western blotting结果显示,终末期组JAK2、p-JAK2蛋白表达水平较non-Tg组、30天组、60天组明显增高(P＜0.05)。 结论在ALS-SOD1-G93A转基因小鼠发病过程中,JAK2、p-JAK2表达显著上调,p-JAK2主要表达在发病后ALS-SOD1-G93A转基因小鼠增生的胶质细胞,提示JAK2/p-JAK2在ALS发病机制中具有重要作用。 |
| 英文摘要: |
| AimTo observe the role of Janus kinase (JAK2)/phosphorylated JAK2 (p-JAK2) in the pathogenesis and progression of amyotrophic lateral sclerosis (ALS) in superoxide dismutase 1 (SOD1) G93A transgenic mice. MethodsALS-SOD1-G93A transgenic mice carrying the human SOD1 mutation gene were generated. Motor function was assessed using a motor deficit scoring system, and behavioral observations were conducted. Subsequently, six mice each at 30,60, and 90 days of age, at the onset stage of ALS, at the end-stage of ALS of SOD1-G93A transgenic mice, and 130-day-old non-transgenic (non-Tg) mice were randomly selected and assigned to the 30-day, 60-day, 90-day, onset, end-stage, and non-Tg groups, respectively. The lumbar spinal cord enlargement region was harvested from each group. Western blotting and immunohistochemical assays were performed to evaluate the expression levels of JAK2 and p-JAK2 proteins. ResultsImmunohistochemical results showed that the positive expression of JAK2 was weak in the spinal cord and lumbar enlargement of ALS-SOD1-G93A transgenic mice at different stages and non-Tg mice. Weak positive expression with cellular morphology was observed in the 30-d group, the 60-d group and the 90-d group, while the expression was slightly increased in the onset group and the end-stage group. p-JAK2 positive expression was weaker in the non-Tg group, the 30-d group, the 60-d group and the 90-d group, which mainly concentrated in the cytoplasm of motor neurons in the gray matter of anterior spinal cord horn. However, there were few glial cells with strong p-JAK2 expression in the 30-d group, the 60-d group and the 90-d group, which affected the white matter. As age of the mice increased, glial cells with strong p-JAK2 positive expression increased. In the onset group and the end stage group, p-JAK2 positive expression was significantly enhanced and concentrated in proliferating glial cells. It affected gray and white matter areas of the lumbar spinal cord extensively. Western blotting results showed that the expression levels of JAK2 and p-JAK2 in the end-stage group were significantly higher than those in the non-Tg group, 30-d group, 60-d group groups (P＜0.05). ConclusionIn the pathogenesis of ALS-SOD1-G93A transgenic mice, the expression of JAK2 and p-JAK2 is significantly upregulated. After onset of disease, p-JAK2 is mainly expressed in proliferating glial cells of ALS-SOD1-G93A transgenic mice, indicating that JAK2/p-JAK2 plays an important role in the pathogenesis of ALS. |
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