骨髓间充质干细胞移植通过抑制 Notch 信号减轻脊髓损伤。
Transplantation of bone marrow mesenchymal stem cells alleviates spinal cord injury via inhibiting Notch signaling.
机构信息
Department of Pharmacy, Evidence-Based Pharmacy Center, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Aug;23(3 Suppl):31-38. doi: 10.26355/eurrev_201908_18625.
OBJECTIVE
To analyze the mechanism of action by which the bone marrow mesenchymal stem cells (BMMSCs) repair the spinal cord injury (SCI) in rats via the Notch signaling pathway.
MATERIALS AND METHODS
A total of 75 male rats aged about 12 weeks old were equally divided into group A (sham operation group), group B (model group), and group C (model group + BMMSCs). The SCI model was established by Allen's method, and the differences in presenilin-1, Hes1 and Notch proteins among the three groups of rats were evaluated via immunohistochemical staining and Western blotting.
RESULTS
Group B exhibited a lower Basso, Beattie, and Bresnahan (BBB) score at each time point than group A and group C (p<0.05), and the BBB score in group C was lower than that in group A (p<0.05). According to the average optical density analysis results of the immunohistochemically stained proteins, the optical density of presenilin-1 protein in group A was lower than that in both group B and group C (p<0.05), and group C exhibited a lower optical density of presenilin-1 protein than group B. In group A, the protein expression of Hes1 in the bone marrow tissues of rats was not evident and weakly positive. Compared with that in group A, it was substantially raised (p<0.05), and the strongly positively expressed Hes1 proteins were yellow or dark brown in group B. Compared with that in group B, the color of Hes1 proteins was lighter (p<0.05), and the positive level of Hes1 proteins was lowered in group C. Group A showed inconspicuously positively expressed Notch proteins, group B brown active Notch proteins, while group C several brown Notch proteins. The optical density of Notch proteins in group A was overtly lower than that in group B and group C (p<0.05), and it was significantly lower in group C than that in group B (p<0.05). Additionally, group B had an evidently higher expression level of Notch proteins than the other two groups (p<0.05), and the expression level of Notch proteins in group C was a little higher than that in group A (p<0.05).
CONCLUSIONS
BMMSCs inhibit the Notch signals to promote the proliferation and differentiation of rat neurons, thereby repairing spinal neurons.
目的
通过 Notch 信号通路分析骨髓间充质干细胞（BMMSCs）修复大鼠脊髓损伤（SCI）的作用机制。
材料与方法
将 75 只 12 周龄雄性大鼠等分为 A 组（假手术组）、B 组（模型组）和 C 组（模型组+BMMSCs）。采用 Allen 法建立 SCI 模型，通过免疫组化染色和 Western blot 法评估三组大鼠的早老素 1、Hes1 和 Notch 蛋白的差异。
结果
B 组各时间点的 Basso、Beattie、Bresnahan（BBB）评分均低于 A 组和 C 组（p<0.05），C 组的 BBB 评分低于 A 组（p<0.05）。根据免疫组化染色蛋白的平均光密度分析结果，A 组早老素 1 蛋白的光密度低于 B 组和 C 组（p<0.05），C 组的光密度低于 B 组。在 A 组，大鼠骨髓组织中 Hes1 蛋白的表达不明显且弱阳性。与 A 组相比，其表达明显升高（p<0.05），B 组中强阳性表达的 Hes1 蛋白呈黄色或深棕色。与 B 组相比，C 组 Hes1 蛋白颜色较浅（p<0.05），Hes1 蛋白阳性水平降低。A 组 Notch 蛋白表达弱阳性，B 组棕色活性 Notch 蛋白，C 组几个棕色 Notch 蛋白。A 组 Notch 蛋白的光密度明显低于 B 组和 C 组（p<0.05），C 组明显低于 B 组（p<0.05）。此外，B 组 Notch 蛋白的表达水平明显高于其他两组（p<0.05），C 组 Notch 蛋白的表达水平略高于 A 组（p<0.05）。
结论
BMMSCs 抑制 Notch 信号，促进大鼠神经元的增殖和分化，从而修复脊髓神经元。
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