基于PI3K /Akt、JAK2/STAT3 双信号通路补阳还五汤促进骨髓干细胞趋化迁移治疗脊髓外伤性截瘫的机制研究

Spinal cord injury with morbidity serious threat to human health.It can not be cured radically now. Mesenchymal stem cells (MSCs) has a multi-directional differentiation potential, can be induced to differentiate into nerve cells, is widely used in spinal cord injury.Applicants previous studies have found that Buyang Huanwu Decoction can promote the transplantation of MSCs migration, is advantageous to the rat spinal cord function recovery.But MSCs migration mechanism in the body is not fully clear.Can Buyang Huanwu Decoction improve the level of IL - 6 or gp130 in the wound area,activate PI3K/Akt, JAK2 / STAT3 signaling pathway.Produce actin and promote MSCs migration?There is no literature reports.This topic to spinal cord injury rat model was established, with behavior, cortical somatosensory evoked potentials to observe spinal cord function, immunohistochemical detection of neurofilament protein and neuron specific enolization enzyme to observe the migration of MSCs differentiation; Western blot method to detect IL - 6, gp130, PI3K/Akt, JAK2 / STAT3 pathway of protein and actin protein expression, discusses the mechanism of Buyang Huanwu Decoction in promoting MSCs migration and the spinal cord functional recovery. This study can provide Chinese and western medicine combined with clinical treatment of spinal cord injury, and to provide theoretical basis and experimental base.

脊髓损伤(SCI)严重威胁人类健康，致残率很高。现无法从根本上治愈。骨髓间质干细胞（MSCs）具有多向分化潜能，可诱导分化为神经细胞，广泛应用于SCI。申请者前期研究发现，补阳还五汤能促进移植的MSCs迁移，有利于大鼠脊髓功能恢复。但MSCs在体内迁移机制尚不清楚。补阳还五汤能否通过提高伤区IL-6或gp130水平，激活PI3K /Akt、JAK2/STAT3 双信号通路，产生肌动蛋白而促进MSCs迁移？目前无文献报道。本课题拟建立SCI大鼠模型，以行为学、皮层体感诱发电位观察脊髓功能，免疫组化检测神经丝蛋白及神经元特异性烯醇化酶观察MSCs迁移分化；Western blot法检测IL-6、gp130、PI3K / Akt、JAK2/STAT3通路蛋白及肌动蛋白的蛋白表达，探讨补阳还五汤促进MSCs迁移和脊髓功能恢复的作用机制。本研究可为中西医结合临床治疗SCI，提供理论依据及实验基础。

1.项目的背景:. 随着现代交通、建筑业的发展，脊髓损伤（spinal cord injury，SCI）的发病率逐年增加。SCI后可造成严重的肢体功能障碍和心理障碍，而有治疗手段的缺乏，不仅严重影响患者的生活质量，使患者丧失劳动能力，并且给家庭和社会造成较大的经济负担，甚至影响社会的安定。传统的治疗主要依靠药物和外科手术，虽然可在一定程度上缓解病症，但疗效有限，无法从根本上解决病患的问题，因此其治疗至今仍然是一个世界性难题。.2.主要研究内容:. (1)研究补阳还五汤联合骨髓间质干细胞移植对脊髓外伤性截瘫的治疗作用； . (2)从PI3K/Akt、JAK2/STAT3双信号通路探讨补阳还五汤促进骨髓间质干细胞趋化迁移治疗脊髓外伤性截瘫的机制。.3.重要结果. 补阳还五汤和MSCs移植改善脊髓损伤大鼠的脊髓损伤，提高了脊髓损伤大鼠的Tarlov评分，倾斜平面临界角度也明显增加，且增加了脊髓组织中Brdu的含量，抑制了模型大鼠中p-JAK2、p-STAT3、p-AKT、GP130、IL-6的蛋白表达水平。.4.关键数据及其科学意义:. 补阳还五汤和MSCs移植能够改善脊髓损伤，且能够抑制p-JAK2、p-STAT3、p-AKT、GP130、IL-6的蛋白；补阳还五汤促进MSCs迁移通过抑制PI3K/Akt信号和JAK2/STAT3信号通路恢复脊髓功能。