参芪麝蓉丸抑制TLR4/MyD88/NF-κB促进巨噬细胞/小胶质细胞由M1向M2表型极化治疗脊髓型颈椎病的机制研究

The spinal cord neural inflammatory response has repair and defense effect in the early stage of cervical spondylotic myelopathy (CSM), while secondary injury in the later stage. In the neural inflammatory response, macrophages/microglia can be polarized to promote inflammatory (M1 phenotype) or anti-inflammatory (M2 phenotype) state, showing the different roles of injury, defense and repair. The TLR4/MyD88/NF-κB signal is the key process of the polarization to M1 phenotype, inhibiting the activation of this pathway and promoting M2 polarization that would plays an important role in the recovery of CSM. The Shenqi Sherong Pill could effectively inhibit the chronic spinal cord inflammation, alleviate the apoptosis of neurons and oligodendrocytes, and promote the recovery of spinal function. This project intends to use network hydrogel compressed CSM rat model, assess the spinal cord function, and test the IL-1β、IL-4、TLR4、MyD88、NF-κB、iNOS and Arg1, aim at the TLR4/MyD88/NF-κB signaling pathway regulating the spinal nerve inflammation, and in-depth study of the mechanism for Shenqi Sherong Pill and its effective components promoting the microglia/macrophages polarization from M1 to M2 phenotype, thereby restoring the spinal function of the CSM.

慢性神经炎症反应在脊髓型颈椎病（CSM）脊髓损伤早期有修复作用，而在后期产生继发性损伤。神经炎症反应中，巨噬细胞/小胶质细胞可极化为促炎（M1表型）或抗炎（M2表型）的状态，表现出损伤或修复作用。TLR4/MyD88/NF-κB信号是巨噬细胞/小胶质细胞向M1表型极化的关键环节，抑制该信号通路，促进巨噬细胞/小胶质细胞向M2表型极化，有助于改善CSM脊髓功能。参芪麝蓉丸能有效抑制脊髓慢性神经炎症反应，减少神经元和少突胶质细胞的凋亡，促进脊髓功能的恢复。本项目拟用聚乙烯醇-聚丙烯酰胺互穿网络水凝胶制备CSM大鼠模型，观察大鼠行为学功能，并检测IL-1β、IL-4、TLR4、MyD88、NF-κB、iNOS和Arg1，从TLR4/MyD88/NF-κB信号通路调节脊髓神经炎症反应角度，深入研究参芪麝蓉丸及其有效组分促进巨噬细胞/小胶质细胞由M1向M2表型极化，从而改善CSM脊髓功能的机制。

慢性神经炎症反应在脊髓型颈椎病（CSM）脊髓损伤早期有修复作用，而在后期产生继发性损伤。神经炎症反应中，巨噬细胞/小胶质细胞可极化为促炎（M1表型）或抗炎（M2表型）的状态，表现出损伤或修复作用。采用参芪麝蓉丸及其有效成分麝香酮和松果菊苷干预造模成功的CSM大鼠，明确参芪麝蓉丸及其有效组分麝香酮和松果菊苷在抑制巨噬细胞/小胶质细胞TLR4/MyD88/NF-κB信号通路改善CSM的脊髓功能的作用。分离和纯化SD大鼠小胶质细胞，或BV2细胞并给予LPS诱导，通过参芪麝蓉丸及其有效成分麝香酮和松果菊苷干预后，从细胞学角度明确参芪麝蓉丸及其有效组分对巨噬细胞/小胶质细胞的促进或抑制作用，明确参芪麝蓉丸及其有效成分通过抑制TLR4/MyD88/NF-κB信号通路促进巨噬细胞/小胶质细胞由M1向M2极化，并一定程度上逆转了NF-κB p65核倾向分布。研究证明参芪麝蓉丸及其有效组分麝香酮和松果菊苷对CSM的脊髓功能的改善作用，为中医药治疗脊髓型颈椎病更准确地立法组方，选择用药，提高疗效提供科学依据。