MSCs移植治疗脑损伤等神经性疾病的免疫调节作用已成为目前研究热点，本课题组在前一个NSFC项目的研究中发现，MSCs内源性分泌大量IL-6的同时，对损伤细胞具有抗凋亡的作用，促进H2O2损伤的PC12细胞神经功能的恢复。然而，MSCs移植过程中IL-6在损伤微环境中的具体作用靶点和调节机理目前尚不清楚。本项目拟在前一个研究课题新发现的基础上，以MSCs内源性分泌的IL-6为切入点，通过已成功建立HIBD动物模型、ODG模型和共培养技术，以siTLR2、siIL-6和AdIL-6重组腺病毒为工具，从MSCs分泌IL-6分子机制-MSCs移植治疗HIBD中IL-6的调节作用-MSCs来源的IL-6作用靶点及其信号通路开展研究。通过体外机制研究、体内机制验证、体外作用靶点探索三个不同层面深入研究，旨在揭示MSCs移植治疗HIBD中IL-6的免疫调节机制，为促进细胞治疗神经性疾病提供新的途径。

Immunomodulation of MSCs is more efficient at restoring biological function of injured tissue than on trans-differentiation during transplantation. However, the exact mechanisms and characteristics of MSCs on immunoregulation are still unknown, especially in the damaged niche after hypoxic-ischemic insult. It is a study hotspot on the immunomodulation of MSCs transplantation to treatment brain damage resulting in neural disorders till now. In the last funding of NSFC, we found that MSCs endogenously secreted lots of IL-6 and suppressed apoptosis of the damaged PC12 cells following H2O2 treatment in order to improving neural functions. However, the specific targets and exact mechanism involved in IL-6 regulating damaged microenvironment following MSCs transplantation remain unknown. In our previous studies, we have already built the animal model of hypoxic-ischemic brain damage (HIBD), as well as cell models of oxygen-glucose deprivation (OGD) and coculture. Meanwhile, we have gotten several recombinant adenovirus of siTLR2, Ad-IL-6. On the basis of the front new discoveries from the last project, we will take endogenous IL-6 of MSCs as the keypoint and HIBD as therapy target. The current study will determine the molecular mechanism of IL-6 secretion from MSCs in vitro using associated recombinant adenovirus of siTLR2, Ad-IL-6 and siIL-6 and some agonists, and then test IL-6 immunomodulatory function after MSCs transplantation in vivo through HIBD model, at last find the targets and the key proteins in associated signaling pathway of IL-6 with OGD model and coculture technique. The aim is to reveal the targets and regulatory mechanisms of IL-6 immunomodulatory functions for the treatment of HIBD following MSCs transplantation through the three different levels of the mechanism study in vitro to determinate effects in vivo, and then to discovery the detail targets in vitro. The study can provide reliable experimental basis for cytotherapy nervous diseases and offer a new treatment for improving the clinic therapy of HIBD.