P53和Parkin共同调节线粒体自噬对BMSCs修复早期ONFH的作用及机制

骨髓间充质干细胞（BMSCs）在股骨头坏死（ONFH）区的存活和干性是决定移植疗效的关键。但是，骨坏死区氧化应激导致移植的BMSCs应激性凋亡和衰老。如何提高BMSCs的存活和干性是尚待解决的难题。研究揭示受损线粒体积累是BMSCs应激性凋亡和衰老的重要原因。我们在BMSCs中上调Parkin并下调P53，可增强线粒体自噬，抵抗BMSCs应激性凋亡和衰老。据此我们推测：P53和Parkin可通过PINKl-Parkin途径调节线粒体自噬，进而抵抗BMSCs应激性凋亡和衰老，提高BMSCs移植疗效。本项目拟采用基因转染等技术，研究P53和Parkin是否通过上述途径调节线粒体自噬，进而干预BMSCs应激性凋亡和衰老；并将P53和Parkin基因转染BMSCs修复早期激素性ONFH模型，利用Micro-CT和免疫学等技术，评估修复效果；为抵抗BMSCs应激性凋亡和衰老、提高移植疗效探求新思路。

The survival and stemness of bone marrow mesenchymal stem cells (BMSCs) in the area of osteonecrosis of the femoral head (ONFH) are the keys to determine the efficacy of transplantation. However, oxidative stress in the osteonecrosis area lead to stress-induced apoptosis and senescence of transplanted BMSCs. It remains to be determined how to improve the survival and stemness of BMSCs. Studies have indicated that the main and important reason for the stress-induced apoptosis and senescence of transplanted BMSCs was the accumulation of damaged mitochondria in cells. Our previous study indicated that the upregulation of parkin and downregulation of P53 in BMSCs can enhance the mitophagy, and resist the stress-induced apoptosis and senescence of BMSCs. Based on these, our hypothesis is that P53 and parkin could regulate mitophagy through the PINKl-parkin pathway, resist the stress-induced apoptosis and senescence of BMSCs, and improve the efficacy of BMSCs transplantation. In the study, gene transfection and other techniques were used to determine whether P53 and parkin could regulate mitophagy through the above pathway, and then intervene the stress-induced apoptosis and senescence of BMSCs. The P53 and parkin genes were transfected into BMSCs to repair early steroid-induced ONFH models, then the repaired effect was evaluated by Micro-CT and immunology. In order to explore new ideas for resisting the stress-induced apoptosis and senescence of BMSCs and improving the effect of transplantation.