MFGE8介导整合素αvβ3-STAT3信号轴调控小胶质细胞极化平衡在创伤性脑损伤中的作用及机制研究

创伤性脑损伤（TBI）后神经炎性反应是导致不良预后的重要因素，小胶质细胞极化平衡在TBI后炎性反应调控中起关键作用，但具体机制尚不清楚。我们前期研究发现TBI后损伤皮层周围小胶质细胞中乳脂肪球表皮生长因子-VIII（MFGE8）表达增加，且靶向结合小胶质细胞表面膜受体整合素αvβ3；MFGE8过度表达可降低促炎型M1小胶质细胞比例，下调STAT3磷酸化水平，减轻TBI后神经炎性损伤。据此，我们推测MFGE8可能通过激活整合素αvβ3-STAT3信号轴促使小胶质细胞向M2型极化，从而缓解TBI后神经炎性反应。本课题拟在体内、外TBI模型中，利用小干扰RNA转染双向调控MFGE8，结合分子生物学和靶向干预技术，阐明MFGE8对TBI后小胶质细胞极化平衡的作用及其潜在调控机制，有助于为TBI早期临床干预提供新的治疗靶点，并奠定理论基础。

Neuro-inflammation damage is an important factor leading to poor prognosis after traumatic brain injury (TBI), and microglial polarization balance plays a key role in the regulation of inflammatory response after TBI, however the specific mechanism remains elusive. Our previous study found that the expression of milk fat globules epidermal growth factor-VIII (MFGE8) in microglia around the injured cortical lesion was increased after TBI, and targeted binding to the integrin αvβ3 receptor located on microglial surface; MFGE8 overexpression could reduce the proportion of pro-inflammatory M1 microglia, down-regulate the level of STAT3 phosphorylation, and reduce inflammation injury after TBI. Accordingly, we hypothesize that MFGE8 may alleviate the inflammation response after TBI by prompting microglial polarization to the M2 type through activation of the integrin αvβ3-STAT3 signaling axis. This study intends to elucidate the effect of MFGE8 on microglial polarization balance after TBI and its potential regulatory mechanism in vivo and in vitro TBI models using siRNA transfection to bidirectionally regulate MFGE8, combined with molecular biology and targeted intervention techniques, which helps to provide new therapeutic targets for early clinical intervention of TBI and lay a theoretical foundation.