Tspan5调控外周肥大细胞向中枢迁移在术后脑损伤中的机制研究

Postoperative brain injury (PBI) is a common complication in aged patients, especially presented with cognitive dysfunction. The underlying explanation for PBI remains to be elucidated in most cases; however, the role of neuroinflammation in the pathogenesis of PBI has gained increasing attention nowadays. Our previous study found that peripheral surgery increased mast cells (MCs) number and induced cognitive dysfunction in BMMCs-Wsh-/- mice, but not in C57BL/6-KITw-sh/w-sh mice. The result suggested that the migration of MCs to brain was related with neuroinflammation and PBI. Interestingly, tetraspanin 5 (Tspan5) was highly expressed in hippocampus after tibial fracture surgery, and the inhibition of Tspan5 decreased the migration of primary MCs. The results of our previous research suggested that Tspan5 regulated the migration of MCs from blood to brain, which might play a role in the pathogenesis of PBI. Based on the previous results, the present study aims to explore the mechanism of how Tspan5 interacts with ADAM-10 to modulate the migration of MCs from blood to brain, thus helping to provide new clues for the prevention, intervention and treatment of patients with PBI.

术后脑损伤（postoperative brain injury，PBI）好发于老年手术患者，而认知功能障碍是其主要表现之一。PBI病因复杂，近年来中枢炎症在PBI发病中的作用备受关注，但具体机制尚不明确。我们前期动物实验发现，脑内肥大细胞缺陷小鼠（BMMCs-Wsh-/-小鼠）胫骨骨折术后海马区肥大细胞聚集，发生PBI，而全身肥大细胞缺陷小鼠（C57BL/6-KITw-sh/w-sh小鼠）认知功能未见异常，提示外周肥大细胞向中枢的迁移可导致PBI。同时，老年小鼠胫骨骨折术后四次跨膜蛋白5（tetraspanin 5，Tspan5）表达上升；且沉默Tspan5可降低肥大细胞的迁移能力，提示Tspan5可能通过促进肥大细胞迁移参与PBI的发生。本项目拟在前期基础上，探讨Tspan5通过结合ADAM-10介导外周肥大细胞向中枢迁移及其对认知功能的作用与机制，为防治PBI提供新思路。

术后脑损伤（postoperative brain injury，PBI）好发于老年手术患者，而认知功能障碍是其主要表现之一。PBI病因复杂，近年来中枢炎症在PBI发病中的作用备受关注，但具体机制尚不明确。我们前期动物实验发现，脑内肥大细胞缺陷小鼠（BMMCs-Wsh-/-小鼠）胫骨骨折术后海马区肥大细胞聚集，发生PBI，而全身肥大细胞缺陷小鼠（C57BL/6-KITw-sh/w-sh小鼠）认知功能未见异常，提示外周肥大细胞向中枢的迁移可导致PBI。同时，老年小鼠胫骨骨折术后四次跨膜蛋白5（tetraspanin 5，Tspan5）表达上升；且沉默Tspan5可降低肥大细胞的迁移能力，提示Tspan5可能通过促进肥大细胞迁移参与PBI的发生。本项目拟在前期基础上，探讨Tspan5通过结合ADAM-10介导外周肥大细胞向中枢迁移及其对认知功能的作用与机制，为防治PBI提供新思路。