Omega-3多不饱和脂肪酸通过抑制CD147糖基化/MMPs通路改善新生大鼠脑缺血缺氧损伤的机制研究

Neonatal hypoxic/ischemic (H/I) brain injury is a leading cause of morbidity and perinatal mortality. To date, there are limited effective strategies for the prevention and treatment of this condition. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are highly enriched in brain and are known to attenuate H/I-induced brain damage and neurological deficits. Our results also suggest that n-3 PUFA treatment may protect the BBB by inhibiting central and peripheral MMP production and activity. However, its direct signal pathway on neonatal BBB integrity remains pooly understood. CD147 is a type-I transmembrane glycoprotein of the immunoglobulin superfamily (IgSF), known as MMPs inducer and widely expressed on human tumor cells. Study about CD147 on the neonatal ischemic brain injury still lack of evidence. Our previous research gives a clue that decreasing HG/LG-CD147 ratio could be a way to protect the integral of neurovascular unit and promote outcome of ischemic brain injury. Therefore, we hypothesized that n-3 PUFAs mitigate blood-brain barrier disruption by down-regulating highly-glycosylated CD147/MMPs pathway, thus protecting neonatal hypoxic-ischemic brain injury.

新生儿缺血缺氧性脑病是引起围产期婴幼儿急性死亡和永久性神经功能缺陷的常见疾病，尚无有效治疗和预防措施。新生期血脑屏障及缺血损伤后改变对于寻找新生儿缺血缺氧性脑病的有效治疗十分关键。课题前期实验发现，脑缺血缺氧可致Caveolin-1上调，CD147糖基化增加，引起MMPs产生增加导致血脑屏障BBB损害。Omega-3多不饱和脂肪酸（Omega-3 PUFAs）可能通过抑制外周中性粒细胞来源的MMPs的激活减少缺血缺氧早期血脑屏障结构的破坏，最终起到神经保护作用。由此本研究提出假设：Omega-3 PUFAs可能抑制CD147/MMP信号通路，减轻BBB损害从而保护神经元。探讨Omega-3 PUFAs神经保护作用的新机制，旨在为Omega-3 PUFAs作为新生大脑缺血缺氧损伤可能的治疗方案提供部分理论参考。

新生儿缺血缺氧性脑病是引起围产期婴幼儿急性死亡和永久性神经功能缺陷的常见疾病，尚无有效治疗和预防措施。新生期血脑屏障及缺血损伤后改变对于寻找新生儿缺血缺氧性脑病的有效治疗十分关键。课题实验发现，脑缺血缺氧可致Caveolin-1上调，CD147糖基化增加，引起MMPs产生增加导致血脑屏障BBB损害。Omega-3多不饱和脂肪酸（Omega-3 PUFAs）可能通过抑制外周中性粒细胞来源的MMPs的激活减少缺血缺氧早期血脑屏障结构的破坏，最终起到神经保护作用。Omega-3 PUFAs可能抑制CD147/MMP信号通路，减轻BBB损害从而保护神经元。探讨Omega-3 PUFAs神经保护作用的新机制，旨在为Omega-3 PUFAs作为新生大脑缺血缺氧损伤可能的治疗方案提供部分理论参考。