增强姜黄素调控小胶质细胞极化和保护缺血性脑卒中的机制研究

Microglial toward M1 polarization induced by ischemic stroke can cause inflammatory cascade response and contribute to neuronal apoptosis. Curcumin has become a focus of attention in inhibiting inflammatory damage induced by M1-type polarization. Our previous experiments found that NPCurcumin could overcome the blood-brain barrier and deliver curcumin to microglia in the penumbra, and reduce the volume of this ischemic brain. NPCurcumin could inhibit M1 polarization and protect neuron under oxidative stress, which was closely related to the change of Nrf2 and STAT1 molecules, but its mechanism was still unknown. Therefore, we propose that Nrf2/STAT1 signal is the key mechanism of suppressing M1 polarization by NPCurcumin. In additon, NPCurcumin has the better neuroprotective effects than curcumin. In vitro, we will investigate the mechanism of M1 polarization regulated by Nrf2/STAT1 signal. In vivo, we will analyze whether NPCurcumin can inhibit inflammation and protect dying neurons, and explore its mechanisms, which will provide new methods for treating ischemic stroke.

小胶质细胞（Microglia,MG）向M1型极化引发的炎症级联反应，是缺血性脑卒中神经元凋亡的重要原因。姜黄素能够抑制MG介导的炎症损伤，是神经保护药物的研发热点。我们预实验发现：纳米载体携载姜黄素（NPCurcumin）能克服姜黄素难以透过血脑屏障的缺点，将其递送到半暗带；在氧化应激的条件下，NPCurcumin抑制M1型极化与Nrf2、STAT1分子密切相关。为此，我们提出Nrf2/STAT1信号是NPCurcumin抑制M1型极化的关键机制，NPCurcumin能增强姜黄素的神经保护作用。本项目拟通过上调或下调Nrf2、STAT1的表达，探讨Nrf2/STAT1信号调控NPCurcumin抑制MG向M1型极化的机制；探讨NPCurcumin调控MG极化与保护濒死神经元的机制，为缺血性脑卒中的治疗提供新的方法。

小胶质细胞（Microglia，MG）向M1型极化引发的炎症级联反应，是缺血性脑卒中神经元凋亡的重要原因。姜黄素能够抑制MG介导的炎症损伤，是神经保护药物的研发热点。本项目研究发现：1）纳米载体携载姜黄素（Curcumin loaded with nanoparticle，NPCurcumin）能够通过损伤的血脑屏障，其能将姜黄素递送到半暗带；2）在氧化应激的条件下，NPCurcumin能抑制小胶质细胞向M1型极化；3）Nrf2/STAT1信号是NPCurcumin抑制M1型极化的关键机制；4）NPCurcumin能增强姜黄素的神经保护作用，为缺血性脑卒中的治疗提供新的方法。