长期酗酒可通过破坏血脑屏障(BBB)加重缺血性脑损伤，其中周细胞可发挥重要作用。研究发现，周细胞可发挥神经炎症作用，其中TLR4与NLRP3炎症小体通路被广泛研究。但其在酒精加重BBB破坏中的神经炎症作用目前尚不明确。我们前期通过细胞实验发现氧-葡萄糖剥夺/复氧(OGD/R)后周细胞NLRP3通路被激活，而酒精处理后的周细胞可上调TLR4表达，再给予OGD/R处理后，NLRP3通路的激活明显高于单纯OGD/R组。基于以上预实验结果，我们提出假设：慢性酒精摄入可造成脑周细胞TLR4的预激活，在缺血性脑卒中诱导的周细胞非TLR4依赖的NLRP3炎症小体激活的基础上，预激活的TLR4可进一步活化NLRP3炎症小体通路，诱导神经炎症的级联放大，加重BBB的破坏。本研究拟利用动物细胞模型、转染技术等，旨在揭示周细胞对长期饮酒加重缺血性脑损伤中BBB破坏的炎性调控机制，提供潜在的治疗靶点。

Chronic alcoholism can aggravate ischemic brain injury by damaging the blood-brain barrier (BBB), in which pericytes play an important role. Studies have shown that peripheral cells can play a role in neuroinflammation, and the pathways of TLR4 and NLRP3 have been extensively studied. However, its neuroinflammatory role in alcohol aggravating BBB damage is still unclear. In our previous cell experiments, we found that the NLRP3 pathway was activated in peripheral cells after oxygen-glucose deprivation/reoxygenation (OGD/R). While the TLR4 expression was up-regulated in peripheral cells after alcohol treatment. After OGD/R treatment, the activation of NLRP3 pathway was significantly higher than that of the OGD/R group. Based on the above results, we hypothesized that chronic alcohol intake can cause preactivation of TLR4 in periencephalic cells. On the basis of TLR4-independent NLRP3 inflamosome activation in periencephalic cells induced by ischemic stroke, preactivated TLR4 can further activate NLRP3 inflamosome pathway, induce neuroinflammatory cascade amplification, and aggravate BBB destruction. This study intends to use animal cell models and transfection techniques to reveal the inflammatory regulatory mechanism of pericytes for BBB damage in ischemic brain injury caused by long-term alcohol consumption, and to provide potential therapeutic targets.