角膜移植排斥（CTR）是角膜移植失败的主要原因，治疗棘手。Mφ是器官移植排斥的主要效应细胞。我们前期研究发现雷公藤红素（Celastrol）通过调节Mφ减轻角膜移植排斥反应，具体机制尚不完全清楚。既往研究显示TLR4/MyD88/NF-κB信号通路在器官移植排斥中发挥重要作用，Mφ高表达TLR4，我们也发现Celastrol抑制MφNF-κB活性。因此我们大胆推测：TLR4/MyD88/NF-κB存在CTR中，Celastrol也许是通过TLR4/MyD88/NF-κB通路调控Mφ实现其抗CTR效应。本课题拟制备负载Celastrol的正离子纳米胶束，以增强Celastrol水溶性及角膜通透性，明确Celastrol在CTR中的作用及其调节Mφ抗CTR机制，有望加深对 CTR发生机理的理解；结合新兴的纳米技术，为Celastrol治疗器官移植排斥以及寻找新的治疗策略提供理论依据。

Corneal transplantation rejection（CTR), the main reason for the failure of allogeneic corneal transplants, is still a therapeutic challenge for ophthalmologists. Macrophages (Mφ), as the main inflammatory cells, play a key role in organ transplant rejection. Our preliminary show that celastrol prolonged rat corneal allograft survival through suppressing the macrophage infiltration. However, the exact mechanism involved in celastrol modulation of CTR remains unclear. Previous studies have suggested that TLR4/MyD88/NF-κB pathway plays a vital role in organ transplant rejection. TLR4 is highly expressed in macrophages. We also find that celastrol inhibits the activity of NF-κB in macrophages. Therefore, we speculate that TLR4/MyD88/NF-κB pathway play a pivotal role in the inhibiting effect of celastrol on macrophages in CTR. In this present study, we would like to develop celastrol-loaded positively charged micelles based on a triblock copolymer to better improve the hydrophilicity of celastrol and enhance the corneal penetration after topical application. And then we will further explore the potential mechanism of celastrol-mediated modulatory effects on macrophages in CTR. It is expected that this study might constitute a deep understanding of the underlying mechanism of CTR. It will be of help in offering new therapeutic options and explore a useful clinical therapeutic strategy for organ transplant rejection.