肿瘤治疗后，体内大量细胞凋亡残骸（凋亡小体）若不及时清除，毒性、炎性物质外泄将引起内环境紊乱、基因突变等，导致肿瘤复发。调控肿瘤细胞凋亡小体吞噬清除的药物及机制尚不明确。我们前期研究发现冬凌草甲素可促进人巨噬细胞吞噬白血病U937细胞凋亡小体，并通过激活PI3K、Ras、炎症通路诱导自噬协同吞噬，然而其调控吞噬的启动性靶点和关键性通路有待更深入揭示。本研究通过体外培养人和小鼠巨噬细胞与白血病细胞凋亡小体共同孵育，及体内腹腔巨噬细胞、外周血巨噬细胞吞噬白血病细胞凋亡小体等模型，采用荧光染色、流式细胞术、siRNA、质粒转染等技术，考察冬凌草甲素促进吞噬作用中，Toll样受体4（TLR4）及其可能激活的NLRP3炎症小体的调控作用，并探索此通路与自噬的相互作用，阐明自噬协同吞噬机制。揭示冬凌草甲素促吞噬作用及关键靶点，将为肿瘤凋亡小体的吞噬清除、防止复发、改善微环境、免疫调节等治疗提供依据。

Induced apoptosis of tumor cells is the main way for tumor therapy, however, if the large number of apoptotic corpse (apoptotic bodies) not be engulfed and removed rapidly, toxic and inflammatory contents will be released to cause internal-environment disturbance, gene mutation, inflammatory injury and immune deficiency disorder, which may further lead to tumor recurrence. The medicine which targeting endocytosis and clearance of tumor apoptotic bodies as well as the mechanism are rarely reported and remains unclear. In our previous study, we found that oridonin could enhance endocytosis of U937 leukemia cells apoptotic bodies by phagocyte through PI3K, Ras, inflammation and autophagy pathways. Nevertheless, the starting targets and key pathways are required to further investigate. In this study, human and murine macrophages will be incubated with UV-induced apoptotic bodies of leukemia cells in vitro, and the regulatory mechanism of Toll-like receptor 4（TLR4）-NLRP3 inflammasome-autophagy pathway in oridonin enhanced endocytosis of apoptotic bodies will be investigated by fluorescent staining, flow cytometry, siRNA and plasmid transfection. The relationship and interaction between TLR4-NLRP3 and autophagy will be revealed. The hypothesis will also be verified in vivo through detecting the endocytosis function of murine peritoneal and peripheral blood macrophage and some immune indices. The original results of promoted effect of oridonin on endocytosis of leukemia apoptotic cells as well as its targets and mechanism will provide the new ideas for leukemia or other tumor adjuvant therapy. It may assist in prevent recurrence, immune regulation and improve the tumor microenvironment.