Abstract: Objective  To explore the effects of lipopoly saccharide (LPS) pretreatment on endotoxin-induced uveitis (EIU) and the change of PI3K/AKT pathway. Design Experimental study. Participants Male pathogen-free Wistar rats (8-10 weeks old, weighing 180-200 g). Method Wistar rats were randomly divided into normal control (NC) group, endotoxin tolerance (ET) group and EIU group, with 30 rats in each group. EIU was induced by a subcutaneous injection of 200 μg LPS. For the ET group, induction of EIU was preceded by daily intraperitoneal injection of 0.1 mg/kg LPS for five days. EIU and NC groups were injected with saline of the same volume for 5 consecutive days. On day 6, ET group and EIU group received subcutaneous injection of 200 g LPS at the same time, and NC group received injection of saline. Clinical scores were graded 24 h after EIU under a slit lamp microscope. HE stain was performed to observe the histopathology. Aqueous humor TNF-α concentration was quantified with enzyme-linked immunosorbent assay. The expressions of PI3K and AKT in iris were detected through Western blot analysis. Main Outcome Measures Inflammation score of the animal models, HE stain, aqueous humor TNF-α, PI3K/AKT protein expression. Results Clinical score in ET group, EIU group , NC group was 1.65±0.49, 6.65±0.59, 0.20±0.41, respectively （?字2= 53.261, P=0.001）. The pathological score of in ET group, EIU group, NC group was 0.6±0.5, 3.8±0.4, 0.2±0.4, respectively (?字2= 46.137, P=0.001）. The concentration of TNF-α in aqueous humor of in ET group, EIU group, NC group was 10.58±0.67(pg/ml), 30.96±1.55(pg/ml), 10.32±0.61(pg/ml), respectively (F=260.08, P=0.03).  PI3K of Western blot in ET group, EIU group, NC group was 0.197±0.019, 0.539±0.017, 0.453±0.014, respectively（F=210.66, P=0.002）. AKT of Western blot in ET group, EIU group, NC group was 0.234±0.019, 0.553±0.013, 0.428±0.002, respectively（F=275.35, P=0.001）. Conclusions ET can reduce the inflammatory response of EIU in rats, and down-regulate the expression of PI3K and AKT in iris ciliary body tissue. This protective mechanism of ET against EIU may be associated with PI3K/AKT signaling pathway. (Ophthalmol CHN, 2020, 29: 50-54)

Key words: endotoxin-induced uveitis, endotoxin tolerance, PI3K/AKT