慢性束缚应激对小鼠海马PD-1/PD-L1表达水平及炎症反应和氧化应激信号通路的影响

Effects of chronic restraint stress on the expression of PD-1/PD-L1 in mouse hippocampus,inflammatory response and oxidative stress signaling pathways

目的观察PD-1/PD-L1在慢性束缚应激(CRS)诱导的焦虑样模型小鼠海马中的表达水平变化以及炎症反应和氧化应激通路相关指标的改变。方法将24只C57BL/6雄性小鼠随机分为正常组和模型组。模型组每日用束缚管束缚应激2 h,连续14 d;正常组不做处理。在CRS期间每隔3 d记录小鼠的体质量变化;通过旷场和高架十字迷宫行为学实验评估两组小鼠的焦虑样行为;行为学结束后,分离出海马组织,利用Western blotting技术检测两组小鼠海马的炎症和氧化应激相关蛋白的表达水平。结果①CRS能诱导小鼠焦虑样行为,并会减轻小鼠的体质量。②与正常组相比较,模型组小鼠海马中的IL-1β和NF-κB表达上调,IL-1Ra表达下调(P<0.01);而PD-1/PD-L1表达水平显著性下降(P<0.01)。③模型组Nrf2、Keap1和HO-1较正常组相比,均显著性下降(P<0.05,P<0.01)。结论CRS可以引起小鼠的焦虑样行为,抑制海马PD-1/PD-L1的表达水平并调节海马炎症和抗氧化通路的表达水平。

Objective To observe the changes in expression level of PD-1/PD-L1 in the hippocampus of anxiety-like model mice induced by chronic restraint stress(CRS)and the changes of related indexes of inflammatory response and oxidative stress pathways.Methods Twenty-four male C57BL/6 mice were randomly divided into normal group and model group.The model group was subjected to restraint stress for 2 h every day for 14 d,while the normal group was not treated.The changes in body mass of mice were recorded every 3 d during CRS.The anxiety-like behaviors of mice were evaluated by open-field test and elevated plus maze test.After the behavioral experiments,hippocampal tissues were isolated,and Western blotting was used to detect the expression levels of proteins related to inflammation and oxidative stress in the hippocampus of mice in the two groups.Results①CRS could induce anxiety-like behaviors and reduce body mass in mice.②Compared with the normal group,the expressions of IL-1βand NF-κB in the hippocampus of mice in the model group were up-regulated and the expression of IL-1Ra was down-regulated(P<0.01),while the expression levels of PD-1/PD-L1 were significantly decreased(P<0.01).③Nrf2,Keap1 and HO-1 in the model group were significantly lower than those in the normal group(P<0.05,P<0.01).Conclusion CRS can induce anxiety-like behaviors in mice,inhibit the expression of PD-1/PD-L1 in hippocampus and regulate the expression of inflammatory and antioxidant pathways in hippocampus.