纳米雄黄靶向PD-1/PD-L1通路调节MRL/lpr小鼠脾细胞增殖研究

Nano Realgar targeting PD-1/PD-L1 pathway to regulate splenocytes proliferation in MRL/lpr mice

目的:研究纳米雄黄对MRL/lpr鼠脾细胞的影响及是否是通过程序性死亡蛋白1(PD-1)/程序性死亡蛋白配体1(PD-L1)作用于狼疮鼠。方法:将6只BABL/C小鼠用作正常组,将24只MRL/lpr狼疮鼠随机分为模型组,高、中、低剂量治疗组,每组6只。通过管饲法连续给药8周,脱颈法杀死所有小鼠。采用组织病理学切片观察脾脏损伤,Western Blot法检测PD-L1、PD-1蛋白表达,ELISA法检测血清IL-10水平。结果:正常组脾脏组织形态正常,血清IL-10水平正常。纳米雄黄各剂量治疗组PD-L1、PD-1蛋白表达均显著高于正常组及模型组(P<0.01,P<0.05),其脾脏组织形态较模型组明显改善,IL-10水平也显著降低(P<0.05)。结论:纳米雄黄通过PD-1/PD-L1信号通路抑制脾细胞活化,有益于狼疮鼠病情改善。

Objective:To study the effect of nano Realgar on the splenocytes of MRL/lpr mice and whether PD-1/PDLI plays a role among it.Methods:Six BABL/C mice were used as the normal group,and 24 MRL/lpr mice were randomly divided into model group,high-dose treatment group,medium-dose treatment group,low-dose treatment group.All mice were continuously administered by gavage for 8 weeks,and all mice were killed by neck breaking.Histopathological sections were used to observe the damage of the spleen,Western Blot was used to detect the protein expression of PD-L1 and PD-1,and the level of IL-10 was detected by ELISA.Results:In the normal group,the spleen tissue morphology was normal and the IL-10 level was normal.The protein expressions of PD-LI and PD-1 in the nano-realgar groups were higher than those in the normal group and model group(P<0.01,P<0.05).Compared with the model group,the morphology of the spleen in the nano-realgar groups were significantly improved,and the level of IL-10 was also significantly decreased(P<0.05).Conclusion:Nano Realgar inhibits the activation of splenocytes through PD-1/PD-L1 signaling pathways,and it is beneficial to the improvement of lupus mice.