目的:探讨补血生髓方对肿瘤相关性贫血(cancer related anemia,CRA)小鼠的改善作用及可能的作用机制.方法:C57BL/6雌性小鼠腹腔注射苯肼(50mg/kg),并且皮下接种肺癌LLC细胞建立CRA模型,随机分成模型组、EPO组(1365IU/kg)、补血生髓方组(60.67g/kg),每组10只,另取10只正常小鼠作为空白组,给药2周.ELISA检测促红细胞生成素、血清干扰素-γ(interferon-γ,IFN-γ)水平,流式细胞术检测外周血Tregs细胞比例,Real time-PCR及免疫荧光检测缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、程序性死亡-配体1(pro-grammed cell death ligand 1,PD-L1)mRNA及蛋白的表达.结果:与模型组相比,补血生髓方组小鼠的肿瘤体积、肿瘤质量均显著降低(P＜0.01).与空白组相比,模型组血红蛋白、促红细胞生成素、IFN-γ水平显著下调(P＜0.01),外周血Tregs细胞比例显著升高(P＜0.05).与模型组相比,补血生髓方组血红蛋白、促红细胞生成素、IFN-γ水平显著上调(P＜0.01),外周血Tregs细胞比例显著下降(P＜0.01),HIF-1α、PD-L1mRNA和蛋白表达显著降低(P＜0.01).结论:补血生髓方能够改善CRA小鼠的贫血状态,通过下调HIF-1α/PD-L1通路调节CRA小鼠的免疫功能,从而抑制肿瘤的生长.
To explore the improvement effect of Buxue Shengsui Recipe on cancer related anemia mice based on HIF-1 α/PD-L1 pathway
Objective:To explore the improvement effect of Buxue Shengsui Recipe on cancer related anemia(CRA)mice,and to analyze its potential mechanism.Methods:C57BL/6female mice were intraperitoneally injected with phenylhydrazine(50mg/kg)and subcutaneously inoculated with lung cancer LLC cells to establish CRA models.CRA mice were randomly divided into model group,EPO group(1365IU/kg),Buxue Shengsui Recipe group(60.67g/kg).Another 10normal mice were taken as the blank group and administered for 2weeks.Serum levels of erythropoietin and interferon-γ(IFN-γ)were detected by ELISA.The proportion of Tregs cells in peripheral blood was detected by flow cytometry.The expressions of hypoxia inducible factor-1α(HIF-1α)and programmed cell death ligand 1(PD-L1)mRNA and protein were detected by Real time-PCR and immunofluo-rescence.Results:Compared with the model group,volume and weight of tumors in Buxue Shengsui Recipe group were signifi-cantly reduced(P＜0.01).Compared with the blank group,the levels of hemoglobin,erythropoietin and IFN-γ in the model group were significantly down-regulated(P＜0.01),and the proportion of Tregs cells in peripheral blood was significantly in-creased(P＜0.05).Compared with the model group,the levels of hemoglobin,erythropoietin and IFN-γ in Buxue Shengsui Recipe group were significantly up-regulated(P＜0.01),the proportion of Tregs cells in peripheral blood was significantly de-creased(P＜0.01),and the expression of HIF-1α and PD-L1mRNA and protein was significantly decreased(P＜0.01).Con-clusion:Buxue Shengsui Recipe can improve the anemia status and regulate the immune function of CRA mice by down-regula-ting the HIF-1α/PD-L1 pathway,thereby inhibiting tumor growth.
Buxue Shengsui Recipecancer related anemiaimmunityHIF-1αPD-L1
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