【摘要】 目的 探讨维生素D3(vitamin D3，VD3)介导肿瘤坏死因子α诱导蛋白8样分子2(tumor necrosis factor-alpha induced protein 8-like 2，TIPE2)对慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)中巨噬细胞功能和表型的调控作用。方法 收集CRSwNP患者(100例)和单纯鼻中隔偏曲患者(100例)的外周血标本，RT-qPCR和Western blot检测TIPE2和精氨酸酶1(Arginase-1，Arg-1)的表达，化学发光法测VD3浓度。在体外巨噬细胞系J774A.1中沉默TIPE2，另在CRSwNP模型小鼠体内过表达TIPE2，并通过过表达TIPE2联合VD3治疗小鼠。Western blot检测TIPE2和Arg-1表达，ELISA检测IL-4和IL-13表达。结果 CRSwNP组中VD3分级降低，TIPE2和Arg-1水平上调(P均<0.05)。Arg-1和TIPE2正相关(r~2=0.994，P<0.05)，二者均与VD3分级负相关(r~2=0.652，P<0.05；r~2=0.745，P<0.05)。J774A.1中沉默TIPE2致Arg-1、IL-4、IL-13下调(P均<0.05)。CRSwNP小鼠体内过表达TIPE2致VD3下调，Arg-1、IL-4、IL-13上调，VD3治疗逆转上述指标(P均<0.05)。结论 VD3通过下调TIPE2的表达抑制CRSwNP中Arg-1、IL-4、IL-13的表达。更多还原

【Abstract】 OBJECTIVE To investigate the regulatory effect of vitamin D3(VD3)-mediated TIPE2 on macrophage function and phenotype in chronic rhinosinusitis with nasal polyps(CRSwNP).METHODS Peripheral blood samples were collected from 100 CRSwNP patients and 100 patients with simple nasal septum deviation.RT-qPCR and Western blot were used to measure the expression of TIPE2 and Arg-1,and chemiluminescence was used to measure VD3 concentration.In the J774A.1 macrophage cell line,TIPE2 was silenced,and in CRSwNP model mice,TIPE2 was overexpressed,followed by treatment with overexpressed TIPE2 combined with VD3.Western blot was used to measure the expression of TIPE2 and Arg-1,and ELISA was used to measure the expression of IL-4 and IL-13.RESULTS In the CRSwNP group,VD3 levels decreased,while TIPE2 and Arg-1 levels increased(all P<0.05).Arg-1 and TIPE2 were positively correlated(r~2=0.994,P<0.05),and both were negatively correlated with VD3 levels(r~2=0.652,P<0.05;r~2=0.745,P<0.05).Silencing TIPE2 in J774A.1 cells led to a decrease in Arg-1,IL-4,and IL-13 levels(all P<0.05).In CRSwNP mice,overexpression of TIPE2 resulted in decreased VD3 and increased Arg-1,IL-4,and IL-13 levels,which were reversed by VD3 treatment(all P<0.05).CONCLUSION VD3 inhibits the expression of Arg-1,IL-4,and IL-13 in CRSwNP by downregulating TIPE2 expression.更多还原