【摘要】 目的探讨肿瘤坏死因子诱导蛋白8样因子-2(TIPE2)调控系统性红斑狼疮(SLE)巨噬细胞极化的作用和对实验狼疮小鼠的治疗作用。方法将小鼠分别用活化淋巴细胞来源的DNA(ALD-DNA)诱导狼疮小鼠模型,分为AAV-scr组和AAV-TIPE2组,从小鼠尾静脉注射AAV-TIPE2或AAV-scr病毒溶液。检测极化的巨噬细胞TIPE2mRNA和蛋白表达、小鼠血清抗dsDNA抗体滴度、尿蛋白及肾病理指数。结果(1)转染AAV-TIPE2细胞的TIPE2 mRNA和蛋白表达水平分别是AAV-scr组的(13.5±1.6)倍和(10.8±1.6)倍;(2)AAV-TIPE2组M2巨噬细胞特异分子MGL~+为59.6%,AAV-scr组MGL~+细胞为8.4%;AAV-TIPE2与AAV-scr转染的巨噬细胞M2/M1比值之比为16;(3)重组TIPE2基因的腺病毒相关载体在转染HEK-293中稳定表达,小鼠体内外实验证实AAV-TIPE2能诱导ALD-DNA狼疮小鼠巨噬细胞向M2极化;(4)AAV-TIPE2组血清抗dsDNA抗体、尿蛋白及肾病理等活动指标明显低于AAV-scr组(P<0.01)。结论 TIPE2诱导巨噬细胞极化为M2表型,缓解ALD-DNA诱导狼疮小鼠的病情,可以作为ALD-DNA诱导狼疮小鼠的一种有前景的治疗方法。更多还原

【Abstract】 Objective To investigate the role of tumor necrosis factor(TNF)-alpha-induced protein 8-like 2(TIPE2)for regulating the macrophage polarization in systemic lupus erythematosus and its curative effects on experimental SLE mice.Methods The mice were treated with activated lymphocytes derived DNA(ALD-DNA)for inducing mice model,randomly divided into AAV-scr control group and AAV-TIPE2 experimental group,and injected with AAV-TIPE2 or AAV-scr virus solution from the tail vein of mice.The expression of TIPE2 mRNA and protein in polarized macrophages,serum dsDNA antibody titer,urine protein and renal pathological index were detected.Results(1)The TIPE2 expression level of TIPE2 mRNA and protein in AAV-TIPE2-transfected cells was 13.5±1.6times and 10.8±1.6times of AAV-scr control group respectively.(2)M2 macrophage specific molecule MGL+was 59.6%in AAV-TIPE2 group and MGL+cells in the AAV-scr group was 8.4%.M2/M1 odds ratio of AAVTIPE2 experimental group to AAV-scr control group was 16.(3)The recombinant TIPE2 adenovirus related vector could stably expressed in transfected HEK-293.In vitro and in vivo experiments confirmed that AAV-TIPE2 was able to induce M2 polarization of macrophages in ALD-DNA-induced lupus mice.(4)The serum anti-dsDNA antibody,urinary protein and renal pathology in the AAV-TIPE2 group were significantly lower than those in the AAV-scr group(P<0.01).Conclusion TIPE2 alleviates the disease condition of ALD-DNA induced SLE mice through induction of macrophage polarization to M2 phenotype,which may be used as a promising therapeutic method for ALD-DNA induced SLE mice.更多还原