三氧化二砷对BXSB狼疮鼠生存时间及脾细胞分泌白细胞介素-4干扰素-γ的影响

The change of survival length and dynamic secretion of interleukin-4 interferon-gamma induced by arsenic trioxide in lupus-prone BXSB mice

目的探讨三氧化二砷(ATO)对BXSB狼疮小鼠生存时间、外周血抗dsDNA抗体水平及离体脾脏单个核细胞白细胞介素(IL)-4、干扰素(IFN)-γ分泌水平的影响。方法BXSB狼疮小鼠44只,随机分为2组,治疗组予腹腔内注射ATO,对照组注射等量生理盐水,酶联免疫吸附试验(ELISA)测其外周血抗dsDNA抗体水平,并将生存时间作比较:另外,通过体外培养脾脏单个核细胞比较C57和BXSB小鼠脾脏单个核细胞分泌IL-4、IFN-γ水平的差异,然后观察ATO对BXSB小鼠脾脏单个核细胞IL-4、IFN-γ分泌水平的影响,同时观察ATO对细胞活性的影响。结果ATO可延长BXSB狼疮小鼠的生仔时间,显著降低其外周血中抗dsDNA抗体的水平:1μmol/L浓度的ATO对小鼠脾脏单个核细胞的活性无明显影响:与C57小鼠相比,BXSB很疮小鼠脾脏单个核细胞在体外经有丝分裂原刺激之后分泌IL-4、IFN-γ水平较高,ATO能显著抑制其分泌。结论ATO可延长BXSB狼疮鼠的生仔时间,降低其外周血抗dsDNA抗体的水平,提示ATO对BXSB狼疮鼠有一定的治疗作用:ATO抑制该小鼠脾脏单个核细胞IL-4和IFN-γ的分泌可能是其发挥治疗作用的重要机制之一。

Objective To study the effect of arsenic trioxide （ATO） on the expression of anti-dsDNA antibody level and survival time of systemic lupus erythematosus （SLE） prone BXSB mice. The level of interleukin-4 （IL-4）, interferon-gamma （IFN-γ） secreted by spleen mononuclear cell in this SLE model is compared with C57 mice. Besides, the effect of ATO on the secretion of IL-4, IFN-γ is also explored. Methods Forty-four BXSB mice were divided into two groups randomly. One group was treated with ATO by intraperitoneal injection for 3 months, while the other group was given the same vdume of normal saline. Then the concentration of plasmic anti-dsDNA antibody and survival time between ATO treated and untreated mice were compared. By cultivating spleen mononuclear cell in vitro, the effect of ATO on cell activity was detected with cell counter kit-8 （CCK-8）. And the level of IL-4, IFN-γ in the supernatant was measured by enzyme-linked immunoadsordent assay（ELISA）. So the level of IL-4, IFN-γ secreted by spleen mononuclear cells of BXSB and C57 mice could be compared. Furthermore, the level of IL-4, IFN-γ secreted by spleen mononuclear cells from BXSB mice of ATO treated and untreated mice was also compared. Results ATO could significantly decrease the serum anti-dsDNA antibody level in BXSB mice, but their survival time was not extended. The level of IL-4, IFN-γ secreted by spleen mononuclear cells in BXSB mice was higher than C57 mice, ATO could inhibit the secretion. When the concentration of ATO was 1 μmol/L, no effect on the activity of the cultivated cells could be observed. Conclusion The high level of IL-4, IFN-γ plays an important role in the progress of SLE. ATO may be another effective immunosuppressive agent in treating SLE. Suppression the secretion of IL-4, IFN-γ/may be one of its important mechanisms.