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目的观察FK506对BXSB狼疮性肾炎小鼠治疗作用,初步探讨其作用机制。方法 6只12周龄雄性C57BL/6小鼠为正常对照组,12只12周龄雄性BXSB小鼠随机分为LN治疗组和LN未治疗组。治疗组予FK506 2 mg/kg隔日腹腔注射,未治疗组、正常对照组予NS 0.2 ml隔日腹腔注射,治疗至20周龄。PASM染色法观察肾组织病理变化,直接免疫荧光法观察肾组织IgG沉积,ELISA法检测血清抗-dsDNA抗体和IL-18水平,RT-PCR法检测肾组织IL-18 mRNA表达水平,免疫组化法检测肾组织IL-18表达水平。结果治疗组小鼠肾脏病理学改变明显好转,肾组织免疫球蛋白沉积减少,血清抗-dsDNA抗体和IL-18水平、肾组织IL-18mRNA和蛋白表达水平均低于未治疗组。结论 FK506对BXSB小鼠肾损害具有良好的治疗作用,抑制IL-18 mRNA的表达可能是FK506治疗LN的作用机制之一。
Objective To observe the therapeutic effect of FK506 on mice with BXSB lupus nephritis and to explore its mechanism. Methods Six male C57BL / 6 mice of 12 weeks old were normal control group and 12 male BXSB mice of 12 weeks old were randomly divided into LN treatment group and LN untreated group. The treatment group was intraperitoneally injected with FK506 2 mg / kg every other day. The untreated group and the normal control group were intraperitoneally injected with NS 0.2 ml every other day for 20 weeks. PASM staining was used to observe the histopathological changes of renal tissues. The deposition of IgG in renal tissues was observed by direct immunofluorescence assay. The levels of anti-dsDNA antibody and IL-18 in serum were measured by ELISA. The expression of IL-18 mRNA in renal tissues was detected by RT- Method to detect the expression of IL-18 in renal tissue. Results The pathological changes of kidney in treatment group were improved obviously, the deposition of immunoglobulin in kidney tissue was decreased, the level of anti-dsDNA antibody and IL-18 in serum and the level of IL-18 mRNA and protein in renal tissue were lower than those in untreated group. Conclusion FK506 has a good therapeutic effect on renal damage in BXSB mice. Inhibition of IL-18 mRNA expression may be one of the mechanisms of FK506 in the treatment of LN.