糖皮质激素对BXSB狼疮小鼠肾组织fractalkine/CX3CR1表达的影响

Effects of glucocorticoids on the expression of fractalkine and CX3CR1 in kidneys of BXSB mice

目的:研究BXSB狼疮小鼠肾组织趋化因子fractalkine及其受体CX3CR1的表达以及给予泼尼松治疗后的改变,探讨两者在狼疮肾炎发病机制中的可能作用。方法:12周龄雄性BXSB狼疮小鼠随机分成泼尼松治疗组(n=6)和实验对照组(n=6);另取同周龄雄性C57BL/6J小鼠6只作为正常对照组。正常对照组和实验对照组小鼠每天给予0.5mL生理盐水灌胃;泼尼松治疗组小鼠每天给予0.18mg/20gBW的泼尼松溶于0.5mL生理盐水灌胃。持续10周结束实验。应用逆转录-聚合酶链反应(RT-PCR)及Western印迹检测小鼠肾组织frac-talkine和CX3CR1 mRNA和蛋白的表达,并检测小鼠实验室指标以及肾脏组织病理学的变化。结果:BXSB狼疮小鼠肾组织fractalkine以及CX3CR1 mRNA和蛋白表达均较C57BL/6J小鼠明显增高,而经过泼尼松治疗后的BXSB小鼠两者的表达均较未治疗组(实验对照组)明显下降,同时伴有血清免疫球蛋白G(IgG)、IgM、血清抗双链脱氧核糖核酸(dsDNA)抗体水平以及血尿素氮(BUN)、血肌酐(SCr)水平的明显改善,尿蛋白减少;肾小球内免疫复合物沉积和肾脏组织病理学改变亦显著减轻。结论:实验结果提示fractalkine/CX3CR1可能参与了小鼠狼疮肾炎的发病机制,且糖皮质激素可能通过抑制肾脏fractalkine的表达而发挥其治疗效应。

AIM： To observe the expression of chemokine fractalkine, and its receptor, CX3CR1, in kidneys of lupus - prone BXSB mice, and their changes after treatment with prednisone. The role of fractalkine and CX3CR1 in the pathogenesis of lupus nephritis was also discussed. METHODS： Twelve 12 -week- old male BXSB mice were randomly divided into two groups, the prednisone treatment group （ BXSB - prednisone group, n = 6 ） and the experimental control group （BXSB group, n = 6）. Six male C57BL/6J mice at the same weeks of age served as a normal control group （ C57BL/6J group）. Both the C57BL/6J and the BXSB group of mice received a daily intragastric administration of 0.5 mL normal saline. The BXSB - prednisone group of mice was given a daily intragastric administration of prednisone （0. 18 mg/20 g BW） dissolved in 0.5 mL normal saline. All treatments lasted for 10 weeks. The mRNA and protein expressions of fractalkine and CX3CR1 in kidneys of mice were detected by reverse transcription - pelymerase chain reaction （ RT - PCR） and Western blotting analysis respectively. The changes of laboratory index and the kidney histopathology of mice were also investigated. RESULTS： The mRNA and protein expressions of fractalkine and CX3CR1 in kidneys of BXSB mice were significantly higher than those in C57BL/6J mice. The expressions of fractalkine and CX3CR1 in BXSB - prednisone group of mice were much lower than those in BXSB group of mice, accompanied by the lower serum IgG, IgM and anti - dsDNA antibody levels as well as blood urea nitrogen, serum creatinine and urine protein. The glomerular immune complex deposi- tion and the kidney histopathology were also significantly improved in BXSB - prednisone group of mice. CONCLUSION： These results indicate that fractalkine and CX3CR1 participate in the pathogenesis of lupus nephritis in BXSB mice, and the effect of glucocorticoids treatment may be attributed, in part, to its ability to inhibit the expression of fractalkine in kidney.