BXSB小鼠肾组织中MCP-1的异常表达及甲泼尼龙的干预作用

Abnormal expression of monocyte chemoattractant protein-1 in kidneys of BXSB mice and effects of methylprednisolone on it

目的:探讨BXSB狼疮鼠肾组织单核细胞趋化因子1(MCP1)的表达情况及甲泼尼龙(MPS)是否可通过抑制MCP1的表达而缓解狼疮肾炎(LN)。方法:将18周龄雄性BXSB自发性狼疮小鼠随机分成BXSB治疗组(n=6)和对照组(n=6);另随机抽取同龄雄性BALBc小鼠6只为正常对照组。MPS组小鼠每日腹腔注射MPS25mg·kg-1;BXSB小鼠对照组及BALBc小鼠按体质量每日同一时间腹腔注射等体积生理盐水,连续3周。用逆转录聚合酶链反应(RTPCR)研究BXSB小鼠肾脏MCP1mRNA的表达,并观察小鼠24h尿蛋白排泄量。结果:BXSB治疗组与对照组小鼠肾组织均检测到MCP1mRNA的表达,而BALBc正常对照组小鼠未见表达;BXSB治疗组小鼠肾组织MCP1mRNA表达量显著低于对照组(P<0.01);BXSB治疗组24h尿蛋白排泄量显著低于对照组(P<0.01)。结论:MCP1可能参与介导LN的发生、发展;MPS可能通过抑制肾组织MCP1的表达而减轻蛋白尿,从而缓解LN。

Objective To investigate whether monocyte chemoattractant protein-1(MCP 1) mediates lupus nephritis(LN) in BXSB mice and whether methylprednisolone (MPS) ameliorates LN by inhibiting MCP 1 expression. Methods 18-week-old male BXSB mice (n=6) displaying clinical symptoms of glomerulonephritis were treated(i.p.) for 3 weeks with MPS (25 mg·kg -1·d -1) dissolved in NS. BXSB controls were age- and sex-matched BXSB mice (n=6) receiving NS alone. Age- and sex- matched BALB/c mice (n=6) were used as normal controls that were treated in the same way as the BXSB controls. MCP 1 expression was investigated by means of RT PCR. Proteinuria was also evaluated. Results MCP 1 was strongly expressed in kidneys of all BXSB mice, while no signals of expression were found in kidneys of BALB/c mice. MCP 1 expression in kidneys of mice in MPS group dramatically reduced in comparison with that of BXSB control mice( P<0.01). Compared with BXSB control mice, 24 h total amount of urinary protein of mice in MPS groups significantly decreased after three weeks' treatment( P<0.01). Conclusion MCP 1 may mediate LN in BXSB mice. MPS can reduce urinary protein and ameliorate LN of BXSB mice, partly via inhibiting MCP 1 expression in kidney.