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作 者:梁鸣[1] 阳晓[2] 顾海峪[1] 李幼姬[2] 孔庆喻[2] 叶任高[2] 许韩师[2] 余学清[2]
机构地区:[1]广州市第一人民医院,广州510180 [2]中山大学附属第一医院肾脏科,广州510080
出 处:《现代免疫学》2004年第1期36-40,共5页Current Immunology
基 金:国家自然科学基金资助项目 ( 3 0 2 71668; 3 0 0 70 717);高等学校博士学科点专项科研基金资助项目 ( 2 0 0 2 0 5 5 80 5 )
摘 要:为检测狼疮样肾炎小鼠脾、肾组织中钙调磷酸酶 (CaN )活性 ,以探讨其与肾炎小鼠肾组织RANTES表达及肾组织病理改变的关系。采用慢性移植物抗宿主小鼠 (GVHD )狼疮样肾炎模型 ,CaN活性检测采用发色底物法。结果 :(1) 12周模型组肾小球硬化指数及小管间质损伤总积分显著高于 8周模型组 (P <0 0 1) ;(2 ) 12周模型组RANTES蛋白及mRNA表达显著高于 8周模型组 (P <0 0 1) ,FK5 0 6显著抑制狼疮样肾炎小鼠肾组织RANTES蛋白及mRNA表达 ;(3)模型组脾、肾组织中CaN活性显著增强 ,与正常对照组脾、肾组织CaN活性有显著差异 (P <0 0 1) ,FK5 0 6组中CaN活性显著下降 (P <0 0 5 ) ;(4 )狼疮样肾炎小鼠脾组织中CaN活性与血清抗dsDNA抗体水平呈正相关关系 (r1=0 92 5 ,P <0 0 1) ;(5 )狼疮样肾炎小鼠肾组织中CaN活性与肾小球硬化指数及小管间质损伤总积分呈正相关关系 (r2 =0 6 2 6 ,P <0 0 1;r3 =0 772 ,P <0 0 5 ) ,与RANTES蛋白阳性小管数呈正相关关系 (r4=0 6 2 5 ,P <0 0 5 ) ,狼疮样肾炎小鼠肾组织中CaN活性与RANTESmRNA表达呈正相关关系 (r5=0 714 ,P <0 0 5 )。表明狼疮样肾炎小鼠脾细胞存在CaN异常活化 。To study the significance of determination of calcineurin (CaN) activation and its role in the pathogenesis of lupus nephritis,the murine lupoid nephritis model of chronic graft vs host disease (GVHD) was employed,and animals were killed in 8 and 12 weeks period. The CaN activation activity in extracts from spleen and kidney tissues was determined by Biomol green phosphatase test. It was found that the glomerular sclerosis index (GSI) and tubulointerstial injury score were significantly increased in 12 weeks model group and the expression of RANTES and mRNA were significantly higher in this group of mice in comparison with those of the 8 weeks group of mice. FK506 could inhibit the expression of RANTES in lupus model significantly. A specific increase in CaN activity was observed and was distinctly higher in spleen and kidney in comparison with those of controls. FK506 also inhibited the CaN activation in spleen and kidney in lupus significantly. There was a marked correlation between CaN activity in model spleen and the serum anti-dsDNA antibodies. Also,there was a marked correlation between the CaN activity in model kidney and the expression of RANTES mRNA. These results indicate that activation of CaN may play a role in lymphocyte activation and the abnormalities of its activation may participate the renal injuries of lupus nephritis.
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