摘要：目的研究巨噬细胞移动抑制因子(MIF)在原发性肾小球肾炎患者肾脏组织中的表达水平及其与巨噬细胞浸润、肾脏病理改变、肾功能损害的相关关系。方法正常人和原发性，肾小球肾炎患者肾组织MIF蛋白、巨噬细胞标记抗原(抗CD68，KP1)的检测应用微波免疫组织化学染色方法检测；MIF的基因表达应用原位杂交方法；MIF与KP1的相关关系应用免疫组织化学双标记技术检测。肾脏组织的病理改变应用常规病理学方法检测。24h尿蛋白、血肌酐的测定按本院检验科常规方法检测。结果正常人肾脏组织仅有少量MIF的表达，原发性肾小球肾炎患者肾脏组织MIF表达水平(包括蛋白和Mrna)显著上调。原发性肾小球肾炎患者肾组织MIF表达水平与KP1+细胞数有显著相关性，MIF表达水平、MIF+KP1+细胞数与肾脏病理改变程度及肾功能损害明显相关。结论MIP在原发性，肾小球肾炎患者肾脏组织的表达水平显著上调，并与肾脏组织巨噬细胞浸润、肾脏病理改变程度、肾功能损害密切相关，提示MIF表达上调可能是原发性肾小球肾炎患者肾损害的重要机制之一。

Expression of macrophage migration inhibitory factor in renal tissne of primary glomerulonephritis and its significance

KONG Yaozhong ,HUANG Yingwei ,CHEN Tongqing,et al.

(Department of Nephrology,the First People＇s Hospital of Foshan,Guangdong Foshan 528000,China)

Abstract：Objective To investigate the expression of macrophage migration inhibitory factor (MIF) in renal tissue of patients with primary glomerulonephritis,and its correlation with renal injury,proteinuria and renal function.Methods MIF protein expression and anti-CD68 (KP1) were detected with a microwave-based double labeling immunostaining method.MIF mRNA expression was detected with digoxin-labelled in situ hybridization method.Results Up-regulated expression of MIF was found in the patients with primary glomerulonephtitis compared to that in the normal renal tissue.MIF positive cells and KP1 positive cells were closely correlated.MIF+ KPI+ cells were strong correlated with renal histological and impaired renal function.Conclusion MIF up-regulates markedly in patients with primary glomerulonephritis,and may play an important role in the mediation of renal damage in human glomerulonephritis.

Keywords：Glomerulonephritis;Macrophage migration inhibitory factor

基金项目：广东省卫生厅科研基金(A1997467)；广东省科委重点攻关项目基金(9827819)

参考文献：

［1］David JR.Delayed hypersensitivity in vitro:its mediation by cell-free substances formed by lymphoid cell-antigen interaction.Proc Natl Acad Sci,1966,56:72-77.

［2］Bernhagen J,Calandra T,Bucala R.Regulation of the immune response by macrophage migration inhibitory,factor:biological and structure features.J Mol Med,1998,76:151-161.

［3］Bernhagen J,Calandra T,Mitchell RA,et al.MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia.Nature,1993,365:756-759.

［4］Bernhagen J,Bacher M,Calandra T,et al.An essential role for macrophage migration inhibitory factor in the tuberculin delayed-type hypersensitivity reaction.J Exp Med,1996,183:277-282.

［5］Lan HY,Mu W,Yang N,et al.De novo renal expression of macrophage migration inhibitory factor during the development of rat crescentic glomerulonephritis.Am J Pathol,1996,149:1119-1127.

［6］Lan HY,Bacher M,Yang N,et al.The pathogenic role macrophage migration inhibitory,factor in immunologically induced kidney disease in the rat.J Exp Med,1997,185:1455-1465.

［7］陈伟英,尹培达,余学清,等.巨噬细胞移动抑制因子在狼疮性肾炎中的作用.中华肾脏病杂志,1998,14:15-19.

［8］Lan HY,Yang N,Metz C,et al.TNF-alpha up-regulates renal MIF expression in rat crescentic glomerulonephritis.Mol Med,1997,3:136-144.

［9］Tesh GH,Nikolic-Paterson DJ,Atkins RC,et al.Rat mesangial cells express macrophage migration inhibitory factor in vitro and in vivo.J Am Soc Nephrol,1998,9:417-427.

［10］Yang N,Nikolic-Paterson DJ.Ng YY,et al.Reversal of established rat cresentic glomerulonephritis by blockade of macrophage migration inhibitory factor(M1F):potential role of MIF in regulating glucocorticoid production.Mol Med,1998,4:413-424.

［11］Lan HY,Yang N,Brown FG,et al.Macrophage migration inhibitory factor in human renal allograft rejection.Transplantation,1998,66:1465-1471.

收稿日期：2000-02-18