中国血液净化

›› 2008, Vol. 7 ›› Issue (11): 610-614.

• 基础研究 • 上一篇    下一篇

基质金属蛋白酶在大鼠肾小球硬化中的表达

赵慧颖 黄 雯 黄海长   

  1. 首都医科大学附属北京同仁医院肾内科；北京大学附属第一医院肾脏病研究所
  • 收稿日期:2008-08-07 修回日期:1900-01-01 出版日期:2008-11-12 发布日期:2008-11-12

Expression of matrix metalloproteinases in glomerulosclerosis in rats

ZHAO Hui-ying1, HUANG Wen1, HUANG Hai-chang   

  1. 1Department of Nephrology, Beijing Tongren Hospital, Beijing 100730; 2Division of Nephrology, Peking University First Hospital, Beijing 100034, China
  • Received:2008-08-07 Revised:1900-01-01 Online:2008-11-12 Published:2008-11-12

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摘要： 目的 检测MMP-2和MMP-9在大鼠局灶节段肾小球硬化中的表达，探讨其与细胞外基质沉积的关系。方法 12只雄性Wistar大鼠，实验组7只，一次性静脉注射氨基核苷嘌呤霉素9mg﹒100g-1体重，对照组5只，静脉注射生理盐水一次，动态观察尿蛋白定量变化。第20周末宰杀，腹主动脉取血，检测血浆白蛋白、血脂、肾功能。留取肾脏，制备病理标本。应用免疫组织化学法观察两组大鼠肾组织中MMP-2、MMP-9和FN的表达，分析其在肾组织中的相对含量，及与蛋白尿程度的相关性。结果 FSGS模型组大鼠用药后尿蛋白定量显著增高，血总胆固醇显著增高。肾脏病理变化示部分肾小球局灶节段硬化或全球性硬化，细胞外基质节段性增多。MMP-9在正常大鼠肾小球上皮细胞和内皮细胞有少量表达，在模型组大鼠肾组织中的表达显著减少(P＜0.05)；MMP-9的表达与尿蛋白定量之间无显著相关性。MMP-2在正常大鼠的肾小球动脉和肾小管间质有少量表达，在模型组大鼠肾组织中，MMP-2的表达略有减少(P＞0.05)；MMP-2的表达与尿蛋白的定量之间无显著相关性。在正常大鼠肾组织中FN表达于肾小球系膜区，基底膜及肾间质处，在模型组大鼠肾组织中FN的表达明显增多(P＜0.05)。FN的表达与尿蛋白定量、MMP-2的表达无显著相关性，与MMP-9的表达呈直线负相关。结论 局灶节段肾小球硬化时，MMP-9的表达下调，可以引起FN降解减少，细胞外基质沉积，促进肾小球硬化的发生。

关键词: 基质金属蛋白酶 肾小球硬化

Abstract: Objective To assay the expression change of matrix metalloproteinasea-2 (MMP-2) and matrix metalloproteinasea-9 (MMP-9) in focal segmental glomerulosclerosis in rats, and to investigate the relationship between the expression of MMP-2 and MMP-9 and the accumulation of extracellular matrix (ECM) in the kidney in these rats. Materials and methods We divided 12 Wistar rats into test group and control group. The model of focal segmental glomerursclerosis (n = 7) was made by intravenous injection of puromycin aminonucleoside (PAN) 9mg/100g-1 body weight. Rats in control group (n = 5) were injected with 3ml 0.9% sodium chloride. Proteinuria and serum creatinine, lipids and protein were examined. Twenty weeks after the injection rats were sacrificed and their kidneys were taken for examination. Renal MMP-2, MMP-9 and fibronectin (FN) were examined by Immunohistochemistry. Positive immunohistochemical signals were quantitatively analysed using the Image-pro software. Results Rats in the test group had prominent protienuria and the increase of serum lipids. Pathologically, the kidney showed focal segmental sclerosis or sclerosis of the whole glomerulus in a part of glomeruli. ECM was segmentally accumulated in the kidney. MMP-9 normally expresses in glomerular endothelial and epithelial cells at a low level, but the expression decreased significantly in glomeruli of the rats in test group (P<0.05). There was no significant relationship between the MMP-9 expression and proteinuia. MMP-2 normally expresses in small renal arteries and the interstitium around renal tubules at a low level, but the expression decreased insignificantly in kidney of the rats in test group (P>0.05). FN normally expresses in glomeruli mesangial areas, glomerular basement membrane and renal interstitium, and the expression increased significantly in kidney of the rats in test group (P<0.05). FN expression negatively correlated with MMP-9 expression, but had no relationship with MMP-2 expression and proteinuria. Conclusion In the pathogenesis of focal segmental glomerulosclerosis, MMP-9 expression is down-regulated, resulting in the decrease of FN catabolism and the ECM accumulation.

Key words: Glomerular sclerosis

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