Zou He-qun, Yao Juan, Wang Yu-xin, Wang Jun, Li Duo, Wang Pei
Department of Nephrology, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
Zhonghua Yi Xue Za Zhi. 2005 Apr 13;85(14):981-5.
To investigate the expression of matrix metalloproteinase-9 (MMP-9) in the renal tissues of rats with chronic allograft nephropathy (CAN) at early stage and its role in CAN.
Orthotopic transplantation of left kidney was performed between 10 male LEW rats and 10 male F344 rats with the formers as recipients. Small dose cyclosporin A was used to suppress acute rejection. Ten days after the operation the right kidneys of the recipients were resected. Ten LEW rats and 10 F344 rats with their single kidneys resected were used as controls. Twelve weeks after the operation the rats were harvested to take out the transplanted kidneys to undergo histologic examination. Immunochemistry was used to examine the expression of MMP-9 protein and transforming growth factor (TGF)-beta1 . RT-PCR was used to examine the expression of MMP-mRNA in the kidney tissues. At the same time 24 h urine samples were collected to examine the urinary protein. The relationship between the expression of MMP-9 and TGF-beta1 and the quantity of SMCs and mononuclear cells.
The 24 h urinary protein level of the experimental group was not significantly different from those of the F3244 control group and LEW control group. The serum inosine level of the experimental group was significantly higher than that of the F334 control group and was not significantly different from that of the LEW control group. The degrees of pathologic change degree (Banff score) and fibrosis of kidney interstitium, and the number of inflammatory cells infiltrating into tubulointerstitium, arterial smooth muscle cells (SMCs) in renal cortex, and SMCs in vascular wall of the experimental group were all significantly higher than those of the 2 control groups. The expressions of MMP-9 protein and TGF-beta1 in the kidney interstitium and vascular wall and the expression of MMP-9 mRNA were all significantly higher than those of the 2 control groups. The expression of MMP-9 mRNA in kidney tissues was positively correlated with the degree of infiltration of interstitial mononuclear cells. The MMP-9 mRNA expression level was positively correlated with the number of interstitial mononuclear cells. The MMP-9 protein expression level was positively correlated with the TGF-beta1 expression level in the tubulointerstitium and in the renal arterial wall.
MMP-9 plays a key role in CAN at early stage. Its expression may be induced by TGF-beta1.
探讨基质金属蛋白酶-9（MMP-9）在慢性移植肾肾病（CAN）大鼠早期肾组织中的表达及其在CAN中的作用。
将10只雄性LEW大鼠与10只雄性F344大鼠进行左肾原位移植，LEW大鼠作为受体。使用小剂量环孢素A抑制急性排斥反应。术后10天切除受体大鼠的右肾。将10只切除单肾的LEW大鼠和10只切除单肾的F344大鼠作为对照。术后12周处死大鼠，取出移植肾进行组织学检查。采用免疫化学法检测MMP-9蛋白和转化生长因子（TGF）-β1的表达。采用逆转录-聚合酶链反应（RT-PCR）检测肾组织中MMP-9 mRNA的表达。同时收集24小时尿液样本检测尿蛋白。分析MMP-9与TGF-β1的表达与平滑肌细胞（SMC）和单核细胞数量的关系。
实验组24小时尿蛋白水平与F3244对照组和LEW对照组相比无显著差异。实验组血清肌苷水平显著高于F334对照组，与LEW对照组无显著差异。实验组肾间质病理改变程度（Banff评分）、纤维化程度、肾小管间质炎症细胞浸润数量、肾皮质动脉平滑肌细胞（SMC）数量及血管壁SMC数量均显著高于2个对照组。肾间质和血管壁中MMP-9蛋白和TGF-β1的表达以及MMP-9 mRNA的表达均显著高于2个对照组。肾组织中MMP-9 mRNA的表达与间质单核细胞浸润程度呈正相关。MMP-9 mRNA表达水平与间质单核细胞数量呈正相关。肾小管间质和肾动脉壁中MMP-9蛋白表达水平与TGF-β1表达水平呈正相关。
MMP-9在CAN早期起关键作用。其表达可能由TGF-β1诱导。
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