明胶酶B及其抑制物与大鼠肾脏衰老关系的研究

目的　探讨明胶酶B(MMP 9)及其抑制物 (TIMP 1)在大鼠肾脏衰老过程中的作用。方法　选用 3月、12月、2 4月龄大鼠 ,采用免疫组化技术分别检测MMP 9、TIMP 1、Ⅲ型胶原 (ColⅢ )、纤连蛋白 (FN)、增殖细胞核抗原 (PCNA)及α 平滑肌肌动蛋白 (α SMA)在不同鼠龄大鼠肾组织中的表达。结果　TIMP 1主要表达在肾小球、小管间质及血管 ,并随增龄表达增强 (P <0 0 1) ;MMP 9、主要表达在肾小管上皮细胞 ,随增龄表达无变化 ;ColⅢ主要表达在肾小球及小管间质 ,随增龄表达增强 (P <0 0 1) ;FN主要表达在肾小球及小管间质 ,随增龄表达增强 (P <0 0 1) ;α SMA除正常在血管平滑肌表达以外 ,在 2 4月鼠肾间质纤维化部位、肾小球系膜细胞及增厚的包曼氏囊有阳性表达 ;PCNA在 2 4月鼠肾小球、肾小管的细胞核及肾间质纤维化部位的成纤维细胞核有表达。TIMP 1与肾小球硬化有相关性 (P <0 0 5 )。TIMP 1与小管间质纤维化面积有相关性 (P <0 0 5 )。结论　MMP 9/TIMP 1表达失衡在大鼠肾脏衰老过程中可能起重要作用。

THE SIGNIFICANCE OF IMBALANCE BETWEEN GELATINASE B AND TISSUE TPYE INHIBITOR OF METALLOPROTEINASE-1 DURING THE PROCESS OF AGING IN KIDNEY OF RATS

Objective To investigate the expression and role of Gelati na se B (MMP-9) and tissue type inhibitor of metalloproteinase-1 (TIMP-1) in the aging process of rats kidney.Methods Immunohistochemical ass ays were applied to detect the expression of TIMP-1, MMP-9, collagensⅢ(Col Ⅲ ), fibronectin(FN), proliferating cell nucleus antigen (PCNA), and (α-smooth m uscle actin (α-SMA) in renal tissue of rats. The rats were divided into 3 grou ps(n=8): three-month-old group(3 m), twelve-month-old group (12 m) and t wenty-four-month-old group (24 m).Results TIMP-1 was dete cted in tubulointerstitia, periglomerular and perivascular regions, and increase d signinificantly with aging (P<0.01). MMP-9 was detected in tubular epit helial cells. No change of the expression of MMP-9 was found among the 3 groups . The expression of CoⅢ was signinificantly increased in renal tissue of 24 m r ats (P<0.01). The expression of FN was signinificantly increased in renal tissue of 24 m rats (P<0.01). α-SMA was normally detected only in vascul ar walls, but also detected in mesangial cells, thickened Bowman, capsule and in terstitium of 24 m rats. PCNA positive cells were found in tubulointers titial cells and tubular epithelial cells of renal tissue of 24 m rats. TIMP-1 had positive correlations with glomerulos clerosis (P<0.05). TIMP-1 had positive correlations with interst itial fibrosis area(P<0.05).Conclusion The imbalance be tween metalloproteinases and tissue type inhi-bitor of metalloproteinases may p lay an important role during the process of aging in kidney of rats.