组织金属蛋白酶抑制物在老年大鼠肾小管间质病理损害中的动态变化  

The expression and significance of matrix metalloproteinases and tissue type inhibitor of metalloproteinases in renal tubulointerstitial pathological lesion of aging rats

作　　者：陈荣权[1] 陈香美[1] 崔世维[1] 蔡广研[1] 师锁柱[1] 谢院生[1] 吕杨[1] 彭丽霞[1] 

机构地区：[1]解放军总医院肾病科解放军肾病中心暨重点实验室,北京100853

出　　处：《中华老年医学杂志》2004年第4期253-258,共6页Chinese Journal of Geriatrics

基　　金："973"项目资助 (G2 0 0 0 0 5 70 0 3 );国家自然科学基金"创新研究群体"项目资助(3 0 12 10 0 5 );北京市自然科学基金资助项目(编号 :70 3 2 0 45 )

摘　　要：目的　研究组织金属蛋白酶抑制物 (TIMPs)及基质金属蛋白酶 (MMPs)在不同鼠龄单侧输尿管梗阻 (UUO)大鼠肾小管间质中的表达变化 ,探讨其在老年大鼠肾小管间质损害中的作用。　方法　选用 3月龄 (青年 )、2 6月龄 (老年 )大鼠制备UUO模型 ,采用病理及免疫组化等方法动态观察不同年龄大鼠UUO术后 3、7、14d梗阻侧肾脏的组织学变化和TIMP 1、TIMP 2、MMP 2、MMP 9等在梗阻肾小管间质中的表达情况。　结果　TIMP 1、TIMP 2及MMP 2、MMP 9主要表达于肾小管上皮细胞和间质细胞。在对照组中 ,TIMP 1、TIMP 2仅微弱表达于青年鼠肾脏中 ,而在老年大鼠肾脏中其表达显著增加 (TIMP 10 84± 0 2 3vs 2 17± 0 85 ,P <0 0 1;TIMP 2 0 93± 0 12vs 2 31± 0 87,P <0 0 1) ,MMP 2、MMP 9在正常青年鼠与老年鼠肾脏中均有表达 ,二者之间差异无显著性(P >0 0 5 )。与对照组相比 ,3、2 6月龄大鼠梗阻侧肾脏的TIMP 1、TIMP 2及MMP 2、MMP 9在术后各时间点的表达均显著增高 (P <0 0 1) ,肾小管间质纤维化面积随UUO术后时间的延长而增加 ,且TIMP 1、TIMP 2的表达与肾小管间质纤维化面积呈正相关 (TIMP 1,r =0 816 ,P <0 0 1;TIMP 2 ,r =0 85 1,P <0 0 1)。与 3月龄UUO大鼠比较 ,2 6月龄UUO大鼠TIMP 1、TIMP 2?Objective The aim of this study is to explore the expression of tissue type inhibitor of metalloproteinases(TIMPs) and matrix metalloproteinases(MMPs) in renal tubulointerstitial lesion of aging rats induced by unilateral ureteral obstruction (UUO) and its role during the progress of renal tubulointerstitial lesion Methods The UUO model and the control group were made with 3 month old rats and 26 month old rats respectively, and 8 rats of each group were sacrificed at 3, 7, 14 days, respectively Then histopathological method was applied to observe the histologic changes of obstructive kidney and immunohistochemistry was used to detect the expression of TIMP 1, TIMP 2, MMP 2 and MMP 9 in the UUO rat kidneys of different age at each time point Results TIMP 1, TIMP 2, MMP 2 and MMP 9 were mainly expressed in tubular epithelial cells and interstitial cells In control groups,TIMP 1 and TIMP 2 were poorly expressed in kidney of 3 month old rats, and were significantly increased in the aged rat kidneys (TIMP 1 0 84±0 23 vs 2 17±0 85, P <0 01; TIMP 2 0 93±0 12 vs 2 31±0 87, P <0 01, respectively), no difference was found about the expression of MMP 2 and MMP 9 between two groups since they were normally expressed in either young and old rat kidneys Compared with the control group, the expression of TIMP 1, TIMP 2, MMP 2 and MMP 9 in UUO rat kidneys were significantly increased at each time point( P <0 01); and the renal tubulointerstitial fibrotic areas were increased with the prolonging of UUO, furthermore, the expression of TIMP 1 and TIMP 2 were positively correlated with renal tubulointerstitial fibrotic areas(TIMP 1, r =0 816, P <0 01; TIMP 2, r =0 851, P <0 01) Compared with 3 month old rats, the expression of TIMP 1, TIMP 2 in UUO kidneys of 26 month old rats was significantly higher at each time point( P <0 01), and the relative renal interstitial areas and tubulointerstitial fibrotic areas were also increased

关 键 词：组织金属蛋白酶抑制物 老年大鼠 肾小管间质 病理损害 免疫组化法 输尿管梗阻 

分 类 号：R692.6[医药卫生—泌尿科学]