东篱科研大数据发现系统（DRDS）

位置：成果数据库 > 期刊 > 期刊详情页

人基质金属蛋白酶1组织抑制剂转基因小鼠肾小管间质炎症的改变

ISSN号：1001-7097
期刊名称：《中华肾脏病杂志》
时间：0
分类：R692.6[医药卫生—泌尿科学;医药卫生—临床医学;医药卫生—外科学]
作者机构：[1]解放军总医院肾科全军肾脏病研究所暨重点实验室,北京100853
相关基金：国家自然科学基金创新群体科学基金（30121005）;国家自然科学基金（30300161）;北京市自然科学基金（7032045）.“973”项目（2007C13507400）

作者：邵凤民[1], 尚希瑶[1], 张雪光[1], 蔡广研[1], 师锁柱[1], 尹忠[1], 吕扬[1], 洪权[1], 陈香美[1]

关键词：转基因, 金属蛋白酶1组织抑制剂, 细胞黏附分子, 炎症, 输尿管梗阻, Transgenes , Tissue inhibitor of metalloproteinase- 1 , Cell adhesion molecules , Inflammation , Ureteral obstruction

中文摘要：

目的观察基质金属蛋白酶1组织抑制剂（TIMP-1）过表达对肾小管间质炎症反应的影响。方法采用人TIMP-1转基因小鼠和野生型小鼠（n=8）构建单侧输尿管梗阻（UUO）模型。以3d和14d为时间点，Masson染色观察肾组织形态学变化，间接免疫荧光法观察肾组织内F4／80阳性细胞的表达：Western印迹检测TIMP-1、TIMP-2、MMP-2、MMP-9和ICAM-1的蛋白表达．明胶酶谱法检测MMP-2和MMP-9的活性，反向酶谱法检测TIMP-1的活性。结果 UUO术后肾小管间质病理损伤加重[肾间质纤维化面积（46．24±6．58）％比野生型（36．33±5．12）％，P〈0．05]，F4／80阳性细胞数目增加[（68．9±15．6）个／视野比野生型（52．4±13．3）个／视野，P〈0．05]，ICAM-1蛋白表达显著上调，术后14d上述改变在转基因组中更为显著（P〈0．05）。UUO术后TIMP-1蛋白表达及活性上调，在术后14d达高峰，在转基因组中增加更为显著（P〈0．05）。MMP-2和MMP-9的蛋白表达及活性在术后逐渐下降，UUO术后14d转基因组降低更为显著（P〈0．05）。结论 TIMP-1过表达可通过增强炎症加重肾小管间质损伤。

英文摘要：

Objective To observe the effects of TIMP-1 overexpression on renal tubulointerstitial inflammation. Methods Human TIMP-1 transgenic mice and wild-type mice were randomly divided into UUO groups and sham groups respectively and sacrificed at 3 and 14 days after UUO or sham operation （n=6, each group）. Masson staining was applied to observe the renal tubulointerstitial pathological changes,and indirect immunofluorescence was applied to detect F4/80 positive cells. Westem blot was applied to analyze the protein expression of TIMP-1, TIMP-2, MMP-2, MMP-9 and ICAM-1. The activities of gelatinase and TIMP-1 were detected by gelatin zymography and reverse zymography respectively. Results The degree of renal tubulointerstitial fibrosis [ fibrosis area：trangenes （46.24±6.58）% vs wild-type （36.33±5.12）% ,P 〈 0.05], the number of positive F4/80 cells [trangenes（68.9±15.6） vs wild-type （52.4±13.3）cell/field,P 〈 0.05], and the protein expression of ICAM-1 were increased after UUO, which were more significant in transgenic group than in wildtype group at day 14 after UUO （P 〈 0.05）. The protein expression and activity of TIMP-1 were increased significantly after UUO and with a maximum at day 14 after UUO, and were higher in transgenic group than in wild-type group（P 〈 0.05）. The protein expression and activities of MMP-2 and MMP-9 were decreased after UUO, and were lower in transgenic group than in wild-type group at day 14 after UUO （P 〈 0.05）. Conclusions Overexpression of TIMP-1 exacerbates renal tubulointerstitial injury by enhancing inflammation.

同期刊论文项目