摘要
目的研究纤溶酶原激活物抑制剂1(PAI-1)和组织基质金属蛋白酶抑制剂1(TIMP-1)基因表达与梗阻性肾病小管间质纤维化(TIF)进展的关系及肝细胞生长因子(HGF)的干预作用。方法60只Wistar大鼠随机分为4组正常大鼠组、假手术组、单侧输尿管梗阻组和HGF治疗组,分别于模型3d、7d、14d、21d处死大鼠。采用逆转录多聚酶链反应(RT-PCR)检测PAI-1和TIMP-1mRNA表达水平;底物酶谱法检测肾脏MMP2、9活性的变化,测定肾组织羟脯氨酸含量判断纤维化程度。结果梗阻肾组织PAI-1和TIMP-1mRNA表达显著高于对照组,并伴有明显的梗阻肾MMP2,MMP9活性低于和羟脯氨酸含量高于对照组,而21dHGF治疗组PAI-1和TIMP-1mRNA表达明显下调,MMP2,MMP9活性高于和肾组织羟脯氨酸含量少于对照组。结论PAI-1、TIMP-1mRNA表达增高是小管间质ECM降解减少的主要原因之一,也是造成TIF加重的重要因素,而HGF可拮抗这一进程,减轻小管间质纤维化。
AIM: The aim of this study was to determine the relationship between PAI-1,TIMP-1 gene expression and renal tubulointerstitial fibrosis(TIF) of ureteral obstruction ,and the interfering effects of hepatocyte growth factor (HGF) treatment. METHODS: Sixty rats were divided into normal control, sham operation,unilateral ureteral obstruction(UUO),and rhHGF treated groups (received 0 5 mg·kg -1 ·d -1 HGF for twenty-one days), and were sacrificed at postoperative day 3, 7, 14, 21. The levels of PAI-1, TIMP-1 mRNA were measured by RT-PCR. MMP2 and MMP9 activities were detected by substrate zymography, and renal fibrosis was assessed by measuring tissue hydroxyproline. RESULTS: Compared to controls, expression levels of PAI-1,TIMP-1 mRNA were significantly increased in UUO rats, and this was accompanied by decreased activities of MMP2 and MMP9 and increase in tissue hydroxyproline content. HGF treatment significantly decreased expressions of PAI-1, TIMP-1 mRNA, increased MMP2 and MMP9 activities,and decreased tissue hydroxyproline content in the obstructive kidney. CONCLUSIONS: These results indicate that the increases in PAI-1, TIMP-1 mRNA expression may be the major cause of sustained decreased matrix degradation during the development of tubulointerstitial fibrosis after unilateral ureteral obstruction. rhHGF efficiently ameliorates renal tubulointerstitial injury by the reduction of PAI-1,TIMP-1 mRNA expression, and increasing MMP2, MMP9 activities. [
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2004年第9期1542-1546,共5页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.30100083)
全军十五医药卫生青年科研基金课题(No.01Q103)
关键词
纤维蛋白溶解原1
金属蛋白酶Ⅰ组织抑制剂
转化生长因子Β
肝细胞生长因子
肾小管
纤维化
Plasminogen activator inhibitor 1
Tissue-inhibitor of metalloproteinase-1
Transforming growth factor beta
Hepatocyte growth factor
Kidney tubules
Fibrosis
