NGAL、MMP-9及TIMP-1在单侧输尿管梗阻大鼠肾组织中的表达

Expression of NGAL, MMP-9 and TIMP-1 in Renal Tissues of Rats with Unilateral Ureteral Obstruction

目的:动态观测单侧输尿管梗阻大鼠肾组织中中性粒细胞相关脂质运载蛋白(NGAL)、基质金属蛋白酶-9(MMP 9)及金属蛋白酶组织抑制因子(TIMP-1)的表达变化,探讨NGAL分子在肾小管间质纤维化发展中的作用机制。方法:将48只雄性SD大鼠随机分为UUO模型组及假手术(SOR)组,每组24只,UUO组行左侧输尿管梗阻术,SOR组仅游离左侧输尿管不结扎。术后第1、4、7、14天分别处死每组6只大鼠,取左肾行HE&Masson染色,并用免疫组化ELiVision^(TM)-plus法检测肾组织NGAL、MMP-9及TIMP-1的表达。结果:HE、Masson染色切片示:UUO组间质损伤指数在术后各时间点高于SOR组(P<0.05)。免疫组化结果显示:UUO组术后各时间点NGAL表达高于SOR组(P<0.05),与肾小管损伤指数呈明显负相关;MMP-9在UUO术后早期(1～7天)有所上升,随着病程进展,7～14天表达有所下降;TIMP-1在UUO术后表达逐渐增强;NGAL与MMP-9/TIMP-1比值呈明显正相关。结论:NGAL在肾间质纤维化早期发挥负向调节作用,对调节MMP-9/TIMP-1的平衡亦发挥重要作用。

Objective： To observe the expression of neutrophil gelatinase-associated lipocalin（NGAL）, matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） in renal tubular interstitium of unilateral ureteral obstruction （UUO） rats, and to investigate the role of NGAL in the development of renal interstitial fibrosis. Methods：Forty-eight male Sprague Dawley rats were randomly divided into two groups： the unilateral ureteral obstruction group （UUO） and the sham-operated one （SOR）. The left ureter of the rats in UUO group was obstructed, while that of SOR group was not. Six rats of each group were respectively executed on the 1st, 4th, 7th and 14th day after surgery. Histological changes in renal tubular interstitium were observed with HE and Masson staining, and the expression of NGAL, MMP-9 and TIMP-1 in renal tissues was detected by ELiVision^TM- plus at each time point. Results： The injury index of renal interstitial tissues in UUO group was higher than that of SOR group at each time point（P〈0.05）. The results of immunobistochemistry revealed that the expression of NGAL of UUO group was higher than that of SOR group at each time point（P〈0.05）, which was also negatively correlated with the injury index of renal interstitial tissues. The expression of MMP-9 increased from 1st to 7th day, but decreased from 7th to 14th day. The expression of TIMP-1 in renal tissues increased gradually after unilateral ureteral obstruction. There was positive correlation between NGAL and the relative value of MMP- 9/TIMP-1. Conclusions：NGAL plays negative roles in the process of renal interstitial fibrosis, and also plays important roles in regulating the balance of MMP-9/TIMP-1.