摘要
目的观察Ets-1、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-1组织抑制剂(TIMP-1)和胶原Ⅲ在实验性顺铂相关性肾病中的表达,并探讨其意义。方法6周雄性W istar大鼠被随机分成两组:顺铂组(n=20),顺铂6 mg.kg-1腹腔内单次注射;对照组(n=12),同等剂量生理盐水注射。注射后1、3、7、14 d处死各组动物,每次顺铂组5只,对照组3只。结果顺铂组在顺铂注射后第3、7、14天出现肾功能不全,在第3、7天肾小管上皮细胞出现变性、坏死、凋亡及间质内炎症细胞浸润,第14天可见明显肾间质纤维化形成。与对照组比较,Ets-1在肾小管间质内的表达在顺铂注射后第3天明显增加(P<0.05),第7、14天则明显减少(P<0.01);MMP-1表达呈现相似形式,顺铂注射后第3日明显增加(P<0.01);而TIMP-1表达在顺铂处理后第1、3天无明显变化,第7、14天则明显增加(P<0.01);MMP-1/TIMP-1在顺铂注射后第1天即明显升高(P<0.01),第3天升高更为明显(P<0.001),第7、14天则明显下降,与顺铂注射后第3天相比,差异有统计学意义(P<0.001);胶原Ⅲ沉积在顺铂处理后第7、14天则逐渐增加(P<0.05,P<0.01)。统计学分析显示,肾小管间质内Ets-1表达同MMP-1的表达呈正相关(r=0.78,P<0.01),同TIMP-1的表达呈负相关(r=-0.639,P<0.01),而同MMP-1/TIMP-1呈正相关(r=0.925,P<0.001)。肾小管间质内Ets-1表达与胶原Ⅲ的表达呈负相关(r=-0.599,P<0.01);MMP-1/TIMP-1与胶原Ⅲ的表达呈负相关(r=-0.631,P<0.01)。免疫双染结果表明,Ets-1阳性肾小管上皮细胞同时具有MMP-1阳性表达;肾小管上皮细胞TIMP-1表达增加处肾间质区域内同时存在胶原Ⅲ大量沉积。结论Ets-1转录因子可能通过调节MMP-1与TIMP-1酶系统的平衡,对胶原蛋白在肾间质内沉积产生影响,在顺铂相关性肾病基质重塑过程中起关键性作用。
Objective To study the role of Ets-1, metalloproteinase-1 （ MMP- 1 ）, tissue inhibitor of metalloproteinase-1 （TIMP-1 ） and interstitial type Ⅲ collagen in matrix remodeling in experimental cisplatin nephropathy. Methods Six-week-old male Wistar rats （ n = 32） were divided into two groups. Rats in control group （n = 12） injected with normal saline,while rats in cisplatin group （n = 20） were treated with a single intraperitoneal injection of cisplatin （6 mg·kg^-1 ）. rats were killed on days 1,3,7 and 14. Results In contrast to kidneys obtained from control rats, kidneys of cisplatin-treated rats showed features of tubular regeneration, necrosis, apoptosis, inflammatory cells infiltration, and occasional dilatation of tubular lumina in eorticomedullary areas on days 3 and 7. In addition, interstitial fibrosis was noted in kidneys obtained from eisplatin-treated rats on day 14. Compared with control rats, Ets-1 positive cells significantly increased in tubular epithelial cells and interstitial cells in the kidneys of eisplatin-treated rats on day 3 （ P 〈 0.05 ）, decreased on days 7 （ P 〈 0. 01 ） and 14 （P 〈0.01 ）. The expression of MMP-1 on tubulointerstitium showed a similar pattern,significantly increased on day 3 （P 〈0.01 ） in contrast to the same time point of control rat kidneys,but deereased on days 7 （P 〈0.01 ） and 14 （P 〈0.01 ）. Compared with control, the expression of TIMP-1 on tubulointerstitium significantly increased ratio of MMP- 1 and TIMP- 1 on days 7 （ P 〈 0.01 ） and 14 （ P 〈 0.01 ）. Compared with control rat kidneys, the on tubulointertitium began to increase on day 1 （ P 〈 0.01 ） of cisplatin-treated rat kidneys, and significantly increased on day 3 （ P 〈 0. 001 ）. In cisplatintreated rats the ratio of MMP- 1 and TIMP-1 was significantly decreased on days 7 and 14 ,when compared contol rat kindeys,interstitial accumulation of type Ⅲ collagen began with day 3 （ P 〈0.001 ）. Compared with to increase on day
出处
《现代医学》
2008年第5期301-305,共5页
Modern Medical Journal
