Departments of Nephrology, Dokuz Eylul University School of Medicine, Balcova, Turkey.
Nephrology (Carlton). 2010 Aug;15(5):560-7. doi: 10.1111/j.1440-1797.2010.01289.x.
Renal expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMP (TIMP) contribute to the development of tubulointerstitial fibrosis characteristic of progressive forms of primary glomerulonephritis (GN). The aim of this study was to investigate the therapeutic effect of MMP inhibitor, doxycycline, administration in an experimental rat model of immune-complex nephritis (ICN).
The induction of immune-complex glomerulonephritis was carried out by the administration of an i.v. dose of 2 mg bovine serum albumin (BSA) daily for 28 days after 8 weeks of s.c. immunization with 1 mg of BSA in complete Freund's adjuvant. Doxycycline (30 mg/kg) was given daily (in groups 2 and 4) by gavage for 28 days.
Animals treated with doxycycline showed significant reduction in glomerular area and cell proliferation than non-treated controls. Glomerular deposition of immunoglobulin (Ig)G and C3 was less intense in treated rats than non-treated controls. Although not statistically significant, interstitial inflammation was less intense in treated rats than non-treated controls. Glomerular expression of MMP-9 by immunoflourescence was significantly inhibited in the treated group. In addition pro-MMP-2 on gelatin zymography was importantly suppressed by doxycycline in ICN.
Doxycycline, in addition to its antibiotic property, may, following further investigation, provide a possible survival benefit in proliferative glomerulonephritis.
基质金属蛋白酶（MMP）和金属蛋白酶组织抑制剂（TIMP）在肾小管间质纤维化的发展中起作用，这种纤维化是原发性肾小球肾炎（GN）进行性形式的特征。本研究的目的是研究基质金属蛋白酶抑制剂强力霉素在免疫复合物肾炎（ICN）实验大鼠模型中的治疗效果。
通过静脉内给予 2 毫克牛血清白蛋白（BSA），在皮下用完全弗氏佐剂免疫 1 毫克 BSA 8 周后，每天给予 28 天，诱导免疫复合物性肾炎。强力霉素（30mg/kg）每天通过灌胃给予（在第 2 组和第 4 组）28 天。
与未治疗的对照组相比，用强力霉素治疗的动物的肾小球面积和细胞增殖明显减少。用强力霉素治疗的大鼠肾小球 IgG 和 C3 的沉积比未治疗的对照组少。虽然没有统计学意义，但治疗组的间质炎症比未治疗的对照组少。用免疫荧光法检测到肾小球 MMP-9 的表达明显受到抑制。此外，在 ICN 中，强力霉素还显著抑制了明胶酶谱中的 pro-MMP-2。
除了其抗生素特性外，强力霉素可能在进一步研究后为增殖性肾小球肾炎提供可能的生存益处。
