Morrissey Jeremiah, Hruska Keith, Guo Guangjie, Wang Song, Chen Qing, Klahr Saulo
Renal Division, Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri 63110-1092, USA.
J Am Soc Nephrol. 2002 Jan;13 Suppl 1:S14-21.
A prevention protocol has demonstrated that bone morphogenetic protein-7 (BMP-7) blunted the development of fibrosis in a rat model of unilateral ureteral obstruction. This prevention protocol also preserved, to an extent, renal function. The prevention protocol was extended and a treatment protocol used to examine if BMP-7 was beneficial at limiting fibrosis of the kidney when the BMP-7 was administered during the progression of fibrotic disease. Animals were distributed into four groups. Group 1 received vehicle, group 2 received enalapril (12.5 mg/kg body wt per d), group 3 received BMP-7 (50 or 300 microg/kg), and group 4 received both the enalapril and the high dose of BMP-7. Rats underwent reversible unilateral ureteral obstruction for 3 d, after which the obstruction was relieved. In the treatment protocol, 300 microg/kg BMP-7 was given after the release of obstruction. Seven days after release of the obstruction and the onset of treatment glomerular filtration rate (GFR), renal blood flow, and various histologic indexes of fibrosis were determined. On a consistent basis, BMP-7 treatment alone was found to be slightly but significantly (P < 0.04 to 0.007) better than enalapril alone or in combination with enalapril at decreasing interstitial volume or tubule atrophy. BMP-7 treatment was slightly but not significantly better (P < 0.09) than enalapril at restoring GFR in the prevention protocol. Treatment with BMP-7 significantly boosted GFR (P < 0.01) above that seen with vehicle treatment. These results suggest that BMP-7 treatment is capable of blunting the progression of fibrotic disease and of decreasing interstitial volume. Importantly, a return of renal function is accelerated by BMP-7 treatment. These results suggest that administration of BMP-7 may be an effective treatment to restore or preserve renal histology and renal function in this experimental model of renal disease.
一项预防方案已证明,骨形态发生蛋白-7(BMP-7)可抑制单侧输尿管梗阻大鼠模型中纤维化的发展。该预防方案在一定程度上还保留了肾功能。该预防方案得到了扩展,并采用了一种治疗方案来研究当在纤维化疾病进展过程中给予BMP-7时,它是否对限制肾脏纤维化有益。动物被分为四组。第1组接受赋形剂,第2组接受依那普利(每日每千克体重12.5毫克),第3组接受BMP-7(50或300微克/千克),第4组接受依那普利和高剂量的BMP-7。大鼠经历可逆性单侧输尿管梗阻3天,之后梗阻解除。在治疗方案中,梗阻解除后给予300微克/千克BMP-7。梗阻解除和开始治疗7天后,测定肾小球滤过率(GFR)、肾血流量以及纤维化的各种组织学指标。在减少间质体积或肾小管萎缩方面,一直发现单独使用BMP-7治疗比单独使用依那普利或与依那普利联合使用略好但具有显著差异(P<0.04至0.007)。在预防方案中,BMP-7治疗在恢复GFR方面比依那普利略好但无显著差异(P<0.09)。BMP-7治疗显著提高了GFR(P<0.01),高于赋形剂治疗组。这些结果表明,BMP-7治疗能够抑制纤维化疾病进展并减少间质体积。重要的是,BMP-7治疗可加速肾功能的恢复。这些结果表明,在该肾脏疾病实验模型中,给予BMP-7可能是恢复或保留肾脏组织学和肾功能的有效治疗方法。