Mammalian target of rapamycin inhibition halts the progression of proteinuria in a rat model of reduced renal mass
Mammalian target of rapamycin inhibition halts the progression of proteinuria in a rat model of reduced renal mass
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DOI：
10.1681/asn.2007010087
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发表时间：
2007-10-01
影响因子：
13.6
通讯作者：
Campistol, Josep M.
中科院分区：
文献类型：
--
作者：
Diekmann, Fritz;Rovira, Jordi;Campistol, Josep M.
当从基于钙调神经磷酸酶抑制剂的治疗方案转换为基于哺乳动物雷帕霉素靶点 (mTOR) 抑制剂的治疗方案时，许多肾移植患者会出现蛋白尿增加，而先前存在的蛋白尿和肾功能不良已被确定为这种增加的危险因素。我们的目的是在肾质量减少的蛋白尿模型中评估西罗莫司（一种 mTOR 抑制剂）对肾功能和组织学的影响。西罗莫司治疗的动物的蛋白尿大约是媒介物治疗的动物的一半（P < 0.05），并且肾小球硬化、肾小管萎缩、间质纤维化和炎症较少。免疫组织化学显示，西罗莫司可减弱肾血管内皮生长因子 (VEGF) 表达的增加，以及 VEGF 受体 1 和 2 的表达。总之，西罗莫司可能通过降低肾 VEGF 活性来阻止肾质量减少的大鼠模型中蛋白尿和结构损伤的进展。
Many kidney transplant patients experience an increase in proteinuria when converted from a calcineurin inhibitor-based regimen to one based on a mammalian target of rapamycin (mTOR) inhibitor, and preexisting proteinuria and poor renal function have been identified as risk factors for this increase. Our aim was to evaluate the effect of sirolimus, an mTOR inhibitor, on renal function and histology in a proteinuric model of reduced renal mass. Sirolimus-treated animals had approximately half as much proteinuria as vehicle-treated animals (P < 0.05), and had less glomerulosclerosis, tubular atrophy, interstitial fibrosis, and inflammation. Immunohistochemistry showed that sirolimus attenuated the increased expression of renal vascular endothelial growth factor (VEGF), as well as the expression of VEGF receptors 1 and 2. In conclusion, sirolimus halted the progression of proteinuria and structural damage in a rat model of reduced renal mass, possibly through a reduction in renal VEGF activity.