Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA.
Division of Nephrology & Hypertension, Mayo Clinic, Rochester, MN, USA.
Sci Rep. 2018 Jun 5;8(1):8598. doi: 10.1038/s41598-018-26870-y.
Inflammation plays an important role in the pathogenesis of renal and cardiovascular disease in renovascular hypertension (RVH). Ccl2 is an important mediator of inflammation, and is induced within 24 hours following surgery to establish RVH in the murine 2 kidney 1 clip model, a time prior to onset of interstitial inflammation, fibrosis, or tubular atrophy. We tested the hypothesis that Ccl2 deficiency protects the stenotic kidney (STK) from development of chronic renal damage in mice with renovascular hypertension due to renal artery stenosis (RAS). RAS surgery was performed on wild type (WT) and Ccl2 knock out (KO) mice; animals were studied for four weeks. Renal blood flow was reduced to similar extent in both WT and Ccl2 KO mice with RVH. Perfusion of the stenotic kidney was significantly reduced in Ccl2 KO mice as assessed by magnetic resonance imaging (MRI). Stenotic kidney volume in WT, but not in Ccl2 KO mice, was significantly reduced following surgery. Cortical hypoxia was observed in the stenotic kidney of Ccl2 KO mice, as assessed by blood oxygen level-dependent MRI (BOLD-MRI). Ccl2 KO mice showed less cortical atrophy than WT RAS mice. Ccl2 deficiency reduced the number of infiltrating mononuclear cells and expression of Ccl5, Ccl7, Ccl8, Ccr2 and Cd206. We conclude that Ccl2 is a critical mediator of chronic renal injury in RVH.
在肾血管性高血压（RVH）中，炎症在肾脏和心血管疾病的发病机制中起着重要作用。CCL2 是炎症的重要介质，在建立小鼠 2 肾 1 夹 RVH 模型的手术后 24 小时内即可诱导，此时间质炎症、纤维化或肾小管萎缩尚未发生。我们假设 CCL2 缺乏可保护狭窄肾脏（STK）免受因肾动脉狭窄（RAS）引起的 RVH 小鼠慢性肾损伤的发展。在野生型（WT）和 CCL2 敲除（KO）小鼠中进行 RAS 手术；对动物进行了 4 周的研究。RVH 中 WT 和 CCL2 KO 小鼠的肾血流均减少到相似程度。通过磁共振成像（MRI）评估，CCL2 KO 小鼠的狭窄肾脏灌注明显减少。WT 小鼠的狭窄肾脏体积在手术后明显减小，但 CCL2 KO 小鼠则不然。通过血氧水平依赖 MRI（BOLD-MRI）评估，CCL2 KO 小鼠的狭窄肾脏中观察到皮质缺氧。与 WT RAS 小鼠相比，CCL2 缺乏症小鼠的皮质萎缩程度较轻。CCL2 缺乏症减少了浸润单核细胞的数量和 CCL5、CCL7、CCL8、CCR2 和 CD206 的表达。我们得出结论，CCL2 是 RVH 中慢性肾损伤的关键介质。
