Reungjui Sirirat, Roncal Carlos A, Sato Waichi, Glushakova Olena Y, Croker Byron P, Suga Shin-Ichi, Ouyang Xiaosen, Tungsanga Kriang, Nakagawa Takahiko, Johnson Richard J, Mu Wei
Division of Nephrology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
J Am Soc Nephrol. 2008 Jan;19(1):125-34. doi: 10.1681/ASN.2007030261.
Hypokalemic nephropathy is associated with alterations in intrarenal vasoactive substances, leading to vasoconstriction, salt-sensitivity, and progression of interstitial fibrosis. In this study, we investigated whether hypokalemic nephropathy might also involve impaired renal angiogenesis. Sprague-Dawley rats that were fed low-potassium diets developed peritubular capillary loss that began in the inner stripe of the outer medulla (week 2) and progressed to the outer stripe of the outer medulla (week 4) and cortex (week 12). These changes were associated with increased macrophage infiltration, increased expression of both monocyte chemoattractant protein-1 and TNF-alpha, and a loss of vascular endothelial growth factor and endothelial nitric oxide synthase. Renal thiobarbituric acid-reactive substances, markers of oxidative stress, were increased late in disease. In conclusion, hypokalemic nephropathy is associated with impaired renal angiogenesis, evidenced by progressive capillary loss, reduced endothelial cell proliferation, and loss of VEGF expression.
低钾性肾病与肾内血管活性物质的改变有关，导致血管收缩、盐敏感性增加以及间质纤维化进展。在本研究中，我们调查了低钾性肾病是否也可能涉及肾血管生成受损。喂食低钾饮食的Sprague-Dawley大鼠出现了肾小管周围毛细血管丢失，这种丢失始于外髓质内带（第2周），并进展至外髓质外带（第4周）和皮质（第12周）。这些变化与巨噬细胞浸润增加、单核细胞趋化蛋白-1和肿瘤坏死因子-α的表达增加以及血管内皮生长因子和内皮型一氧化氮合酶的丢失有关。肾硫代巴比妥酸反应性物质（氧化应激标志物）在疾病后期增加。总之，低钾性肾病与肾血管生成受损有关，表现为毛细血管逐渐丢失、内皮细胞增殖减少以及血管内皮生长因子表达丧失。
