Yoshida Mai, Nakamichi Takashi, Mori Takefumi, Ito Kenta, Shimokawa Hiroaki, Ito Sadayoshi
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Clin Exp Nephrol. 2019 May;23(5):597-605. doi: 10.1007/s10157-019-01689-7. Epub 2019 Jan 7.
Low-energy extracorporeal shock wave (SW) improves ventricular function in ischemic cardiomyopathy through the upregulation of vascular endothelial growth factor (VEGF). VEGF is known to play important roles in acute kidney injury (AKI), and the present study investigates the efficacy of SW for AKI by renal ischemia-reperfusion (I/R) injury.
Male 8-week-old Sprague-Dawley rats were divided into the following groups: SW-treated I/R group (I/R-SW), untreated I/R group (I/R), and Sham group. To induce I/R, the left renal pedicles were clamped for 45 min. The I/R-SW group was treated with SW to both kidneys on the immediate postoperative period (day 0), days 1, 2, 7, 8, 9, 14, 15, and 16. Rats were killed on day 2 and day 20 to determine histology, renal function, and Vegf family mRNA expression.
Plasma creatinine on day 2 was significantly lower in the I/R-SW group than in the I/R group. Light microscopy revealed significantly lower tubular injury scores for the outer medulla in the I/R-SW group than in the I/R group. Podoplanin-positive lymphatic vessels were significantly increased in the left (affected side) outer medulla in the I/R-SW group on day 20. The expression levels of Vegf in the right (intact side) cortex were significantly higher in the I/R-SW group than in the I/R group on day 2.
Shock wave ameliorated renal tubular injury and renal function in AKI model, through the stimulation of Vegf family expression and lymphangiogenesis. SW may be effective as a non-invasive treatment for ischemic AKI.
低能量体外冲击波(SW)通过上调血管内皮生长因子(VEGF)改善缺血性心肌病患者的心室功能。已知VEGF在急性肾损伤(AKI)中发挥重要作用,本研究旨在探讨SW对肾缺血再灌注(I/R)损伤所致AKI的疗效。
将8周龄雄性Sprague-Dawley大鼠分为以下几组:SW治疗的I/R组(I/R-SW)、未治疗的I/R组(I/R)和假手术组。为诱导I/R,夹闭左肾蒂45分钟。I/R-SW组在术后即刻(第0天)、第1、2、7、8、9、14、15和16天对双肾进行SW治疗。在第2天和第20天处死大鼠,以确定组织学、肾功能和Vegf家族mRNA表达。
I/R-SW组第2天的血浆肌酐水平显著低于I/R组。光学显微镜检查显示,I/R-SW组外髓质的肾小管损伤评分显著低于I/R组。第20天,I/R-SW组左(患侧)外髓质中podoplanin阳性淋巴管显著增加。第2天,I/R-SW组右侧(未受损侧)皮质中Vegf的表达水平显著高于I/R组。
冲击波通过刺激Vegf家族表达和淋巴管生成,改善了AKI模型中的肾小管损伤和肾功能。SW可能作为缺血性AKI的一种非侵入性治疗方法有效。