From the Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (Y.A., A.N., K.-i.K., F.M.Y., F.M., S.K., T.M., Y.H.), Hiroshima University.
Department of Stem Cell Biology and Medicine, Graduate School of Biomedical and Health Sciences (A.N.), Hiroshima University.
Hypertension. 2020 Dec;76(6):1906-1914. doi: 10.1161/HYPERTENSIONAHA.120.15237. Epub 2020 Nov 2.
The estimated morbidity rate of chronic kidney disease is 8% to 16% worldwide, and many patients with chronic kidney disease eventually develop renal failure. Thus, the development of new therapeutic strategies for preventing renal failure is crucial. In this study, we assessed the effects of daily low-intensity pulsed ultrasound (LIPUS) therapy on experimental hypertensive nephropathy and diabetic nephropathy. Unilateral nephrectomy and subcutaneous infusion of angiotensin II via osmotic mini-pumps were used to induce hypertensive nephropathy in mice. Immunohistochemistry revealed that daily LIPUS treatment ameliorated renal fibrosis and infiltration of inflammatory cells induced by angiotensin II. A similar therapeutic effect was also observed in mice with angiotensin II-induced hypertensive nephropathy in which splenectomy was performed. In addition, LIPUS treatment significantly decreased systolic blood pressure after 21 days. Subsequently, mice with unilateral nephrectomy developed proteinuria; daily LIPUS treatment significantly reduced proteinuria after 42 days. In addition, immunohistochemistry revealed that renal fibrosis was significantly ameliorated by LIPUS treatment. Finally, LIPUS stimulation suppressed TGF-β1 (transforming growth factor-β1)-induced phosphorylation of Smad2 and Smad3 in HK-2 (human proximal tubular cell line) cells. LIPUS treatment may be a useful therapy for preventing the progression of renal fibrosis in patients with chronic kidney disease.
全球范围内慢性肾脏病的发病率估计为 8%至 16%，许多慢性肾脏病患者最终会发展为肾衰竭。因此，开发预防肾衰竭的新治疗策略至关重要。在这项研究中，我们评估了每日低强度脉冲超声（LIPUS）治疗对实验性高血压肾病和糖尿病肾病的影响。单侧肾切除术和通过渗透微型泵皮下输注血管紧张素 II 用于诱导小鼠高血压肾病。免疫组织化学显示，每日 LIPUS 治疗可改善血管紧张素 II 诱导的肾纤维化和炎症细胞浸润。在进行脾切除术的血管紧张素 II 诱导的高血压肾病小鼠中也观察到类似的治疗效果。此外，LIPUS 治疗可在 21 天后显著降低收缩压。随后，单侧肾切除的小鼠出现蛋白尿；42 天后，LIPUS 治疗可显著减少蛋白尿。此外，免疫组织化学显示，LIPUS 治疗可显著改善肾纤维化。最后，LIPUS 刺激抑制了 HK-2（人近端肾小管细胞系）细胞中 TGF-β1（转化生长因子-β1）诱导的 Smad2 和 Smad3 的磷酸化。LIPUS 治疗可能是预防慢性肾脏病患者肾纤维化进展的一种有用疗法。
