Renal Diseases and Hypertension, School of Medicine, University of Colorado ANSCHUTZ MEDICAL CAMPUS, Aurora, Colorado, 80045, USA.
Department of Pathology, School of Medicine, University of Colorado ANSCHUTZ MEDICAL CAMPUS, Aurora, Colorado, 80045, USA.
Sci Rep. 2017 Aug 29;7(1):9793. doi: 10.1038/s41598-017-09470-0.
Serelaxin, a recombinant form of the naturally occurring peptide hormone relaxin-2, is a pleiotropic vasodilating hormone that has been studied in patients with acute heart failure. In this study, the effects of serelaxin on cardiac and renal function, fibrosis, inflammation and lipid accumulation were studied in DOCA-salt treated rats. Uninephrectomized rats were assigned to two groups: controls provided with normal drinking water and DOCA provided with DOCA pellets and sodium chloride drinking water. After 4 weeks, the DOCA-salt rats were randomly selected and implanted with osmotic minipumps delivering vehicle or serelaxin for another 4 weeks. Treatment with serelaxin prevented cardiac and renal dysfunction in DOCA-salt rats. Serelaxin prevented cardiac and renal fibrosis, as determined by Picrosirius Red staining and Second Harmonic Generation (SHG) Microscopy. Treatment of DOCA-salt rats with serelaxin decreased renal inflammation, including the expression of TGF-β, NFκB, MCP-1, IL-1, IL-6, ICAM-1, VCAM-1 and CD68 macrophages. Serelaxin also decreased lipid accumulation in kidney in part by decreasing SREBP-1c, SREBP-2, ChREBP, FATP1, HMGCoAR, and LDL receptor, and increasing Acox1 and ABCA1. In summary, serelaxin reversed DOCA-salt induced cardiac and renal dysfunction.
Serelaxin，一种天然存在的激素松弛素-2 的重组形式，是一种多效性血管舒张激素，已在急性心力衰竭患者中进行了研究。在这项研究中，研究了 Serelaxin 对 DOCA-盐处理的大鼠心脏和肾功能、纤维化、炎症和脂质积累的影响。单侧肾切除大鼠分为两组：对照组提供正常饮用水，DOCA 组提供 DOCA 丸和氯化钠饮用水。4 周后，随机选择 DOCA-盐大鼠，并植入输送载体或 Serelaxin 的渗透微型泵再治疗 4 周。Serelaxin 可预防 DOCA-盐大鼠的心脏和肾功能障碍。Serelaxin 可预防心脏和肾脏纤维化，如通过苦味酸红染色和二次谐波产生（SHG）显微镜确定。Serelaxin 治疗 DOCA-盐大鼠可减少肾脏炎症，包括 TGF-β、NFκB、MCP-1、IL-1、IL-6、ICAM-1、VCAM-1 和 CD68 巨噬细胞的表达。Serelaxin 还通过减少 SREBP-1c、SREBP-2、ChREBP、FATP1、HMGCoAR 和 LDL 受体，增加 Acox1 和 ABCA1，部分减少了肾脏中的脂质积累。总之，Serelaxin 逆转了 DOCA-盐诱导的心脏和肾功能障碍。
