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骨髓间充质干细胞移植可改善肾血管性高血压大鼠的肾功能和 Na+-K+-ATP 酶活性。

Transplantation of bone marrow-derived MSCs improves renal function and Na+K-ATPase activity in rats with renovascular hypertension.

机构信息

Histology and Embryology Department, Stem Cell Research Laboratory, State University of Rio de Janeiro, Av. Professor Manuel de Abreu, 444, Vila Isabel, CEP: 20.551-17, Rio de Janeiro, RJ, Brazil.

Federal University of Rio de Janeiro, Macaé - Av. Aloízio da Silva Gomes 50, Granja dos Cavaleiros, Macaé, Rio de Janeiro, Brazil.

出版信息

Cell Tissue Res. 2017 Aug;369(2):287-301. doi: 10.1007/s00441-017-2602-3. Epub 2017 Apr 3.

Abstract

Renovascular hypertension (RVH) is a progressive disease, leading to chronic kidney disease when untreated and no specific treatment is available. Therefore, development of new therapeutic modalities is imperative. RVH is triggered by renal artery stenosis and subsequent renin-angiotensin-aldosterone system activation; it can be experimentally induced by the 2 Kidneys-1 Clip (2K1C) model. This study investigates the therapeutic potential of renal subcapsular mesenchymal stem cell (MSC) infusion in 2K1C rats. Renal morphological and functional changes were analyzed, including Na+K-ATPase activity and expression, renin angiotensin-converting enzyme (ACE) and angiotensin-II type 1 (ATR) and type 2 (ATR) receptors expression. 2K1C rats developed hypertension accompanied by renin upregulation (clipped kidney) and renal Na+K-ATPase activity and expression reduction. MSC therapy decreased systolic blood pressure, renin, ACE, and ATR, upregulated ATR and podocin expression and restored renal Na+K-ATPase activity and expression. In addition, MSC improved renal morphology, reduced fibrosis and TGF-β expression in the clipped kidney, decreased proteinuria and restored protein plasma levels. In conclusion, transplantation into a renal subcapsule is an efficient route and MSC is a good candidate for cell therapy, which may represent an interesting approach for chronic kidney disease treatment.

摘要

肾血管性高血压 (RVH) 是一种进行性疾病,如果不治疗,会导致慢性肾脏病,而且目前尚无特效治疗方法。因此,开发新的治疗方法势在必行。RVH 是由肾动脉狭窄和随后的肾素-血管紧张素-醛固酮系统激活引起的;可以通过 2 肾 1 夹 (2K1C) 模型在实验中诱发。本研究探讨了肾被膜下间充质干细胞 (MSC) 输注在 2K1C 大鼠中的治疗潜力。分析了肾脏形态和功能的变化,包括 Na+K-ATP 酶活性和表达、肾素血管紧张素转换酶 (ACE) 和血管紧张素-II 型 1 (ATR) 和 2 型 (ATR) 受体的表达。2K1C 大鼠发生高血压,伴有肾素上调(夹闭肾)和肾 Na+K-ATP 酶活性和表达降低。MSC 治疗可降低收缩压、肾素、ACE 和 ATR,上调 ATR 和 podocin 表达,并恢复肾 Na+K-ATP 酶活性和表达。此外,MSC 改善了肾脏形态,减少了夹闭肾脏中的纤维化和 TGF-β 表达,减少了蛋白尿并恢复了蛋白质血浆水平。总之,肾被膜下移植是一种有效的途径,MSC 是细胞治疗的良好候选物,这可能是治疗慢性肾脏病的一种有前途的方法。

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