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枸橼酸西地那非可增强将后肾异体移植到未免疫抑制宿主后的肾脏器官发生。

Sildenafil Citrate Enhances Renal Organogenesis Following Metanephroi Allotransplantation into Non-Immunosuppressed Hosts.

作者信息

Garcia-Dominguez Ximo, Vera-Donoso César D, Lopez-Moncholi Eric, Moreno-Manzano Victoria, Vicente José S, Marco-Jiménez Francisco

机构信息

Laboratory of Biotechnology of Reproduction, Institute for Animal Science and Technology (ICTA), Universitat Politècnica de València, 46022 Valencia, Spain.

Servicio de Urología, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain.

出版信息

J Clin Med. 2022 May 29;11(11):3068. doi: 10.3390/jcm11113068.

Abstract

In order to harness the potential of metanephroi allotransplantation to the generation of a functional kidney graft on demand, we must achieve further growth post-transplantation. Sildenafil citrate (SC) is widely known as a useful inductor of angiogenesis, offering renoprotective properties due to its anti-inflammatory, antifibrotic, and antiapoptotic effects. Here, we performed a laparoscopic metanephroi allotransplantation after embedding sildenafil citrate into the retroperitoneal fat of non-immunosuppressed adult rabbit hosts. Histology and histomorphometry were used to examine the morphofunctional changes in new kidneys 21 days post-transplantation. Immunofluorescence of E-cadherin and renin and erythropoietin gene expression were used to assess the tubule integrity and endocrine functionality. After the metanephroi were embedded in a 10 µM SC solution, the new kidneys' weights become increased significantly. The E-cadherin expression together with the renin and erythropoietin gene expression revealed its functionality, while histological mature glomeruli and hydronephrosis proved the new kidneys' excretory function. Thus, we have described a procedure through the use of SC that improves the outcomes after a metanephroi transplantation. This study gives hope to a pathway that could offer a handsome opportunity to overcome the kidney shortage.

摘要

为了充分发挥后肾异体移植的潜力,按需生成功能正常的肾移植器官,我们必须在移植后实现进一步生长。枸橼酸西地那非(SC)作为一种有用的血管生成诱导剂广为人知,因其抗炎、抗纤维化和抗凋亡作用而具有肾脏保护特性。在此,我们将枸橼酸西地那非嵌入未免疫抑制的成年兔宿主的腹膜后脂肪中,进行了腹腔镜下后肾异体移植。移植后21天,采用组织学和组织形态计量学方法检查新肾的形态功能变化。采用E-钙黏蛋白免疫荧光以及肾素和促红细胞生成素基因表达评估肾小管完整性和内分泌功能。将后肾嵌入10µM的SC溶液中后,新肾重量显著增加。E-钙黏蛋白表达以及肾素和促红细胞生成素基因表达显示了其功能,而组织学上成熟的肾小球和肾积水证明了新肾的排泄功能。因此,我们描述了一种通过使用SC来改善后肾移植术后结果的方法。这项研究为克服肾脏短缺提供了一个绝佳机会的途径带来了希望。

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