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可溶性 Tie2 融合蛋白可减少尿毒症大鼠腹膜血管生成。

Soluble Tie2 fusion protein decreases peritoneal angiogenesis in uremic rats.

机构信息

Department of Nephrology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, PR China.

出版信息

Mol Med Rep. 2013 Jul;8(1):267-71. doi: 10.3892/mmr.2013.1478. Epub 2013 May 16.

DOI:10.3892/mmr.2013.1478
PMID:23685484
Abstract

Angiogenesis is considered to be one of the most common mechanisms leading to ultrafiltration failure (UFF) in long-term peritoneal dialysis (PD) patients. The angiopoietin (Ang)/Tie system was found to play a role in the initiation of pathological neoangiogenesis and is also involved in peritoneal angiogenesis caused by peritoneal fluid. This aim of this study was to investigate the effects of the soluble Tie2 fusion protein (sTie2/Fc) on peritoneal angiogenesis in PD-treated uremic rats. The rats were divided into 6 groups: normal, sham surgery, uremic rats without PD, uremic PD-treated rats, uremic rats treated with PD and sTie2/Fc (0.25 µg/100 g) and uremic rats treated with PD and sTie2/Fc (0.5 µg/100 g). PD rats were treated once a day for 28 days prior to testing. Real-time polymerase chain reaction (RT-PCR) or tissue immunohistochemical staining was used to detect Ang-2 mRNA or protein expression in the peritoneal tissues of each group. The microvessel density (MVD) of the peritoneum was detected and quantified by immunohistochemical staining using the anti-CD34 antibody. Compared with the control group, Ang-2 mRNA and protein expression was significantly upregulated in the uremic and PD groups (P<0.05). MVD in the experimental group increased compared with the control group. sTie2/Fc treatment decreased the levels of Ang-2 mRNA and protein expression (P<0.05) in a dose-dependent manner and decreased PD-induced MVD in the peritoneum. In conclusion, angiogenesis of the peritoneum induced by PD was inhibited using sTie2/Fc in a uremic rat model.

摘要

血管生成被认为是导致长期腹膜透析(PD)患者超滤失败(UFF)的最常见机制之一。血管生成素(Ang)/Tie 系统被发现在病理性新生血管形成的启动中发挥作用,并且也参与了由腹膜液引起的腹膜血管生成。本研究旨在探讨可溶性 Tie2 融合蛋白(sTie2/Fc)对 PD 治疗尿毒症大鼠腹膜血管生成的影响。大鼠分为 6 组:正常组、假手术组、非 PD 尿毒症组、PD 尿毒症组、PD 和 sTie2/Fc(0.25μg/100g)治疗的尿毒症组和 PD 和 sTie2/Fc(0.5μg/100g)治疗的尿毒症组。PD 大鼠在测试前每天治疗一次,持续 28 天。实时聚合酶链反应(RT-PCR)或组织免疫组织化学染色用于检测各组腹膜组织中 Ang-2 mRNA 或蛋白表达。通过使用抗 CD34 抗体的免疫组织化学染色检测腹膜的微血管密度(MVD)并进行定量。与对照组相比,尿毒症组和 PD 组 Ang-2 mRNA 和蛋白表达明显上调(P<0.05)。实验组的 MVD 与对照组相比增加。sTie2/Fc 治疗呈剂量依赖性降低 Ang-2 mRNA 和蛋白表达水平(P<0.05),并降低 PD 诱导的腹膜 MVD。结论,在尿毒症大鼠模型中,sTie2/Fc 抑制 PD 诱导的腹膜血管生成。

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Possible role of IL-6 and TIE2 gene polymorphisms in predicting the initial high transport status in patients with peritoneal dialysis: an observational study.
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BMJ Open. 2016 Oct 26;6(10):e012967. doi: 10.1136/bmjopen-2016-012967.
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A review of rodent models of peritoneal dialysis and its complications.腹膜透析及其并发症的啮齿动物模型综述。
Int Urol Nephrol. 2015 Jan;47(1):209-15. doi: 10.1007/s11255-014-0829-4. Epub 2014 Nov 26.
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Increased endothelial inflammation, sTie-2 and arginase activity in umbilical cords obtained from gestational diabetic mothers.来自妊娠糖尿病母亲的脐带中内皮炎症、可溶性血管内皮生长因子受体-2(sTie-2)和精氨酸酶活性增加。
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