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胎球蛋白-A在猪血液透析移植物失功模型早期静脉狭窄形成中的表达

Fetuin-A expression in early venous stenosis formation in a porcine model of hemodialysis graft failure.

作者信息

Misra Sanjay, Fu Alex A, Anderson Jill L, Glockner James F, McKusick Michael A, Bjarnason Haraldur, Woodrum David A, Mukhopadhyay Debabrata

机构信息

Department of Radiology, Mayo Clinic College of Medicine, 200 First Street Southwest, Alfred 6460, Rochester, MN 55905, USA.

出版信息

J Vasc Interv Radiol. 2008 Oct;19(10):1477-82. doi: 10.1016/j.jvir.2008.06.007. Epub 2008 Aug 9.

DOI:10.1016/j.jvir.2008.06.007
PMID:18693047
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2583174/
Abstract

PURPOSE

Because fetuin-A is a cytokine with multifunctional effects on vascular smooth muscle cells and fibroblasts, the authors examined the course of its expression in early venous stenosis formation in a porcine model of chronic renal insufficiency with polytetrafluoroethylene (PTFE) arteriovenous (AV) hemodialysis grafts.

MATERIALS AND METHODS

Pigs had chronic renal insufficiency created by complete embolization of the left kidney and partial embolization of the right kidney. Twenty-eight days later, PTFE AV grafts were placed from the carotid artery to the ipsilateral jugular vein, and the animals were euthanized 3 days (n = 4), 7 days (n = 4), or 14 days (n = 4) later. Expression of fetuin-A was determined by Western blot analysis of the venous stenosis, control veins, and plasma. Immunohistochemical analysis of the venous stenosis and control vein was performed. Blood urea nitrogen (BUN) and creatinine were measured before embolization and at the time of graft placement.

RESULTS

The mean BUN and creatinine levels at graft placement were significantly higher than before embolization (P < .05). Severe venous neointimal hyperplasia occurred by day 14 and was characterized by primarily alpha-smooth muscle actin-positive cells. By day 14, fetuin-A levels had increased significantly (P < .05) at the venous stenosis compared with control veins and in the serum compared with measurements before embolization.

CONCLUSIONS

Significantly increased expression of fetuin-A was observed in early venous stenosis by day 14 and in serum compared with baseline measurements. Understanding the role of fetuin-A in venous neointimal hyperplasia could help in improving outcomes in patients undergoing hemodialysis.

摘要

目的

胎球蛋白-A是一种对血管平滑肌细胞和成纤维细胞具有多种功能作用的细胞因子,作者在一个使用聚四氟乙烯(PTFE)动静脉(AV)血液透析移植物的慢性肾功能不全猪模型中,研究了其在早期静脉狭窄形成过程中的表达情况。

材料与方法

通过完全栓塞左肾和部分栓塞右肾使猪产生慢性肾功能不全。28天后,将PTFE AV移植物从颈动脉放置到同侧颈静脉,并在3天(n = 4)、7天(n = 4)或14天(n = 4)后对动物实施安乐死。通过对静脉狭窄处、对照静脉和血浆进行蛋白质免疫印迹分析来测定胎球蛋白-A的表达。对静脉狭窄处和对照静脉进行免疫组织化学分析。在栓塞前和移植物放置时测量血尿素氮(BUN)和肌酐。

结果

移植物放置时的平均BUN和肌酐水平显著高于栓塞前(P <.05)。到第14天时出现严重的静脉内膜增生,其主要特征是α平滑肌肌动蛋白阳性细胞。到第14天时,与对照静脉相比,静脉狭窄处的胎球蛋白-A水平显著升高(P <.05),与栓塞前测量值相比,血清中的胎球蛋白-A水平也显著升高。

结论

与基线测量值相比,在第14天的早期静脉狭窄处和血清中观察到胎球蛋白-A的表达显著增加。了解胎球蛋白-A在静脉内膜增生中的作用可能有助于改善血液透析患者的治疗效果。

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