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比较雷帕霉素和秋水仙碱治疗对腹膜透析大鼠腹膜纤维化发展的影响。

Comparison of sirolimus and colchicine treatment on the development of peritoneal fibrozis in rats having peritoneal dialysis.

机构信息

Deptartment of General Surgery, Trakya University Faculty of Medicine, Edirne, Turkey.

Deparment of Emergency Medicine, Trakya University Faculty of Medicine, Edirne, Turkey.

出版信息

Balkan Med J. 2015 Jan;32(1):101-6. doi: 10.5152/balkanmedj.2015.15183. Epub 2015 Jan 1.

Abstract

BACKGROUND

Continuous ambulatory peritoneal dialysis is a successful treatment modality for patients with end-stage renal disease. Peritoneal fibrosis (PF) is the most critical complication of long-term peritoneal dialysis (PD).

AIMS

In our study, we aimed to compare the effects of colchicine and sirolimus on PF induced by hypertonic peritoneal dialysis solutions in rats.

STUDY DESIGN

Animal experiment.

METHODS

Twenty-four rats were randomly divided into three groups. The control group received an intraperitoneal injection (ip) of saline. The sirolimus group received the PD solution, plus 1.0 mg/kg/day Rapamune®. The colchicine group received the PD solution ip plus 1.0 mg/kg/day of colchicine. Blood samples were taken to measure the serum levels of VEGF, TGF-β, and TNF-α. Peritoneal tissue samples were taken for histopathological evaluation.

RESULTS

TGF-β and TNF-α values in the sirolimus group were found to be statistically significantly lower than in the control and colchicine groups, but the differences between the control and colchicine groups were not statistically significant. No statistically significant differences were found between the groups regarding the VEGF values. Vascular neogenesis and peritoneal thickness were compared; the values in the sirolimus group were statistically reduced compared to the values in the control group. Mild fibrosis developed in 75% of all animals in the sirolimus group; there was no moderate or severe fibrosis observed. Fibrosis developed to varying degrees in 100% of the animals in the control and colchicine groups.

CONCLUSION

The present study demonstrates that sirolimus might be beneficial for preventing or delaying the progression of PF and neoangiogenesis. These alterations in the peritoneal membrane may be connected with reduced TNF-α and TGF-β levels.

摘要

背景

持续性不卧床腹膜透析是治疗终末期肾病患者的一种成功治疗方式。腹膜纤维化(PF)是长期腹膜透析(PD)最关键的并发症。

目的

在我们的研究中,我们旨在比较秋水仙碱和西罗莫司对高渗腹膜透析液诱导的大鼠 PF 的影响。

研究设计

动物实验。

方法

24 只大鼠随机分为三组。对照组接受腹腔内注射生理盐水。西罗莫司组接受 PD 溶液,加 1.0mg/kg/天 Rapamune®。秋水仙碱组接受 PD 溶液腹腔内注射加 1.0mg/kg/天秋水仙碱。采集血样测量血清 VEGF、TGF-β 和 TNF-α 水平。取腹膜组织样本进行组织病理学评估。

结果

西罗莫司组 TGF-β 和 TNF-α 值明显低于对照组和秋水仙碱组,但对照组和秋水仙碱组之间的差异无统计学意义。三组间 VEGF 值无统计学差异。比较血管新生和腹膜厚度,西罗莫司组值明显低于对照组。西罗莫司组所有动物的纤维化程度均为轻度,无中度或重度纤维化。对照组和秋水仙碱组的动物均有不同程度的纤维化。

结论

本研究表明,西罗莫司可能有益于预防或延缓 PF 和新生血管形成的进展。这些腹膜膜的改变可能与 TNF-α 和 TGF-β 水平降低有关。

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