秋水仙碱对包裹性腹膜硬化进展和消退的影响。

The effects of colchicine on the progression and regression of encapsulating peritoneal sclerosis.

作者信息

Bozkurt Devrim, Bicak Selahattin, Sipahi Savas, Taskin Huseyin, Hur Ender, Ertilav Muhittin, Sen Sait, Duman Soner

机构信息

Department of Nephrology, Ege University, Izmir, Turkey.

出版信息

Perit Dial Int. 2008 Nov;28 Suppl 5:S53-7.

PMID:19008543

Abstract

BACKGROUND

Encapsulating peritoneal sclerosis (EPS) is an infrequent but extremely serious complication of long-term peritoneal dialysis. Fibrosis of the submesothelial compact zone and neoangiogenesis underlie the pathophysiology of EPS. Colchicine is a well-known anti-inflammatory and antifibrotic agent that has been used for some fibrosing clinical states, such as liver fibrosis.

OBJECTIVE

To determine the antifibrotic and anti-inflammatory effects of colchicine in an EPS rat model in both progression (P) and regression (R).

METHODS

48 nonuremic albino Wistar rats were divided into 5 groups: control group, 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group, IP injection of 2 mL/200 g chlorhexidine gluconate (CG) (0.1%) and ethanol (15%) dissolved in saline, daily for 3 weeks; resting group, CG (0 - 3 weeks) + peritoneal resting (4 - 6 weeks); C-R group, CG (0 - 3 weeks) + 1 mg/L colchicine (4 - 6 weeks); C-P group, CG (0 - 3 weeks) + 1 mg/L colchicine in drinking water (0 - 3 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% peritoneal dialysis solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume, and morphological changes of parietal peritoneum were examined.

RESULT

Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased ultrafiltration volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Resting had some beneficial effects on peritoneal derangements; however, once the peritoneum had been stimulated, resting alone was not enough to reverse these pathological changes. Colchicine had more pronounced effects on membrane integrity via decreased inflammation, cell infiltration, and vascularity compared to the resting group.

CONCLUSION

We suggest that colchicine may have therapeutic value in the management of EPS.

摘要

背景

包裹性腹膜硬化（EPS）是长期腹膜透析中一种罕见但极其严重的并发症。间皮下致密层纤维化和新生血管形成是EPS病理生理学的基础。秋水仙碱是一种著名的抗炎和抗纤维化药物，已用于一些纤维化临床状态，如肝纤维化。

目的

确定秋水仙碱在EPS大鼠模型进展期（P）和消退期（R）的抗纤维化和抗炎作用。

方法

48只非尿毒症白化Wistar大鼠分为5组：对照组，每天腹腔内注射2 mL等渗盐水，共3周；CG组，每天腹腔内注射2 mL/200 g葡萄糖酸氯己定（CG）（0.1%）和溶解于盐水中的乙醇（15%），共3周；静止组，CG处理（0 - 3周）+腹膜静止（4 - 6周）；C-R组，CG处理（0 - 3周）+ 1 mg/L秋水仙碱（4 - 6周）；C-P组，CG处理（0 - 3周）+饮用水中1 mg/L秋水仙碱（0 - 3周）。最后，用25 mL 3.86%腹膜透析液进行1小时腹膜平衡试验。检测尿素的透析液与血浆比值（D/P尿素）、透析液白细胞计数、超滤量和壁层腹膜的形态学变化。

结果

CG处理3周导致腹膜转运改变（D/P尿素增加，超滤量减少；p < 0.05）和形态学改变（炎症、新生血管形成、纤维化和腹膜厚度增加；p < 0.05）。静止对腹膜紊乱有一些有益作用；然而，一旦腹膜受到刺激，仅靠静止不足以逆转这些病理变化。与静止组相比，秋水仙碱通过减轻炎症、细胞浸润和血管形成对膜完整性有更显著的作用。