AST-120 可改善慢性肾脏病大鼠肾脏中的上皮间质转化和间质纤维化。

AST-120 ameliorates epithelial-to-mesenchymal transition and interstitial fibrosis in the kidneys of chronic kidney disease rats.

机构信息

Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.

出版信息

J Ren Nutr. 2012 Jan;22(1):176-80. doi: 10.1053/j.jrn.2011.10.015.

DOI:10.1053/j.jrn.2011.10.015

PMID:22200438

Abstract

OBJECTIVE

Indoxyl sulfate (IS), a uremic toxin, is a risk factor for progression of chronic kidney disease (CKD). AST-120 reduces serum IS and delays the progression of CKD. This study aimed to examine whether AST-120 inhibits epithelial-to-mesenchymal transition (EMT) in the kidneys of CKD rats.

METHODS

CKD rats were produced by 5/6 nephrectomy and were divided into 2 groups: (1) CKD rats and (2) AST-120-treated CKD rats at a dosage of 4 g/kg body weight/day. After 10 weeks, their kidneys were excised for histological and immunohistochemical analysis. EMT was evaluated by immunohistochemistry of zonula occludens (ZO-1), an epithelial marker, and alpha-smooth muscle actin (α-SMA), a mesenchymal marker. Interstitial fibrosis was evaluated by Masson's trichrome staining.

RESULTS

CKD rats showed reduced expression of ZO-1 and enhanced expression of α-SMA as compared with normal rats. Administration of AST-120 to CKD rats increased expression of ZO-1 and decreased expression of α-SMA as compared with CKD rats. Further, CKD rats showed enhanced extent of interstitial fibrosis as compared with normal rats, and administration of AST-120 to CKD rats ameliorated interstitial fibrosis. CKD rats showed increased serum level of IS as compared with normal rats, whereas administration of AST-120 to CKD rats decreased both serum and urine levels of IS.

CONCLUSION

We conclude that AST-120 ameliorated EMT and interstitial fibrosis in the kidneys of CKD rats, probably by alleviating IS overload on the kidneys.

摘要

目的

硫酸吲哚酚（IS）是一种尿毒症毒素，是慢性肾脏病（CKD）进展的危险因素。AST-120 可降低血清 IS 水平并延缓 CKD 的进展。本研究旨在探讨 AST-120 是否能抑制 CKD 大鼠肾脏中的上皮间质转化（EMT）。

方法

通过 5/6 肾切除术制备 CKD 大鼠，并将其分为 2 组：（1）CKD 大鼠组和（2）AST-120 治疗的 CKD 大鼠组（剂量为 4 g/kg 体重/天）。10 周后，切除其肾脏进行组织学和免疫组织化学分析。通过紧密连接蛋白（ZO-1），一种上皮标志物，和α-平滑肌肌动蛋白（α-SMA），一种间充质标志物的免疫组化评估 EMT。通过 Masson 三色染色评估间质纤维化。

结果

与正常大鼠相比，CKD 大鼠的 ZO-1 表达减少，α-SMA 表达增强。与 CKD 大鼠相比，AST-120 治疗的 CKD 大鼠的 ZO-1 表达增加，α-SMA 表达减少。此外，与正常大鼠相比，CKD 大鼠的间质纤维化程度增加，AST-120 治疗的 CKD 大鼠的间质纤维化程度减轻。与正常大鼠相比，CKD 大鼠的血清 IS 水平升高，而 AST-120 治疗的 CKD 大鼠的血清和尿液 IS 水平均降低。