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替米沙坦单独或与依那西普联合使用可改善类风湿关节炎相关贫血:可能具有抗炎和肾保护作用。

Telmisartan alone or in combination with etanercept improves anemia associated with rheumatoid arthritis in rats: a possible role of anti-inflammatory and reno-protective effects.

机构信息

Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Abbasia, Cairo, Egypt.

出版信息

Pharmacol Rep. 2020 Apr;72(2):379-388. doi: 10.1007/s43440-019-00033-w. Epub 2020 Jan 8.

Abstract

BACKGROUND

There are conflicting data regarding angiotensin receptor blockers (ARBs) induced anemia and its beneficial anti-inflammatory effect in rheumatoid arthritis. The aim of the present study was to investigate the effect of telmisartan administration either alone or in combination with etanercept on anemia of chronic inflammatory diseases in a model of rheumatoid arthritis in rats.

METHODS

Rheumatoid arthritis (RA) was induced by Freund's Complete Adjuvant (FCA; 1 mg/0.1 ml paraffin oil), injected subcutaneously on days 0, 30 and 40. Rats with RA received dimethyl sulfoxide (DMSO), etanercept (0.3 mg/kg 3 times/week; sc), telmisartan (1.5 mg/kg/day; orally) or combination of etanercept and telmisartan. Arthritis parameters (footpad circumference change and paw volume change), erythrocyte indices (hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin level changes), iron profile (serum iron and serum ferritin), serum levels of erythropoietin (EPO), hepcidin, tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 were evaluated, along with measuring serum urea and creatinine levels.

RESULTS

All treated groups showed improvement of the measured parameters in comparison to RA-control subgroup. Telmisartan either alone or in combination with etanercept significantly improved arthritis and erythrocyte indices. Telmisartan showed significant increase in EPO and decrease in hepcidin compared to etanercept. Combination group showed significant improvement in serum iron, ferritin, EPO, hepcidin, TNF-α, IL-6, urea and creatinine, compared to etanercept. Telmisartan either alone or in combination, but not etanercept alone, significantly decreased creatinine level.

CONCLUSION

Telmisartan improved anemia and arthritis parameters and showed anti-inflammatory and reno-protective effects, in a rat model of rheumatoid arthritis.

摘要

背景

血管紧张素受体阻滞剂(ARB)引起贫血及其在类风湿关节炎中的有益抗炎作用存在相互矛盾的数据。本研究旨在探讨替米沙坦单独或联合依那西普给药对类风湿关节炎大鼠模型中慢性炎症性疾病贫血的影响。

方法

弗氏完全佐剂(FCA;1mg/0.1ml 石蜡油)皮下注射诱导类风湿关节炎(RA),分别于第 0、30 和 40 天注射。RA 大鼠给予二甲基亚砜(DMSO)、依那西普(0.3mg/kg,每周 3 次,皮下注射)、替米沙坦(1.5mg/kg/天,口服)或依那西普和替米沙坦联合用药。评估关节炎参数(足垫周长变化和足爪体积变化)、红细胞指数(血红蛋白、平均红细胞体积和平均红细胞血红蛋白水平变化)、铁谱(血清铁和血清铁蛋白)、血清红细胞生成素(EPO)、hepcidin、肿瘤坏死因子-α(TNF-α)和白细胞介素(IL)-6 水平,并测量血清尿素和肌酐水平。

结果

与 RA 对照组相比,所有治疗组的测量参数均有所改善。替米沙坦单独或联合依那西普均可显著改善关节炎和红细胞指数。与依那西普相比,替米沙坦可显著增加 EPO,降低 hepcidin。与依那西普相比,联合组血清铁、铁蛋白、EPO、hepcidin、TNF-α、IL-6、尿素和肌酐均有显著改善。替米沙坦单独或联合使用,而依那西普单独使用,均可显著降低肌酐水平。

结论

替米沙坦可改善贫血和关节炎参数,并在类风湿关节炎大鼠模型中表现出抗炎和肾保护作用。

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