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纳米螯合纳米粒子 RAc1 的抗痛觉过敏作用可通过持续炎症期间肝铁调素表达的调节来介导。

Anti-hyperalgesia effect of nanchelating based nano particle, RAc1, can be mediated via liver hepcidin expression modulation during persistent inflammation.

机构信息

Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Research and Development, SodourAhrarShargh Company, Tehran, Iran.

出版信息

Int Immunopharmacol. 2019 Apr;69:337-346. doi: 10.1016/j.intimp.2019.02.003. Epub 2019 Feb 15.

Abstract

OBJECTIVE

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder accompanied with hyperalgesia, edema and pain. At least 30% of the patients failed to respond to the available treatments and medications, which yet have a lot of serious adverse effects on patients. So, using novel technologies to produce more efficient medications is needed. According to the role of iron manipulation in inflammatory process, we have synthetized RAc1 nano particle, which contains zinc and has iron chelating property. In the present study, we evaluated RAc1 nano particle effects on hyperalgesia and liver hepcidin and serum IL-1β and TNF-α expression levels during acute and chronic phases of adjuvant-induced inflammation in male rats and compared its effects with Deferoxamine.

METHODS AND MATERIALS

Complete Freund's adjuvant (CFA)-induced arthritis was caused by single subcutaneous injection of CFA into the rat's hind paw on day zero. RAc1 with 100, 200 and 400 ng/kg doses and deferoxamin with doses of 200 mg/kg after diluting in vehicles were administered daily (i.p.) during the 21 days of the study after CFA injection. Hyperalgesia, Edema, liver hepcidin and serum IL-1β and TNF-α expression levels were assessed on days 0, 7, 14 and 21 of the study.

RESULTS

The results of this study indicated the role of RAc1 nano particle administration in reducing paw edema, thermal hyperalgesia, and liver hepcidin and serum IL-1β and TNF-α expression even in comparison with Deferoxamine during different phases of inflammation caused by CFA.

CONCLUSION

It seems that RAc1 nano particle exerts its immune modulatory effects by decreasing liver hepcidin expression and serum IL-1β and TNF-α levels.

摘要

目的

类风湿性关节炎(RA)是一种慢性系统性炎症性疾病,伴有痛觉过敏、水肿和疼痛。至少有 30%的患者对现有治疗和药物治疗没有反应,而这些药物对患者有很多严重的副作用。因此,需要使用新的技术来生产更有效的药物。根据铁调控在炎症过程中的作用,我们合成了含有锌且具有铁螯合特性的 Rac1 纳米颗粒。在本研究中,我们评估了 Rac1 纳米颗粒对佐剂诱导的炎症大鼠急性和慢性期痛觉过敏以及肝铁调素和血清 IL-1β 和 TNF-α表达水平的影响,并将其与地拉罗司进行了比较。

方法和材料

完全弗氏佐剂(CFA)诱导的关节炎通过在大鼠后爪的单个皮下注射 CFA 于第 0 天引起。在 CFA 注射后,用载体稀释后,以 100、200 和 400ng/kg 剂量的 Rac1 和 200mg/kg 剂量的地拉罗司每天(ip)给药,持续 21 天。在研究的第 0、7、14 和 21 天评估痛觉过敏、水肿、肝铁调素和血清 IL-1β 和 TNF-α表达水平。

结果

本研究结果表明,即使与地拉罗司相比,Rac1 纳米颗粒的给药在 CFA 引起的不同炎症阶段也能减少爪水肿、热痛觉过敏以及肝铁调素和血清 IL-1β 和 TNF-α的表达。

结论

Rac1 纳米颗粒似乎通过降低肝铁调素表达和血清 IL-1β 和 TNF-α水平来发挥其免疫调节作用。

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