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负载姜黄素的纳米颗粒可预防横纹肌溶解诱导的急性肾损伤。

Curcumin-Loaded Nanoparticles Protect Against Rhabdomyolysis-Induced Acute Kidney Injury.

作者信息

Chen Xiaoling, Sun Jian, Li Hailun, Wang Hongwu, Lin Yongtao, Hu Yu, Zheng Donghui

机构信息

Department of Nephrology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai´an, China.

DDepartment of Anesthesiology, Huai´an Maternal and Child Health Hospital, Huai'an, China.

出版信息

Cell Physiol Biochem. 2017;43(5):2143-2154. doi: 10.1159/000484233. Epub 2017 Oct 24.

Abstract

BACKGROUND/AIMS: Rhabdomyolysis (RM) is a potentially life-threatening condition that results from the breakdown of muscle and consequent release of toxic compounds into circulation. The most common and severe complication of RM is acute kidney injury (AKI). This study aimed to evaluate the efficacy and mechanisms of action of curcumin-loaded nanoparticles (Cur-NP) for treatment of RM-induced AKI.

METHODS

Curcumin-NP was synthesized using the nanocarrier distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) to achieve a prolonged and constant drug release profile compared with the curcumin-free group. The anti-AKI effects of Curcumin-NP were examined both in vitro (myoglobin-treated renal tubular epithelial HK-2 cells) and in vivo (glycerol-induced AKI model).

RESULTS

Our results indicated that Curcumin-NP reversed oxidative stress, growth inhibition and cell apoptosis accompanied with down-regulation of apoptotic markers Caspase-3 and GRP-78 in vitro. In vivo studies revealed enhanced AKI treatment efficacy with Curcumin-NP as characterized by reduced serum creatine phosphokinase (CPK), creatinine (Cr) and urea and less severe histological damage in renal tubules. In addition, kidney tissues from Curcumin-NP-treated AKI rats exhibited reduced oxidative stress, apoptosis, and cleaved Capase-3 and GRP-78 expression.

CONCLUSION

Our results suggest that nanoparticle-loaded curcumin enhances treatment efficacy for RM-induced AKI both in vitro and in vivo.

摘要

背景/目的:横纹肌溶解症(RM)是一种潜在的危及生命的病症,由肌肉分解以及随之而来的有毒化合物释放进入循环系统所致。RM最常见且最严重的并发症是急性肾损伤(AKI)。本研究旨在评估载姜黄素纳米颗粒(Cur-NP)治疗RM诱导的AKI的疗效及作用机制。

方法

使用纳米载体二硬脂酰磷脂酰乙醇胺-聚乙二醇(DSPE-PEG)合成姜黄素纳米颗粒,以实现与无姜黄素组相比更长时间且持续的药物释放曲线。在体外(经肌红蛋白处理的肾小管上皮HK-2细胞)和体内(甘油诱导的AKI模型)检测姜黄素纳米颗粒的抗AKI作用。

结果

我们的结果表明,姜黄素纳米颗粒在体外逆转了氧化应激、生长抑制和细胞凋亡,并伴随凋亡标志物半胱天冬酶-3(Caspase-3)和葡萄糖调节蛋白78(GRP-78)的下调。体内研究显示,姜黄素纳米颗粒增强了AKI的治疗效果,表现为血清肌酸磷酸激酶(CPK)、肌酐(Cr)和尿素降低,肾小管组织学损伤较轻。此外,经姜黄素纳米颗粒治疗的AKI大鼠的肾组织氧化应激、细胞凋亡以及裂解的半胱天冬酶-3和GRP-78表达均降低。

结论

我们的结果表明,载纳米颗粒的姜黄素在体外和体内均增强了对RM诱导的AKI的治疗效果。

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