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姜黄素脂质体递送至肾小管上皮细胞和抗原提呈细胞减轻肾缺血再灌注损伤。

Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

机构信息

Transplant Immunology Laboratory, Hanson Institute, Adelaide, SA, Australia.

出版信息

Br J Pharmacol. 2012 May;166(1):194-209. doi: 10.1111/j.1476-5381.2011.01590.x.

Abstract

BACKGROUND AND PURPOSE

Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway.

EXPERIMENTAL APPROACH

We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting.

KEY RESULTS

Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein.

CONCLUSIONS AND IMPLICATIONS

Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury.

摘要

背景与目的

肾缺血再灌注(IR)损伤是肾移植不可避免的后果,导致严重的移植物损伤,增加排斥反应的风险,并导致移植物预后不良。肾损伤是由细胞因子和趋化因子的合成、炎症和氧化应激介导的,这些都是 NF-κB 通路激活的结果。

实验方法

我们利用 NF-κB 通路的一种强效抑制剂姜黄素的脂质体包封,将其靶向递送至肾小管上皮细胞和抗原呈递细胞。在 C57/B6 小鼠双侧肾缺血前给予含有姜黄素的脂质体,然后再进行再灌注。再灌注后 4 和 24 小时,通过血浆尿素和肌酐水平评估肾功能。用组织学、免疫染色和 TUNEL 检测评估肾组织 NF-κB 活性和氧化应激以及细胞凋亡。通过 RT-PCR 和 Western blot 检测细胞因子和趋化因子。

主要结果

脂质体姜黄素显著改善了血清肌酐,减轻了组织学损伤和细胞凋亡,降低了 Toll 样受体-4、热休克蛋白-70 和 TNF-α 的 mRNA 表达。脂质体姜黄素还减少了中性粒细胞浸润和炎症趋化因子的表达。姜黄素脂质体减少了细胞内超氧阴离子的产生,增加了超氧化物歧化酶的水平,降低了诱导型一氧化氮合酶的 mRNA 表达和 3-硝基酪氨酸染色,这与减少硝化应激和抑制肾小管硫氧还蛋白相互作用蛋白的 mRNA 和蛋白表达一致。姜黄素的这些作用是通过抑制 NF-κB、MAPK 和磷酸化 S6 核糖体蛋白来介导的。

结论和意义

姜黄素的脂质体递送促进了这种无毒化合物的有效、靶向递送,在肾 IR 损伤后通过抗炎和多种抗氧化机制提供了细胞保护作用。

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本文引用的文献

1
Curcumin induces maturation-arrested dendritic cells that expand regulatory T cells in vitro and in vivo.
Clin Exp Immunol. 2010 Dec;162(3):460-73. doi: 10.1111/j.1365-2249.2010.04232.x.
2
Curcumin targeted signaling pathways: basis for anti-photoaging and anti-carcinogenic therapy.
Int J Dermatol. 2010 Jun;49(6):608-22. doi: 10.1111/j.1365-4632.2010.04468.x.
3
Anti-inflammatory treatment strategies for ischemia/reperfusion injury in transplantation.
J Inflamm (Lond). 2010 May 28;7:27. doi: 10.1186/1476-9255-7-27.
6
Antigen-specific suppression of inflammatory arthritis using liposomes.
J Immunol. 2009 Mar 15;182(6):3556-65. doi: 10.4049/jimmunol.0802972.
7
Expression, localization, and function of the thioredoxin system in diabetic nephropathy.
J Am Soc Nephrol. 2009 Apr;20(4):730-41. doi: 10.1681/ASN.2008020142. Epub 2009 Feb 11.
9
The A20 gene protects kidneys from ischaemia/reperfusion injury by suppressing pro-inflammatory activation.
J Mol Med (Berl). 2008 Dec;86(12):1329-39. doi: 10.1007/s00109-008-0405-4. Epub 2008 Sep 24.
10
Roles of chemokines in renal ischemia/reperfusion injury.
Front Biosci. 2008 May 1;13:4021-8. doi: 10.2741/2990.

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