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左旋四氢巴马汀通过下调细胞间黏附分子-1和血管细胞黏附分子-1,抑制核因子-κB信号通路,从而抑制肿瘤坏死因子-α诱导的单核细胞-内皮细胞黏附。

L-tetrahydropalamatine inhibits tumor necrosis factor-α-induced monocyte-endothelial cell adhesion through downregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 involving suppression of nuclear factor-κ B signaling pathway.

作者信息

Yang Bin-rui, Yu Nan, Deng Yan-hui, Hoi Pui Man, Yang Bin, Liu Guang-yu, Cong Wei-hong, Lee Simon Ming-yuen

机构信息

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.

出版信息

Chin J Integr Med. 2015 May;21(5):361-8. doi: 10.1007/s11655-015-2165-7. Epub 2015 Mar 17.

Abstract

OBJECTIVE

To investigate whether I-tetrahydropalmatine (I-THP), an alkaloid mainly present in Corydalis family, could ameliorate early vascular inflammatory responses in atherosclerotic processes.

METHODS

Fluorescently labeled monocytes were co-incubated with human umbilical vein endothelial cells (HUVECs), which were pretreated with I-THP and then simulated with tumor necrosis factor (TNF)-α in absence of I-THP to determine if I-THP could reduce thecytokine-induced adhesion of monocytes to HUVECs. Then I-THP were further studied the underlying mechanisms through observing the transcriptional and translational level of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the nuclear translocation of nuclear factor (NF)-κ B in HUVECs.

RESULTS

L-THP could block TNF-α-induced adhesion of monocytes to HUVECs and could significantly inhibited the expression of ICAM-1 and VCAM-1 on cell surface by 31% and 36% at 30 μ mol/L. L-THP pretreatment could also markedly reduce transcriptional and translational level of VCAM-1 as well as mildly reduce the total protein and mRNA expression levels of ICAM-1. Furthermore, I-THP attenuated TNF-α-stimulated NF-κ B nuclear translocation.

CONCLUSION

These results provide evidences supporting that I-THP could be a promising compound in the prevention and treatment of the early vascular inflammatory reaction in atherosclerosis by inhibiting monocyte adhesion to vascular endothelial cell through downregulating ICAM-1 and VCAM-1 in vascular endothelial cell based on suppressing NF-κ B.

摘要

目的

研究主要存在于罂粟科植物中的生物碱左旋四氢巴马汀(I-THP)是否能改善动脉粥样硬化进程中的早期血管炎症反应。

方法

将荧光标记的单核细胞与人脐静脉内皮细胞(HUVECs)共同孵育,HUVECs先用I-THP预处理,然后在无I-THP的情况下用肿瘤坏死因子(TNF)-α模拟处理,以确定I-THP是否能减少细胞因子诱导的单核细胞与HUVECs的黏附。然后通过观察HUVECs中细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)的转录和翻译水平以及核因子(NF)-κB的核转位,进一步研究I-THP的潜在机制。

结果

L-THP可阻断TNF-α诱导的单核细胞与HUVECs的黏附,并能在30μmol/L时显著抑制细胞表面ICAM-1和VCAM-1的表达,分别降低31%和36%。L-THP预处理还可显著降低VCAM-1的转录和翻译水平,并轻度降低ICAM-1的总蛋白和mRNA表达水平。此外,I-THP减弱了TNF-α刺激的NF-κB核转位。

结论

这些结果提供了证据支持I-THP可能是一种有前途的化合物,通过基于抑制NF-κB下调血管内皮细胞中的ICAM-1和VCAM-1,抑制单核细胞与血管内皮细胞的黏附,从而在动脉粥样硬化早期血管炎症反应的预防和治疗中发挥作用。

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