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银杏内酯 B 可抑制 TNFα 处理下人脐静脉内皮细胞在层流剪切应力下的血小板和单核细胞黏附。

Ginkgolide B inhibits platelet and monocyte adhesion in TNFα-treated HUVECs under laminar shear stress.

机构信息

MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.

Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

出版信息

BMC Complement Altern Med. 2018 Jul 20;18(1):220. doi: 10.1186/s12906-018-2284-8.

DOI:10.1186/s12906-018-2284-8
PMID:30029641
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6053749/
Abstract

BACKGROUND

Endothelial cells are sensitive to changes in both blood components and mechanical stimuli. Endothelial cells may undergo phenotypic changes, such as changes in adhesion protein expression, under different shear stress conditions. Such changes may impact platelet and monocyte adhesion to endothelial cells. This phenomenon is linked to chronic vascular inflammation and the development of atherosclerosis. In the present study, we investigated the effects of ginkgolide B on platelet and monocyte adhesion to human umbilical vein endothelial cells (HUVECs) under different conditions of laminar shear stress.

METHODS

Platelet and monocyte adhesion to endothelial cells was determined by the Bioflux 1000. HUVECs were incubated with ginkgolide B or aspirin for 12 h, and then TNFα was added for 2 h to induce the inflammatory response under conditions of 1 and 9 dyn/cm laminar shear stress. The protein expression was analyzed by Western blot.

RESULTS

The number of platelets that adhered was greater under conditions of 1 dyn/cm than under conditions of 9 dyn/cm of laminar shear stress (74.8 ± 19.2 and 59.5 ± 15.1, respectively). Ginkgolide B reduced the tumor necrosis factor α (TNFα)-induced increase in platelet and monocyte adhesion to HUVECs at 1 and 9 dyn/cm of laminar shear stress. In TNFα-treated HUVECs, the number of monocytes that adhered was greater under conditions of 1 dyn/cm of laminar shear stress compared with 9 dyn/cm (29.1 ± 4.9 and 22.7 ± 3.7, respectively). Ginkgolide B inhibited the TNFα-induced expression of vascular cell adhesion molecule-1(VCAM-1), VE-cadherin, and Cx43 in HUVECs at 1 and 9 dyn/cm. The expression of these proteins was not different between 1 and 9 dyn/cm.

CONCLUSIONS

Ginkgolide B suppressed platelet and monocyte adhesion under different conditions of laminar shear stress. Moreover, ginkgolide B reduced VCAM-1, VE-cadherin and Cx43 expression in TNFα-treated HUVECs under laminar shear stress. This suggested that ginkgolide B might shed light on the treatment of inflammation in atherosclerosis.

摘要

背景

内皮细胞对外周血成分和机械刺激的变化很敏感。在内皮细胞受到不同切变力的刺激时,内皮细胞可能会发生表型变化,例如黏附蛋白表达的改变。这种变化可能会影响血小板和单核细胞黏附在内皮细胞上。这种现象与慢性血管炎症和动脉粥样硬化的发展有关。在本研究中,我们研究了在不同层流切变应力条件下,银杏内酯 B 对人脐静脉内皮细胞(HUVEC)上血小板和单核细胞黏附的影响。

方法

通过 Bioflux 1000 检测血小板和单核细胞黏附在内皮细胞上的情况。将 HUVEC 用银杏内酯 B 或阿司匹林孵育 12 小时,然后在 1 和 9 dyn/cm 层流切变应力条件下加入 TNFα 2 小时以诱导炎症反应。通过 Western blot 分析蛋白表达。

结果

在 1 dyn/cm 条件下黏附的血小板数量多于在 9 dyn/cm 条件下(分别为 74.8±19.2 和 59.5±15.1)。银杏内酯 B 减少了 TNFα 诱导的在 1 和 9 dyn/cm 层流切变应力下血小板和单核细胞黏附到 HUVEC 上的增加。在 TNFα 处理的 HUVEC 中,在 1 dyn/cm 层流切变应力条件下黏附的单核细胞数量多于在 9 dyn/cm 条件下(分别为 29.1±4.9 和 22.7±3.7)。银杏内酯 B 抑制了 TNFα 诱导的在 1 和 9 dyn/cm 层流切变应力下 HUVEC 中血管细胞黏附分子-1(VCAM-1)、VE-钙黏蛋白和 Cx43 的表达。在 1 和 9 dyn/cm 时,这些蛋白的表达没有差异。

结论

银杏内酯 B 抑制了不同层流切变应力条件下血小板和单核细胞的黏附。此外,银杏内酯 B 减少了 TNFα 处理的 HUVEC 在层流切变应力下 VCAM-1、VE-钙黏蛋白和 Cx43 的表达。这表明银杏内酯 B 可能为动脉粥样硬化炎症的治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ca6/6053749/0c9652f8c174/12906_2018_2284_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ca6/6053749/ff29cdeb7dc3/12906_2018_2284_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ca6/6053749/3c71cdafe67d/12906_2018_2284_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ca6/6053749/d4e7712ebf17/12906_2018_2284_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ca6/6053749/0c9652f8c174/12906_2018_2284_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ca6/6053749/ff29cdeb7dc3/12906_2018_2284_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ca6/6053749/3c71cdafe67d/12906_2018_2284_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ca6/6053749/d4e7712ebf17/12906_2018_2284_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ca6/6053749/0c9652f8c174/12906_2018_2284_Fig4_HTML.jpg

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