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商业脂质乳剂对内皮细胞完整性和炎症激活的调节作用。

Modulation of endothelial cell integrity and inflammatory activation by commercial lipid emulsions.

作者信息

Harvey Kevin A, Xu Zhidong, Pavlina Thomas M, Zaloga Gary P, Siddiqui Rafat A

机构信息

Cellular Biochemistry Laboratory, Methodist Research Institute, Indiana University Health, 1800 N. Capitol Ave, E504D, Indianapolis, IN, 46202, USA.

Baxter Healthcare Corporation, Deerfield, IL, 60015, USA.

出版信息

Lipids Health Dis. 2015 Feb 18;14:9. doi: 10.1186/s12944-015-0005-6.

Abstract

BACKGROUND

Thrombosis and immune dysfunction are two important complications that result from the administration of parenteral nutrition. Endothelial cells within the vasculature are crucial components necessary for maintenance of normal coagulation and immune function.

METHODS

We compared the effects of three commercial lipid emulsions (LEs; Intralipid®, ClinOleic® [or Clinolipid®], and Omegaven®) differing in the levels of omega-6 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-9 monounsaturated fatty acids, and saturated fatty acids upon endothelial cell fatty acid composition using Gas chromatography, endothelial cell integrity by assessing measurement of apoptosis and necrosis using flow cytometry, endothelial cell inflammatory activation by assessing the induction of ICAM-1 by lipopolysaccharide [LPS]), and transcription factor activation (phosphorylation of NF-κB) using western blot analysis.

RESULTS

Gas chromatographic analysis confirmed cellular uptake of the fatty acids within the LEs; furthermore, these fatty acid changes reflected the composition of the oils and egg phosphatides used in the manufacturing of these emulsions. However, the kinetics of fatty acid uptake and processing differed between LEs. Fish oil LE negatively impacted cell viability by doubling the percentage of apoptotic and necrotic cell populations quantified by flow cytometry using Annexin V/Fluorescein and propidium iodide. The soybean oil LE did not alter cell viability, while the olive oil-predominate emulsion improved cell viability. All LEs were capable of suppressing LPS-induced ICAM-1 expression; however, the fish oil LE was more potent than the other emulsions. Fish oil LE supplementation of cells also suppressed LPS-induced phosphorylation of NF-κB, while the soybean oil and olive predominant LE had no effect upon NF-κB phosphorylation.

CONCLUSIONS

Lipid emulsions are readily incorporated and stored in the form of triacylglycerols. Soybean oil-based, olive oil-predominant and fish-oil based LEs differentially affected endothelial cell integrity. Importantly, these three LEs were capable of suppressing endothelial cell inflammatory response despite their fatty acid content.

摘要

背景

血栓形成和免疫功能障碍是肠外营养应用过程中出现的两种重要并发症。脉管系统内的内皮细胞是维持正常凝血和免疫功能所必需的关键组成部分。

方法

我们比较了三种市售脂质乳剂(LEs;英脱利匹特®、克列诺林®[或克列诺利匹德®]和奥米加文®)对内皮细胞脂肪酸组成的影响,这三种乳剂在ω-6多不饱和脂肪酸、ω-3多不饱和脂肪酸、ω-9单不饱和脂肪酸和饱和脂肪酸水平上存在差异,采用气相色谱法进行分析;通过流式细胞术评估细胞凋亡和坏死情况来检测内皮细胞完整性;通过评估脂多糖(LPS)诱导的细胞间黏附分子-1(ICAM-1)的表达来检测内皮细胞炎症激活情况;采用蛋白质印迹分析检测转录因子激活(核因子κB(NF-κB)的磷酸化)情况。

结果

气相色谱分析证实了内皮细胞对脂质乳剂中脂肪酸的摄取;此外,这些脂肪酸变化反映了用于制造这些乳剂的油类和卵磷脂的成分。然而,不同脂质乳剂的脂肪酸摄取和代谢动力学存在差异。鱼油脂质乳剂使通过膜联蛋白V/荧光素和碘化丙啶利用流式细胞术定量的凋亡和坏死细胞群体百分比增加一倍,从而对细胞活力产生负面影响。大豆油脂质乳剂未改变细胞活力,而以橄榄油为主的乳剂提高了细胞活力。所有脂质乳剂均能够抑制LPS诱导的ICAM-1表达;然而,鱼油脂质乳剂比其他乳剂更有效。用鱼油脂质乳剂处理细胞也能抑制LPS诱导的NF-κB磷酸化,而大豆油和以橄榄油为主的脂质乳剂对NF-κB磷酸化无影响。

结论

脂质乳剂易于以三酰甘油的形式被摄取和储存。以大豆油、橄榄油为主和以鱼油为基础的脂质乳剂对内皮细胞完整性有不同影响。重要的是,尽管这三种脂质乳剂的脂肪酸含量不同,但它们均能够抑制内皮细胞炎症反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18f1/4339234/4055a07b3631/12944_2015_5_Fig1_HTML.jpg

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