匹伐他汀通过抑制脂多糖刺激的人脐静脉内皮细胞中 miR-155 的表达而上调 eNOS 的产生。

Pitavastatin up-regulates eNOS production by suppressing miR-155 expression in lipopolysaccharide-stimulated human umbilical vein endothelial cells.

机构信息

Department of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.

Synthetic Biology Remaking Engineering and Application Laboratory, Xinxiang, Henan, China.

出版信息

Cardiovasc Ther. 2017 Oct;35(5). doi: 10.1111/1755-5922.12282.

DOI:10.1111/1755-5922.12282

PMID:28664667

Abstract

AIM

Pitavastatin (Pit) has been proved to efficiently inhibit the onset and progression of atherosclerosis. However, the mechanism by which Pit exerts nonlipid-related effects, such as antiinflammatory actions, is not quite clear. Our study aimed at investigating the effect of Pit on the expression of endothelial NO synthase (eNOS) and miR-155 in LPS-stimulated HUVECs to reveal the antiinflammatory mechanism of pitavastatin.

METHODS

HUVECs were isolated from newborn umbilical cords and used in the experiments at passages 2-5. Cells were treated with LPS (0.05, 0.1, 1 μg/L) or LPS (0.1 μg/L)+Pit (0.01, 0.1, 1 μmol/L), untreated cells were used as control. For LPS+Pit induction, cells were firstly incubated with Pit for 1 hour before coincubation with LPS for 24 hours. eNOS mRNA and miR-155 were detected by RT-PCR, and Western blotting was used to detect protein expression of eNOS.

RESULTS

Treatment of HUVECs with LPS enhanced the expression of miR-155 and reduced the expression of eNOS in mRNA and protein level in a dose-dependent manner as revealed by RT-PCR and Western blotting, respectively. Pitavastatin ameliorated LPS-induced endothelial dysfunction through upregulation of eNOS expression and downregulation of miR-155 expression.

CONCLUSION

Pitavastatin increases eNOS expression and inhibits of LPS-induced miR-155 expression.

摘要

目的

匹伐他汀（Pit）已被证明能有效抑制动脉粥样硬化的发生和进展。然而，匹伐他汀发挥非脂质相关作用（如抗炎作用）的机制尚不清楚。本研究旨在探讨匹伐他汀对 LPS 刺激的 HUVECs 中内皮型一氧化氮合酶（eNOS）和 miR-155 表达的影响，以揭示匹伐他汀的抗炎机制。

方法

从新生儿脐带中分离出 HUVECs，并在第 2-5 代用于实验。用 LPS（0.05、0.1、1μg/L）或 LPS（0.1μg/L）+匹伐他汀（0.01、0.1、1μmol/L）处理细胞，未处理的细胞作为对照。对于 LPS+匹伐他汀诱导，细胞先用匹伐他汀孵育 1 小时，然后与 LPS 共孵育 24 小时。通过 RT-PCR 检测 eNOS mRNA，Western blot 检测 eNOS 蛋白表达，检测 miR-155 的表达。