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阿托伐他汀通过诱导血红素加氧酶-1（HO-1）的表达来抑制脂多糖（LPS）诱导的血管炎症，从而保护内皮细胞。

Atorvastatin inhibits Lipopolysaccharide (LPS)-induced vascular inflammation to protect endothelium by inducing Heme Oxygenase-1 (HO-1) expression.

机构信息

Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Lu Zhou, China.

Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Lu Zhou, China.

出版信息

PLoS One. 2024 Aug 15;19(8):e0308823. doi: 10.1371/journal.pone.0308823. eCollection 2024.

DOI:10.1371/journal.pone.0308823
PMID:39146322
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11326635/
Abstract

PURPOSE

This study aimed to explore the differential effects of varying doses of atorvastatin on antagonizing lipopolysaccharide (LPS)-induced endothelial inflammation based on heme oxygenase 1 (HO-1) expression.

METHOD

Vascular endothelial inflammatory injury was induced in 40 Sprague-Dawley rats by intraperitoneal injection of LPS. These rats were randomly divided into control, low-dose atorvastatin, high-dose atorvastatin, and HO-1 blocking groups. Seven days after treatment, all rats were sacrificed, and heart-derived peripheral blood was collected to measure the serum concentrations of bilirubin, alanine aminotransferase (ALT), total cholesterol, malondialdehyde, endothelial cell protein C receptor, endothelin-1, von Willebrand factor, and soluble thrombomodulin. Meanwhile, the number of circulating endothelial cells was determined using flow cytometry. Vascular tissues from descending aorta of rats from each group were extracted to detect the expression level of HO-1.

RESULTS

After different doses of atorvastatin intervention, the above inflammatory indices were decreased, and HO-1 expression and ALT concentration were increased in the atorvastatin-treated group of rats compared with the control group. These changes were more pronounced in the high-dose statin group (P < 0.05). Conversely, no significant decrease in the above inflammatory indices and no significant increase in HO-1 expression were observed in rats in the blocking group (P > 0.05).

CONCLUSION

For LPS-induced vascular inflammation, high-dose atorvastatin exerts potent anti-inflammatory and vascular endothelial protection effects by inducing HO-1 expression.

摘要

目的

本研究旨在探讨不同剂量阿托伐他汀通过血红素氧合酶 1（HO-1）表达拮抗脂多糖（LPS）诱导的内皮炎症的差异作用。

方法

通过腹腔注射 LPS 诱导 40 只 Sprague-Dawley 大鼠血管内皮炎症损伤。将这些大鼠随机分为对照组、低剂量阿托伐他汀组、高剂量阿托伐他汀组和 HO-1 阻断组。治疗 7 天后，处死所有大鼠，采集心脏来源的外周血，测量血清胆红素、丙氨酸转氨酶（ALT）、总胆固醇、丙二醛、内皮细胞蛋白 C 受体、内皮素-1、血管性血友病因子和可溶性血栓调节蛋白的浓度。同时，使用流式细胞术测定循环内皮细胞的数量。提取各组大鼠降主动脉血管组织，检测 HO-1 的表达水平。

结果

经不同剂量阿托伐他汀干预后，上述炎症指标降低，阿托伐他汀治疗组大鼠 HO-1 表达和 ALT 浓度升高，与对照组相比差异有统计学意义（P<0.05）。他汀高剂量组变化更为显著（P<0.05）。相反，阻断组大鼠上述炎症指标未见明显下降，HO-1 表达未见明显升高（P>0.05）。

结论

对于 LPS 诱导的血管炎症，高剂量阿托伐他汀通过诱导 HO-1 表达发挥强大的抗炎和血管内皮保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b947/11326635/00a719e63d9b/pone.0308823.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b947/11326635/fe90859c0c89/pone.0308823.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b947/11326635/2f47413b8f01/pone.0308823.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b947/11326635/72c3e30ee32d/pone.0308823.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b947/11326635/00a719e63d9b/pone.0308823.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b947/11326635/fe90859c0c89/pone.0308823.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b947/11326635/2f47413b8f01/pone.0308823.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b947/11326635/72c3e30ee32d/pone.0308823.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b947/11326635/00a719e63d9b/pone.0308823.g004.jpg

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