KLF4 在动脉粥样硬化性胸主动脉中的上调：在高脂血症兔模型中探索秋水仙碱类方案的保护作用。

KLF4 Upregulation in Atherosclerotic Thoracic Aortas: Exploring the Protective Effect of Colchicine-based Regimens in a Hyperlipidemic Rabbit Model.

机构信息

First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece; Laboratory of Experimental Surgery and Surgical Research "N.S. Christeas", National and Kapodistrian University of Athens, Athens, Greece.

Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation Academy of Athens, Athens, Greece.

出版信息

Ann Vasc Surg. 2022 Jan;78:328-335. doi: 10.1016/j.avsg.2021.04.040. Epub 2021 Jun 26.

DOI:10.1016/j.avsg.2021.04.040

PMID:34182114

Abstract

BACKGROUND

Inflammatory dysregulation of KLF4 is related to atheromatosis. In the present study, we explored the impact of colchicine-based regimens on the development of thoracic aortic atheromatosis and KLF4 expression.

METHODS

Twenty-eight New Zealand White rabbits were divided to 4 groups. The control group (n = 6) was fed standard chow, group A (n = 6) was fed chow enriched with 1% w/w cholesterol, group B (n = 8) was fed the same cholesterol-enriched diet plus 2 mg/kg body weight/day colchicine and 250 mg/kg body weight/day fenofibrate, while group C (n = 8) was also fed the same diet plus 2 mg/kg body weight/day colchicine and 15 mg/kg body weight/day N-acetylcysteine. After 7 weeks, all animals were euthanized, and their thoracic aortas were isolated. Atherosclerotic plaque area was estimated with morphometric analysis. KLF4 expression was quantified with quantitative RT-PCR.

RESULTS

Group A developed significantly more atherosclerosis compared to group B (MD: 13.67, 95% CI: 7.49-19.84) and C (MD: 20.29, 95% CI: 14.12-26.47). Colchicine with N-acetylcysteine resulted in more pronounced reduction in the extent of atherosclerotic plaques compared to colchicine/fibrate (MD: 6.62, 95% CI: 0.90-12.34). Group A exhibited significantly greater KLF4 expression compared to group B (MD: 4.94, 95% CI: 1.11-8.77) and C (MD: 9.94, 95% CI: 6.11-13.77). Combining colchicine with N-acetylcysteine instead of fenofibrate (MD: 5.00, 95% CI: 1.45-8.54) led to a more robust reduction in KLF4 expression.

CONCLUSIONS

In the present hyperlipidemic animal model, colchicine-based regimens curtailed de novo atherogenesis and KLF4 overexpression in thoracic aortas.

摘要

背景

KLF4 的炎症失调与动脉粥样硬化有关。本研究探讨了秋水仙碱为基础的方案对胸主动脉粥样硬化和 KLF4 表达的影响。

方法

28 只新西兰白兔分为 4 组。对照组（n=6）喂饲标准饲料，A 组（n=6）喂饲富含 1%w/w 胆固醇的饲料，B 组（n=8）喂饲相同的富含胆固醇饮食加 2mg/kg 体重/天秋水仙碱和 250mg/kg 体重/天非诺贝特，C 组（n=8）也喂饲相同的饮食加 2mg/kg 体重/天秋水仙碱和 15mg/kg 体重/天 N-乙酰半胱氨酸。7 周后，所有动物安乐死，取其胸主动脉。采用形态计量学分析估计动脉粥样硬化斑块面积。用定量 RT-PCR 定量 KLF4 表达。

结果

A 组与 B 组（MD：13.67，95%CI：7.49-19.84）和 C 组（MD：20.29，95%CI：14.12-26.47）相比，动脉粥样硬化明显增多。秋水仙碱联合 N-乙酰半胱氨酸比秋水仙碱/贝特（MD：6.62，95%CI：0.90-12.34）更显著减少粥样斑块的程度。A 组 KLF4 表达明显高于 B 组（MD：4.94，95%CI：1.11-8.77）和 C 组（MD：9.94，95%CI：6.11-13.77）。与联合非诺贝特相比，秋水仙碱联合 N-乙酰半胱氨酸（MD：5.00，95%CI：1.45-8.54）导致 KLF4 表达更显著降低。