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蛋白酶体抑制剂对动脉粥样硬化大鼠模型中血管细胞黏附分子-1(VCAM-1)和细胞间黏附分子-1(ICAM-1)表达的影响

Effect of Proteasome Inhibitor on Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule-1 (ICAM-1) Expressions in Rat Model of Atherosclerosis.

作者信息

Ismawati Ismawati, Romus Ilhami, Mukhyarjon Mukhyarjon, Muthya Afra

机构信息

Department of Biochemistry, Faculty of medicine, Riau University, Pekanbaru, Indonesia.

Department of Pathology Anatomy, Faculty of medicine, Riau University, Pekanbaru, Indonesia.

出版信息

Rep Biochem Mol Biol. 2022 Jan;10(4):633-639. doi: 10.52547/rbmb.10.4.633.

Abstract

BACKGROUND

The effect of proteasome inhibitors on atherosclerosis is known to vary depending on the atherosclerosis stage. Previous studies have shown that the highest proteasome expression in atherosclerotic lesions is at the progression stage. Adhesion molecules play a role in the progression stage of atherosclerosis, but no studies have analyzed the effect of proteasome inhibitors on the expression of adhesion molecules at this stage.

METHODS

This experimental study aimed to analyze the effect of a proteasome inhibitor, namely bortezomib, on the vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule1 (ICAM-1) expressions in blood vessels of rat model of atherosclerosis at the progression stage. This study used 18 male Wistar rats divided into three groups, i.e. group I that is the control group given standard feed, group II induced by atherosclerosis, and group III induced by atherosclerosis and given bortezomib. Atherosclerosis induction was performed using vitamin D3 (700,000 IU/kg) orally by gastric intubation on the 1st day and atherogenic feed given for four days. Bortezomib 50 µg/kgBW/day was administered intra-peritoneally. The expression of VCAM-1 and ICAM-1 molecules was measured using immunohistochemistry and analyzed quantitatively using Adobe Photoshop software.

RESULTS

The statistical test showed differences in VCAM-1 expression between atherosclerosis + Bortezomib group and atherosclerosis group, but there were no differences in the expression of ICAM-1 and atherosclerotic lesions between the groups.

CONCLUSION

Administration of bortezomib 50μg/kg for four days in progressive atherosclerosis model rats can inhibit VCAM-1 expression, although it does not affect ICAM-1 expression and cannot inhibit atherosclerotic lesion formation.

摘要

背景

已知蛋白酶体抑制剂对动脉粥样硬化的影响因动脉粥样硬化阶段而异。先前的研究表明,动脉粥样硬化病变中蛋白酶体的最高表达处于进展阶段。黏附分子在动脉粥样硬化的进展阶段起作用,但尚无研究分析蛋白酶体抑制剂在此阶段对黏附分子表达的影响。

方法

本实验研究旨在分析蛋白酶体抑制剂硼替佐米对动脉粥样硬化进展期大鼠模型血管中血管细胞黏附分子-1(VCAM-1)和细胞间黏附分子1(ICAM-1)表达的影响。本研究使用18只雄性Wistar大鼠,分为三组,即I组为给予标准饲料的对照组,II组为动脉粥样硬化诱导组,III组为动脉粥样硬化诱导并给予硼替佐米组。在第1天通过胃管口服维生素D3(700,000 IU/kg)进行动脉粥样硬化诱导,并给予致动脉粥样硬化饲料四天。以50 μg/kg体重/天的剂量腹腔注射硼替佐米。使用免疫组织化学法测量VCAM-1和ICAM-1分子的表达,并使用Adobe Photoshop软件进行定量分析。

结果

统计学检验显示,动脉粥样硬化+硼替佐米组与动脉粥样硬化组之间VCAM-1表达存在差异,但各组之间ICAM-1表达和动脉粥样硬化病变无差异。

结论

在进展性动脉粥样硬化模型大鼠中连续四天给予50μg/kg的硼替佐米可抑制VCAM-1表达,尽管它不影响ICAM-1表达且不能抑制动脉粥样硬化病变形成。

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Critical roles of inflammation in atherosclerosis.炎症在动脉粥样硬化中的关键作用。
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