硼替佐米对动脉粥样硬化模型大鼠总胆固醇、甘油三酯及腹主动脉组织病理学的影响

I. Ismawati, I. Romus, Esy Maryanti, Nopi Permatasari, Elfiah Luthfianty
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摘要

使用蛋白酶体抑制剂对动脉粥样硬化的影响可能是有益的,也可能是有害的。本研究旨在分析蛋白酶体抑制剂在进展阶段的作用。实验动物(18只)分为三组,对照组(C)给予标准饲料,P1为动脉粥样硬化诱导大鼠组,P2为动脉粥样硬化诱导大鼠组,给予蛋白酶体抑制剂。蛋白酶体抑制剂为硼替佐米,剂量为50µg/kgBW/天,在第1天和第3天腹腔注射。治疗4 d后,终止治疗,测定血清总胆固醇、血清甘油三酯,并用苏木精-伊红染色检测腹主动脉组织病理学。血清总胆固醇水平采用CHOD-PAP(胆固醇氧化酶-过氧化物酶氨基苯丙胺素)法测定,血清甘油三酯水平采用GPO-PAP(甘油磷酸酶氧化酶-苯酚-氨基安提芘过氧化物酶)法测定。采用评分系统对9个视场进行400倍放大的组织病理学评估,然后取平均值。方差分析显示,动脉粥样硬化组与对照组在血清总胆固醇、血清甘油三酯和腹主动脉组织病理学方面存在显著差异,但在动脉粥样硬化组中,除血清甘油三酯水平外,硼替佐米的使用没有显著差异。由此可见,在动脉粥样硬化进展期大鼠模型中给予50µg/kg硼替佐米4天,可降低血清甘油三酯水平,但不能抑制动脉粥样硬化病变的形成,对血清总胆固醇无影响。
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Effect of Bortezomib on Total Cholesterol, Triglycerides and Histopathology Abdominal Aorta in Rats of Atherosclerosis Model
The effects of using proteasome inhibitors on atherosclerosis could be beneficial or detrimental. This study aimed to analyze the effects of proteasome inhibitors in the progression stage. Experimental animals (18 rats) were divided into three groups, namely control (C) as a group of rats given standard feed, P1 as atherosclerosis-induced rat group, and P2 as atherosclerosis-induced rat group and given proteasome inhibitors. Proteasome inhibitor administered was bortezomib at a dose of 50µg/kgBW/day intraperitoneally on day 1 and 3. After four days of treatment, the termination and measurement of serum total cholesterol, serum triglycerides, and abdominal aorta histopathology with hematoxylin-eosin staining were carried out. Serum total cholesterol levels were measured using the CHOD-PAP (Cholesterol Oxidase-Peroxidase Aminoantypirin) method, whereas serum triglyceride levels were measured using the GPO-PAP (glycerol phosphatase oxidase−phenol4-amino antipyrene peroxidase) method. Histopathological assessment was carried out with a scoring system in 9 fields of view with a 400x magnification, which was then averaged. The ANOVA test showed significant differences in serum total cholesterol, serum triglycerides, and abdominal aortic histopathology between atherosclerosis and control groups, but there were no significant differences in the administration of bortezomib in atherosclerosis except in serum triglyceride levels. It can be concluded that the administration of 50µg/kg bortezomib for four days in the rats model of the progression stage of atherosclerosis can decrease serum triglyceride levels, although it can not inhibit the formation of atherosclerotic lesions and has no effect on serum total cholesterol. 
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