AIMS Imatinib is an effective tyrosine kinase inhibitor which has different therapeutic actions. The recent work demonstrated the possible beneficial effects of imatinib on the progression of atherosclerosis, endothelial dysfunction, and hypercholesterolemia-associated liver damage in rabbits. MAIN METHODS Animals had been distributed in 4 groups: group 1 (non-treated): animals fed regular diet; group 2 high cholesterol [HC]: animals fed 1% cholesterol supplemented diet for 30 days; group 3 (HC-Imatinib): animals fed 1% cholesterol supplemented diet+imatinib (0.01 g/kg daily, p.o) for 30 days; group 4 (Imatinib): animals fed regular diet with imatinib (0.01 g/kg daily, p.o). After thirty days, tissue samples and blood were isolated to be detected biochemically, histologically, and for in vitro analysis. KEY FINDINGS HC exhibited significant elevations in serum lipid parameters, CRP, ALT, AST and ALP. Additionally, HC induced significant increases for aortic and hepatic MDA, aortic NO and hepatic PDGFR-β, while significantly exhibited reductions in aortic and hepatic GSH, SOD and hepatic PPARγ1. Moreover, HC produced impairment in ACh-enhanced aortic relaxation and aortic pathological changes. Histopathological examination of HC-fed rabbits revealed hepatic steatosis compared with non-treated group. Imatinib administration exhibited significant decreases in serum lipid parameters, CRP, ALT, AST and ALP. Additionally, imatinib induced significant decreases for aortic and hepatic MDA, aortic NO and hepatic PDGFR-β, while significantly exhibited elevations in aortic and hepatic GSH, SOD and hepatic PPARγ1 compared with HC animals. Furthermore, imatinib significantly protected against HC produced attenuation in ACh-induced aortic relaxation and pathological changes in aortic and hepatic tissues. Interestingly, imatinib could return serum CRP, ALP, hepatic SOD and PDGFR-β to basal values. SIGNIFICANCE The recent observation reports that imatinib could have beneficial effect against atherosclerosis progression, vascular malfunction, and liver damage in high cholesterol diet (HCD)-fed rabbits.

中文翻译：

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伊马替尼对兔高胆固醇血症引起的动脉粥样硬化、内皮功能障碍和肝损伤的潜在作用。

AIMS 伊马替尼是一种有效的酪氨酸激酶抑制剂，具有不同的治疗作用。最近的工作证明了伊马替尼对兔动脉粥样硬化、内皮功能障碍和高胆固醇血症相关肝损伤进展的可能有益作用。主要方法 动物被分为 4 组：第 1 组（未治疗）：正常饮食的动物；第 2 组高胆固醇 [HC]：动物喂食 1% 胆固醇补充饮食 30 天；第 3 组（HC-伊马替尼）：动物喂食 1% 胆固醇补充饮食+伊马替尼（每日 0.01 g/kg，口服）30 天；第 4 组（伊马替尼）：用伊马替尼（每天 0.01 克/千克，口服）定期喂养动物。三十天后，分离组织样本和血液以进行生化、组织学检测和体外分析。主要发现 HC 显示血清脂质参数、CRP、ALT、AST 和 ALP 显着升高。此外，HC 显着增加主动脉和肝脏 MDA、主动脉 NO 和肝脏 PDGFR-β，同时显着降低主动脉和肝脏 GSH、SOD 和肝脏 PPARγ1。此外，HC 对 ACh 增强的主动脉松弛和主动脉病理变化产生损害。与未治疗组相比，HC 喂养兔的组织病理学检查显示肝脂肪变性。伊马替尼给药表现出血清脂质参数、CRP、ALT、AST 和 ALP 的显着降低。此外，与 HC 动物相比，伊马替尼显着降低主动脉和肝脏 MDA、主动脉 NO 和肝脏 PDGFR-β，同时显着升高主动脉和肝脏 GSH、SOD 和肝脏 PPARγ1。此外，伊马替尼显着防止 HC 在 ACh 诱导的主动脉松弛中产生衰减以及主动脉和肝组织的病理变化。有趣的是，伊马替尼可以使血清 CRP、ALP、肝脏 SOD 和 PDGFR-β 恢复到基础值。意义 最近的观察报告表明，伊马替尼可能对高胆固醇饮食 (HCD) 喂养的兔子的动脉粥样硬化进展、血管功能障碍和肝损伤具有有益作用。