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HL-004, the ACAT inhibitor, prevents the progression of atherosclerosis in cholesterol-fed rabbits.

机译:HL-004是ACAT抑制剂,可防止胆固醇喂养兔子的动脉粥样硬化进展。

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摘要

HL-004, N-(2,6-diisopropylphenyl) tetradecylthioacetamide, a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, was evaluated concerning the possible prevention of hyperlipidemia and atherosclerosis in 1% cholesterol-fed rabbits. HL-004 (0.2, 5 and 25 mg/kg) was orally administered once a day for 12 weeks. HL-004 inhibited the rise of total serum cholesterol at a dose of 5 mg/kg and over. In the thoracic aorta, HL-004 at the doses of 5 mg/kg and 25 mg/kg reduced the total cholesterol content by 56.3% and 84.2% compared with control, and decreased ACAT activity, dose-dependently. HL-004 also attenuated the development of aortic lesions. The area of atherosclerotic lesions was reduced by 30.3% with 5 mg/kg of HL-004 and 100% with 25 mg/kg. In this study, we suggest that the main reason for HL-004 preventing the progression of atherosclerosis is its hypocholesterolemic effect due to the inhibition of cholesterol absorption in the intestine.
机译:评估了HL-004 N-(2,6-二异丙基苯基)十四烷基硫代乙酰胺(一种新型的酰基辅酶A:胆固醇酰基转移酶(ACAT)抑制剂)在1%胆固醇喂养的兔子中可能预防高脂血症和动脉粥样硬化的可能性。 HL-004(0.2、5和25 mg / kg)每天口服一次,持续12周。 HL-004以5 mg / kg或更高的剂量抑制总血清胆固醇的升高。在胸主动脉中,与对照组相比,剂量为5 mg / kg和25 mg / kg的HL-004降低了总胆固醇含量,分别降低了56.3%和84.2%,并降低了ACAT活性。 HL-004还减弱了主动脉病变的发展。 HL-004 5 mg / kg可使动脉粥样硬化病变面积减少30.3%,25 mg / kg可使动脉粥样硬化病变面积减少100%。在这项研究中,我们建议HL-004防止动脉粥样硬化进展的主要原因是由于抑制肠道中胆固醇的吸收而产生的降胆固醇作用。

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