不同剂量阿司匹林对兔动脉粥样硬化斑块进展的抑制作用

Dose-dependent effects of aspirin on attenuating the progression of the atherosclerotic plaque in rabbits

目的 利用高胆固醇饮食 (2 % )并免疫损伤诱发的动脉粥样硬化斑块模型 ,评价不同剂量阿司匹林 (aspirin)对动脉粥样硬化斑块的抑制作用。方法 将 40只建立动脉粥样硬化斑块模型的新西兰大白兔随机分为阿司匹林小剂量 (4mg·kg- 1·d- 1)、中剂量 (12mg·kg- 1·d- 1)、大剂量 (2 0mg·kg- 1·d- 1)和高胆固醇四组 ,另设正常对照组 ,每组各 10只。测定指标包括 0、2、12周时的血脂和 12周时的血清C反应蛋白 (CRP)和单核细胞趋化因子 1(MCP 1)以及主动脉斑块 /内膜面积比、内 /中膜厚度比和斑块脂质含量。结果 阿司匹林小、中、大剂量组与高胆固醇组相比 ,斑块 /内膜面积比分别减少 2 0 9%、43 9%和 42 8% ,内 /中膜厚度比分别减少 49 0 %、67 1%和 69 0 % ,斑块脂质含量分别减少 2 8 8%、3 5 0 %和 48 6% (P <0 0 5～ 0 0 1) ;CRP和MCP 1也显著降低 (P均 <0 0 1)。三个治疗组间比较 ,各指标在大剂量组显著低于小剂量组 (P <0 0 5～ 0 0 1) ,但大、中剂量组间差异无显著性 (P >0 0 5)。结论 阿司匹林呈剂量相关地通过抗炎作用抑制动脉粥样硬化斑块的进展 ,效应以中剂量 (12mg·kg- 1·d- 1)

Objective To evaluate the effects of low, middle and high doses of aspirin on the progression of aortic atherosclerotic plaque in rabbits Methods Fourty New Zealand White rabbits, fed on a 2% cholesterol diet and 10% Albumin Bovine V injection, were administered aspirin at the dose of 4 mg·kg -1 ·d -1 (Ld-ASA), 12 mg·kg -1 ·d -1 (Md-ASA), 20 mg·kg -1 ·d -1 (Hd- ASA) or distilled water (H-cho) for 12 weeks Normal-diet rabbits were selected as control, there were 10 rabbits in each group The detected parameters included serum lipids, C-reactive protein (CRP) and Monocyte Chemoattactant Protein-1 (MCP-1), intima/medium thickness ratio (I/M), plaque/intima size ratio (P/I) and the lipid content of plaque (LCP) Results Compared with those in H-cho group, the dose-dependent reductions of P/I in 20 9%, 43 9% and 42 8%, I/M in 49 0%, 67 1% and 69 0%, LCP in 28 8%, 35 0% and 48 6% were found in Ld-, Md- and Hd-ASA groups respectively (P<0 05～0 01) CRP and MCP-1 decreased also in three therapy gr oups (all P<0 01) Conclusion Aspirin could dose-dependantly attenuate the progression of atherosclerotic plaque in rabbits via its anti-inflammation effects