塞来昔布与小剂量阿司匹林合用对动脉粥样硬化的影响

目的　观察特异性环氧合酶2抑制剂塞来昔布与小剂量阿司匹林合用对小鼠动脉粥样硬化进展的影响。方法　8周龄雄性载脂蛋白E基因敲除的C5 7BL/ 6小鼠分为阿司匹林组(n =10 )、阿司匹林+塞来昔布组(n=11)及安慰剂对照组(n =8) ,均予西方饮食喂养,分别以阿司匹林、阿司匹林+塞来昔布及安慰剂灌胃;同龄同遗传背景野生型小鼠为正常对照组(n =6 ) ,常规饲料喂养。16周龄处死,酶法分析测定血脂,冰冻切片光镜下定位主动脉根部,油红O染色评估粥样硬化病变情况。结果　两用药组及安慰剂组血脂水平均显著高于正常对照组(P<0 .0 1) ,两用药组总胆固醇水平略低于安慰剂组(30 .2±5 .5mmol/L与2 8.6±6 .2mmol/L对37.8±8.1mmol/L ,P<0 .0 5 ) ,而甘油三酯水平高于安慰剂组(3.4±0 .5mmol/L与3.0±0 .6mmol/L对2 .3±0 .7mmol/L ,P <0 .0 5 ) ,两用药组之间血脂水平无差异。主动脉根部横切面油红O染色显示,各用药组及安慰剂组见明显粥样硬化斑块形成;用药组的斑块面积及管腔狭窄度均较安慰剂组显著降低(P <0 .0 1) ,而残余管腔显著扩大(P <0 .0 1) ,且阿司匹林+塞来昔布组的斑块面积较阿司匹林组进一步减小(0 .0 4 2±0 .0 2 6mm2 对0 .0 6 8±0 .0 2 2mm2 ,P <0 .0 5 )。结论　阿司匹林可一定程度上降低载脂蛋白E基因

Effects of Celecoxib, a Specific Cyclooxygenase-2 Inhibitior, Together with Low-dose Aspirin on Atherosclerosis Progression in Apolipoprotein-E knockout Mice

Aim To observe the effects of treatment with celecoxib, a specific cyclooxygenase-2 inhibitor, together with low-dose aspirin on atherosclerosis progression in an apolipoprotein-E knockout (ApoE -/-) mice model. Methods 8-week-old ApoE -/- mice fed on a western-diet were devided into group aspirin (n=10), group aspirin+celecoxib (n=11), and group placebo (n=8). Aspirin, aspirin+celecoxib and placebo were given respectively by oral gavage. Wildtype mice fed on a normal diet were as normal control group (n=6).At 16 weeks of age, serum total cholesterol (TC) and triglyceride (TG) were determined, atherosclerotic lesions in arotic root were evaluated by oil red O staining. Results A small difference in serum TC and TG levels was found either in group aspirin or in group aspirin+celecoxib compared with group placebo (30.2±5.5 mmol/L and 28.6±6.2 mmol/L vs 37.8±8.1 mmol/L,p<0.05, p<0.05); However, there was no significant difference between the two treatment groups. Oil red O staining showed that mean plaque size in arotic root was significant smaller either in group aspirin+celecoxib or in group aspirin compared with group placebo (p<0.01), and it was much smaller in group aspirin+celecoxib (0.042±0.026 mm2 vs 0.068±0.022 mm2, p<0.05). Conclusions Aspirin can slightly decrease serum level of TC in ApoE -/- mice; Celecoxib, together with low dose aspirin, can reduce the progression of atherosclerosis to a much more extent