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动脉粥样硬化以慢性血管炎症及大中动脉内皮下脂质斑块形成为主要特征,内皮细胞、平滑肌细胞、免疫细胞等均参与动脉粥样硬化的过程,随着斑块的积累,累及多种器官导致其病变[1]。动脉粥样硬化是由多种因素共同作用而形成,由脂质代谢紊乱所引起的血脂异常发挥着重要的作用,其中低密度脂蛋白胆固醇(LDL-c)升高已被证实是动脉粥样硬化的独立危险因素,低密度脂蛋白氧化后可诱导内皮细胞激活和功能障碍,促进泡沫细胞形成等[2]。随着现代生活方式及膳食营养结构的改变,高脂血症的发病率呈逐年上升,并加重了动脉粥样硬化等心脑血管疾病的进展[3]。因此,进一步研究高脂饮食所引起的动脉粥样硬化性心血管疾病具有极其重要的意义。与以人体为研究对象相比,动物具有易于管理、饮食和环境危险因素可控的优点。动脉粥样硬化的动物模型是基于高脂饮食,同时操纵胆固醇代谢的相关基因,并且引入动脉粥样硬化的额外危险因素,加速动脉斑块形成。各种动物模型现均已被用于动脉粥样硬化研究,其中鼠类和兔子的模型使用最多,其次是猪和非人灵长类动物,每种模型都有优点和局限性。由于小鼠繁殖速度快、经济成本较低以及较为容易监测动脉粥样硬化的发生,它已成为研究动脉粥样硬化的优势物种[4]。目前,高脂饲料已被广泛用于包括肥胖症、糖尿病等多种代谢性疾病的研究中,高脂饮食也可造成高脂血症,进而促进脂质在血管内膜堆积形成动脉粥样硬化。市场上存在着不同配方的高脂饲料,造模效果参差不齐,主要作用需进一步探讨。我们首先验证了一种较为常用的由普路腾公司生产的动脉粥样硬化高脂饲料对ApoE-/-小鼠动脉斑块形成的作用,并且在正常C57BL/6J小鼠上研究其对血糖血脂的影响,最后分析了不同禁食时间对正常饮食条件下血脂检测结果的影响。通过对高脂饲料对血糖血脂作用的深入研究,为小鼠动脉粥样硬化模型提供理论基础。
Effect of atherosclerotic high-fat diet on the level of glucose and lipid in mice
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摘要:
目的 研究动脉粥样硬化高脂饲料对小鼠体重、血糖血脂水平及动脉粥样硬化斑块形成的作用,并且明确禁食时间对血脂检测结果的影响。 方法 对10周龄雄性ApoE基因敲除(ApoE-/-)小鼠分别给予高脂饲料及普通饲料,4个月后观察动脉粥样硬化斑块情况;对10周龄雄性C57BL/6J小鼠分别给予普通饲料4周、普通饲料2周+高脂饲料2周、高脂饲料4周,考察动物的体重、肝脏、血糖、血脂水平,并分析正常饮食条件下取材前禁食12、6 h及不禁食条件下对血脂检测结果的影响。 结果 给予高脂饲料的ApoE-/-小鼠动脉斑块面积显著增加(P<0.01);给予高脂饲料的C57BL/6J小鼠的体重增加(P<0.01),肝脏脂肪样变;血糖、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-c)、高密度脂蛋白胆固醇(HDL-c)水平显著升高(P<0.01),而三酰甘油(TG)水平明显下降(P<0.01)。相比于禁食12 h,禁食6 h及不禁食条件下检测到的三酰甘油水平明显升高(P<0.01)。 结论 动脉粥样硬化高脂饲料可加速ApoE-/-小鼠形成动脉粥样硬化斑块,显著升高血糖、TC及LDL-c水平,但明显降低TG值。禁食时间可影响血清TG的检测结果。 Abstract:Objective To study the effects of atherosclerotic high-fat diet on body weight, blood glucose, blood lipid levels and atherosclerotic plaque formation in mice, and to determine the effect of fasting time on the results of blood lipid testing. Methods 10-week-old male ApoE knockout (ApoE-/-) mice were given high-fat diet and normal diet. The atherosclerotic plaques were observed four months later. 10 week old C57BL/6J male mice were given regular diet for 4 weeks, regular diet for 2 weeks + high-fat diet for two or four weeks. Body weight、liver、glucose, and the serum lipid levels were examined. The influence of fasting for 12 h, 6 h or no fasting on blood lipid detection results before sacrificing were studied. Results The atherosclerotic plaque area of ApoE-/- mice given high-fat diet increased significantly (P<0.01). C57BL/6J mice given high-fat diet gained weight (P<0.01). The glucose, TC, LDL-c and HDL-c were also increased in C57BL/6J mice with liver fat accumulation while the level of TG was significantly decreased(P<0.01). Compared with the fasting 12 h group, serum triglyceride (TG) was significantly increased (P<0.01)in fasting 6 h and no fasting groups. Conclusion The atherosclerotic high-fat diet can accelerate the formation of atherosclerotic plaques in ApoE-/- mice, significantly increase blood sugar, TC and LDL-c levels, but significantly reduce TG values.. The fasting time can affect serum triglyceride (TG) level. -
Key words:
- high fat diet /
- atherosclerosis /
- glucose /
- triglyceride /
- cholesterol
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