两种动脉粥样硬化模型制备方法的比较

doi:10.3969/j.issn.1674-490X.2021.01.001

摘要/Abstract

摘要： 目的建立两种动脉粥样硬化(atherosclerosis, AS)的模型,并对建立方法进行比较研究。方法 SPF级雄性SD大鼠18只,随机分为SD正常组(SDN)和SD模型组(SDM),SPF级雄性C57BL/6J小鼠12只,ApoE^-/-小鼠24只,分为 C57BL/6J空白对照组(CN)、ApoE^-/-空白对照组(AN)和ApoE^-/-模型组(AM)。采用高脂饲料诱导法建立AS模型。比较各组鼠基本情况,检测血清中血脂、炎症因子以及脂肪酸的含量;进行主动脉窦的免疫组化;对实验鼠整体主动脉进行油红O染色以及主动脉根部切片的HE染色。结果模型组(包括SDM、AM组)鼠与正常组(包括SDN、CN、AN组)鼠在体质量、摄食和摄水方面有明显的改变(P<0.05)。与正常组相比,模型组鼠血清中TC、TG、LDL-C水平均明显升高(P<0.05),HDL-C含量明显降低(P<0.05);CRP、MCP-1、IL-1β、IFN-γ、TXB2、DPP-4含量明显升高(P<0.05),PGF-1α和GLP-1水平显著降低(P<0.05);棕榈油酸和亚油酸含量降低(P<0.05),棕榈酸、油酸、硬脂酸的含量升高(P<0.05)。模型组鼠主动脉窦中TNF-α的表达升高,StAR、PPAR-γ的表达呈阴性。AM组小鼠的动脉粥样硬化指数(atherosclerosis index,AI)是SDM组大鼠的1.67倍,SDM组内膜增厚且局部隆起,中膜弹力纤维紊乱,外膜有轻度炎症细胞浸润的现象,呈现早期的AS病理变化,而AM组有大量红色斑块沉积。结论 ApoE^-/-小鼠的AS病变程度较SD大鼠明显,并且与SD大鼠相比,AS对ApoE^-/-小鼠的脏器损伤更小,因此,ApoE^-/-小鼠更适合用于构建AS模型。

关键词: 动脉粥样硬化, 模型制备比较, 脂质代谢, 炎症反应, HE染色, 免疫组化

Abstract: Objective To establish two models for atherosclerosis(AS)and compare their establishment methods. Methods Eighteen SD rats with SPF grade were randomly divided into normal group(SDN)and model group(SDM).Twelve C57BL/6J rats and 24 ApoE^-/- rats were divided into C57BL/6J blank control group(CN), ApoE^{^-/-} blank control group(AN)and ApoE^-/- model group(AM). The AS model was established by inducting high-fat feed. The basic conditions of each group were compared and the serum lipid, inflammatory factors and fatty acids contents were detected. Immunohistochemistry of the aortic sinus was performed. Oil red O staining and haematoxylin and eosin staining were performed on the whole aorta of the experimental mice. Results There were significant changes in body mass, food intake and water intake between the model(SDM,AM group)mice and the normal(SDN,CN,AN group)mice(P<0.05). Compared with the normal group, the serum levels of TC, TG and LDL-C in the model group were significantly increased(P<0.05), while the levels of HDL-C were significantly decreased(P<0.05). CRP、MCP-1、IL-1β、IFN-γ、TXB2、DPP-4 levels were significantly increased(P<0.05 ), and PGF-1α and GLP-1 levels were significantly decreased(P<0.05). The contents of palmitoleic acid and linoleic acid decreased(P<0.05), while the contents of palmitoleic acid, oleic acid and stearic acid increased(P<0.05). In the model group, TNF-α was increased in the aortic sinus, while the expressions of StAR and PPAR-γ were negative. The atherosclerosis index(AI)of AM group mice was 1.67 times that of SDM group rats. The intima of SDM group was thickened and local uplifted, the elastic fibers of the medium membrane were disordered, and the external model showed mild inflammatory cell infiltration, presenting early AS pathological changes, while the AM group had a large amount of red plaque deposition. Conclusion The degree of AS lesions in ApoE^-/- mice is more obvious than that in SD rats. Moreover, compared with SD rats, AS has less damage to the organs of ApoE^-/- mice. Therefore, ApoE^-/- mice are more suitable for the construction of AS model.

Key words: atherosclerosis, comparison of model preparation, lipid metabolism, inflammatory response, haematoxylin and eosin staining, immunohistochemistry

中图分类号:

R965

周程艳,李倩,梁宇璇,国洪宾,赵盈秋. 两种动脉粥样硬化模型制备方法的比较[J]. 医学研究与教育, 2021, 38(1): 1-11.

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