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中国临床药理学与治疗学 ›› 2024, Vol. 29 ›› Issue (5): 543-553.doi: 10.12092/j.issn.1009-2501.2024.05.009

• 基础研究 • 上一篇    下一篇

不同高脂饲料配方对建立非酒精性脂肪肝大鼠模型的影响

赵梓硕1,朱玉光2,马燕山3,李志伟1,景永帅1,谢英花1   

  1. 1河北科技大学化学与制药工程学院,石家庄  050018,河北;2石家庄市中医院检验科,石家庄  050051,河北;3石家庄市中医院放射科,石家庄  050051,河北

  • 收稿日期:2024-01-02 修回日期:2024-02-07 出版日期:2024-05-26 发布日期:2024-04-16
  • 通讯作者: 谢英花,女,博士,硕士生导师,副教授,研究方向:药物评价和药物新剂型开发。 E-mail: xieyinghua@163.com
  • 作者简介:赵梓硕,女,硕士研究生,研究方向:药物评价和药物新剂型开发。 E-mail: 1525654242@qq.com
  • 基金资助:
    河北省自然科学基金-生物医药联合基金培育项目资助项目(H2021208003)

Effects of different formulations of high-fat diet on establishment of a non-alcoholic fatty liver model in rats

ZHAO Zishuo1, ZHU Yuguang2, MA Yanshan3, LI Zhiwei1, JING Yongshuai1, XIE Yinghua1   

  1. 1 School of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, Hebei, China; 2 Department of Clinical Laboratory, Shijiazhuang Hospital of Traditional Chinese Medicine, Shijiazhuang 050051, Hebei, China; 3 Department of Radiology, Shijiazhuang Hospital of Traditional Chinese Medicine, Shijiazhuang 050051, Hebei, China
  • Received:2024-01-02 Revised:2024-02-07 Online:2024-05-26 Published:2024-04-16

摘要:

目的:比较3种不同配方高脂饲料构建非酒精性脂肪肝大鼠模型的差异,提高高脂饲料建立非酒精性脂肪肝大鼠模型的成功率,为非酒精性脂肪肝病的研究提供稳定可靠的动物模型。方法:将SPF级雄性SD大鼠随机分为普通饲料对照组、高脂饲料1组(HFD1组)、高脂饲料2组(HFD2组)、高脂饲料3组(HFD3组)。各组大鼠分别给予相应饲料8周。造模期间记录大鼠一般情况、体质量和摄食量。喂养8周后,采用腹部超声、计算机断层扫描(CT)、核磁共振成像(MRI)对大鼠肝脏进行检查。取血和肝脏,检测肝功能指标(丙氨酸氨基转移酶、天门冬氨酸氨基转移酶)、血脂指标(甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇)和炎症指标(IL-1β、IL-6、TNF-α)的变化。肉眼观察肝脏大体形态,计算其肝指数和Lee’s指数。比较上述指标在各组间的差异,综合评估不同配方高脂饲料对非酒精性脂肪肝大鼠模型的影响。结果:与对照组大鼠相比,HFD1组、HFD2组、HFD3组大鼠精神变差、活动减少、脱毛现象加重、摄食量减少、体质量明显升高,肝指数、Lee’s指数显著提高,肝脏体积增大,边缘较钝,可见脂肪变性和沉积,且以HFD3组大鼠变化最为明显;HFD1组、HFD2组、HFD3组大鼠血清谷丙转氨酶、天门冬氨酸氨基转移酶、甘油三酯、总胆固醇、低密度脂蛋白胆固醇和IL-1β、IL-6、TNF-α水平均显著升高,高密度脂蛋白胆固醇显著降低,且HFD3组更为明显;HFD1组、HFD2组、HFD3组大鼠肝脏肿大,实质回声增强,肝内管状结构显示欠清,肝和脾的CT值比值明显降低,同/反相位图上肝脏实质信号差别明显,且HFD3组对于大鼠影像学变化影响更大。结论:三种高脂饲料喂养SD大鼠8周后,均可建立非酒精性脂肪肝大鼠模型,但HFD3组诱导非酒精性脂肪肝大鼠模型优于其他两组,病变相对严重,预计维持时间也更长,更适于非酒精性脂肪肝病的机制研究和降脂药物的筛选。

关键词: 非酒精性脂肪肝病, 高脂饲料, 动物模型, 放射学, SD大鼠

Abstract:

AIM: To improve the success rate of experimental modeling of non-alcoholic fatty liver (NAFLD) in rats by high-fat diet through comparing three different formulations of high-fat diets in constructing non-alcoholic fatty liver rats model, so as to provide a reliable animal model for the study of non-alcoholic fatty liver disease. METHODS: SPF-grade male SD rats were divided into four groups randomly: control group, high-fat diet group1 (HFD1), high-fat diet group2 (HFD2), high-fat diet group3 (HFD3). Each group was given the corresponding feed for 8 weeks while modeling. The data on general observation, body weight changes, and ingestion of the rats were recorded during the modeling period. After 8 weeks' feeding, liver ultrasound, CT and MRI examination were performed for the rats of each group to check the status. Blood and liver samples were collected. Changes in liver function (ALT, AST), blood lipids (TC, TG, HDL-C, LDL-C), and inflammatory indexes (IL-1β, IL-6, TNF-α) were detected. The morphology of the livers was observed with the naked eyes, and the liver index and Lee's index were calculated at the end of 8 weeks. The effects of different high-fat diets on the establishment of NAFLD model in SD rats were comprehensively evaluated by comparing the difference of above indexes among the groups. RESULTS: Compared with the control group,rats in the HFD1, HFD2 and HFD3 groups showed poor mental deterioration, decreased activity, severe hair loss, decreased food intake, increased body weights, and significantly increased liver index and Lee's index, along with increased liver volume, blunt edge, steatosis and lipid deposition, and the trend was even more pronounced in the HFD3 group. Compared with the control group, the serum levels of ALT, AST, TC, TG, LDL-C, IL-1β, IL-6 and TNF-α were significantly increased, while the contents of HDL-C was significantly decreased in the HFD1, HFD2 and HFD3 group,especially in the HFD3 group. Compared with the control group, the B ultrasonography showed an enlarged liver with enhanced parenchymal echo and pipe unsharpness, CT showed that the liver and spleen CT ratio decreased obviously,and the MRI images showed obvious difference of liver signal intensity between in/out of phase image in the HFD1, HFD2 and HFD3 group, and the most significant imaging changes was observed in the HFD3 group. CONCLUSION: The above three kinds of high-fat diets can establish NAFLD model in SD rats after 8 weeks' feeding, the models induced by HFD3 was better than those induced by the other two groups. NAFLD lesion is relatively serious and expected to last longer in HFD3 group, which are more suitable for investigating the underlying mechanisms of non-alcoholic fatty liver disease and development of lipid-lowering drugs.

Key words: non-alcoholic fatty liver disease, high-fat diet, animal model, radiology, SD rat

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