首页|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

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

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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。
Effects of different formulations of high-fat diet on establishment of a non-alcoholic fatty liver model in rats
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 con-structing 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 corre-sponding feed for 8 weeks while modeling.The da-ta on general observation,body weight changes,and ingestion of the rats were recorded during the modeling period.After 8 weeks'feeding,liver ultra-sound,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 liv-ers was observed with the naked eyes,and the liv-er 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.RE-SULTS: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 in-dex,along with increased liver volume,blunt edge,steatosis and lipid deposition,and the trend was even more pronounced in the HFD3 group.Com-pared 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.Com-pared with the control group,the B ultrasonogra-phy showed an enlarged liver with enhanced paren-chymal echo and pipe unsharpness,CT showed that the liver and spleen CT ratio decreased obvi-ously,and the MRI images showed obvious differ-ence of liver signal intensity between in/out of phase image in the HFD1,HFD2 and HFD3 group,and the most significant imaging changes was ob-served 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 in-duced by the other two groups.NAFLD lesion is rel-atively 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.

non-alcoholic fatty liver diseasehigh-fat dietanimal modelradiologySD rat

赵梓硕、朱玉光、马燕山、李志伟、景永帅、谢英花

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河北科技大学化学与制药工程学院,石家庄 050018,河北

石家庄市中医院检验科,石家庄 050051,河北

石家庄市中医院放射科,石家庄 050051,河北

非酒精性脂肪肝病 高脂饲料 动物模型 放射学 SD大鼠

河北省自然科学基金-生物医药联合基金培育项目

H2021208003

2024

中国临床药理学与治疗学
中国药理学会

中国临床药理学与治疗学

CSTPCD北大核心
影响因子:0.97
ISSN:1009-2501
年,卷(期):2024.29(5)
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