两种糖尿病前期大鼠模型比较
投稿时间:2025-07-03  修订日期:2025-07-09  点此下载全文
引用本文:肖颖馥,刘佳莉,王能,曹淼,李鑫辉,何清湖.两种糖尿病前期大鼠模型比较[J].医学研究杂志,2025,54(11):122-127
DOI: 10.11969/j.issn.1673-548X.2025.11.022
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作者单位
肖颖馥 湖南中医药大学中医学院 长沙,410208 
刘佳莉 湖南中医药大学中医学院 长沙,410208 
王能 湖南中医药大学中医学院 长沙,410208 
曹淼 湖南中医药大学中医学院 长沙,410208 
李鑫辉 湖南中医药大学中医学院 长沙,410208 
何清湖 湖南中医药大学中医学院 长沙,410208
湖南医药学院 怀化,418000 
基金项目:湖南省自然科学基金资助项目(2023JJ50435,2022JJ40298);湖南中医药大学大学生创新创业训练计划项目(2024-185)
中文摘要:目的 采用两种不同的方式构建糖尿病前期的大鼠动物模型,比较血糖、血脂、血清胰岛素、胰腺形态以及相关生化指标差异,以期为糖尿病前期合理动物模型选择提供实验依据。方法 30只SD大鼠随机分为正常组、高脂模型组和高脂联合链脲佐菌素(streptozotocin, STZ)模型组,每组各10只。正常组用普通饲料喂养,高脂模型组予以高脂饲料喂养,高脂联合STZ模型组在高脂饲料喂养基础上腹腔注射STZ 20mg/kg。造模成功后处死大鼠,口服葡萄糖耐量试验(oral glucose tolerance test, OGTT)评估糖耐量情况,苏木精-伊红染色(hematoxylin-eosin staining, HE染色)观察胰腺、肝组织病理变化,生化分析仪检测血清高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)、甘油三酯(triglyceride, TG)、总胆固醇(total cholesterol, TC)水平,酶联免疫吸附试验(enzyme-linked immunosorbent assay, ELISA)法检测血清空腹胰岛素(fasting insulin, FINS)、超氧化物歧化酶(superoxide dismutase, SOD)、丙二醇(malondialdehyde, MDA)、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、白细胞介素-6(interleukin-6, IL-6)水平。结果 与正常组比较,高脂模型组大鼠餐后2h血糖、OGTT血糖-时间曲线下面积、FINS、TC、TG、LDL-C、MDA、IL-6、TNF-α水平升高(P<0.05),SOD水平下降(P<0.05)。HE染色结果显示,胰岛形态不规则,β细胞分布不均匀;与正常组比较,高脂联合STZ模型组大鼠空腹血糖、餐后2h血糖、OGTT血糖-时间曲线下面积、FINS、TC、TG、LDL-C、MDA、TNF-α水平升高(P<0.05),SOD水平下降(P<0.05)。HE染色结果显示,胰岛形态不规则,β细胞分布不均匀、细胞变形。与高脂模型组比较,高脂联合STZ模型组大鼠TC水平更高(P<0.05),TNF-α水平降低(P<0.05)。结论 两种造模方式均可成功造模糖尿病前期状态,但高脂模型更适用于“葡萄糖耐量减退”状态,高脂联合STZ模型更适用于“空腹血糖受损+葡萄糖耐量减退”状态,两者在表型上存在一定差异。
中文关键词:糖尿病前期 高脂饮食 动物模型 比较研究
 
Comparative of Two Prediabetic Rat Models.
Abstract:Objective The rat model of prediabetes was established by two different methods, and the differences of blood glucose, blood lipid, serum insulin, pancreatic morphology and related biochemical indicators were compared, so as to provide experimental evidence for the rational selection of animal models for prediabetes. Methods Thirty SD rats were randomly divided into three groups:normal group, high-fat model group, and high-fat combined with streptozotocin (STZ) model group, with 10 rats in each group.The normal group was fed with ordinary diet, the high-fat model group was fed with high-fat diet, and the high-fat combined with STZ model group was intraperitoneally injected with 20mg/kg STZ. The rats were killed after successful modeling. Oral glucose tolerance test (OGTT) was performed to evaluate glucose tolerance. Pathological changes of pancreatic and liver tissues were observed by hematoxylin-eosin (HE) staining. Serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), serum total cholesterol (TC) levels were detected by biochemical analyzer. Serum levels of fasting serum insulin (FINS), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Results Compared with the normal group, the 2hour post-meal blood glucose, the peak area under the curve (AUC) of OGTT blood glucose-time, FINS, TC, TG, LDL-C, MDA, IL-6 and TNF-α levels of rats in high-fat moedl group were increased (P<0.05), and the SOD level was decreased (P<0.05). The results of HE staining showed that islet morphology was irregular and the distribution of β cells was uneven. Compared with the normal group, the fasting blood glucose, 2hour post-meal blood glucose, the peak AUC of OGTT blood glucose-time, FINS, TC, TG, LDL-C, MDA and TNF-α levels of rats in high-fat combined with STZ model group were increased (P<0.05), and the SOD level was decreased (P<0.05). The results of HE staining showed that the islet morphology was irregular, the distribution of β cells was uneven, and the cells were deformed. Compared with the high-fat model group, the TC level in the high-fat combined with STZ model group was higher (P<0.05), and the TNF-α level was decreased (P<0.05). Conclusion Both two modeling methods can successfully create a prediabetic state, but the high-fat model is more suitable for impaired glucose tolerance, and the high-fat combined with STZ model is more suitable for impaired fasting glucose+impaired glucose tolerance state. There is a certain difference in phenotype between the two models.
keywords:Prediabetes  High-fat diet  Animal model  Comparative study
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