链脲佐菌素诱导糖尿病脑病大鼠模型的构建及评价  

Establishment and evaluation of a streptozotocin-induced diabetic encephalopathy rat model

作　　者：陈思敏 胡颖俊 闫文睿 冀乐 邵梦丽 孙泽 郑红星[1,4] 祁珊珊 Chen Simin;Hu Yingjun;Yan Wenrui;Ji Le;Shao Mengli;Sun Ze;Zheng Hongxing;Qi Shanshan(College of Biological Science and Engineering,Shaanxi University of Technology,Hanzhong 723000,Shaanxi Province,China;Qinba State Key Laboratory of Biological Resources and Ecological Environment,Shaanxi University of Technology,Hanzhong 723000,Shaanxi Province,China;Shaanxi Province Key Laboratory of Bio-resources,Hanzhong 723000,Shaanxi Province,China;Shaanxi Black Organic Food Engineering Technology Research Center,Hanzhong 723000,Shaanxi Province,China)

机构地区：[1]陕西理工大学生物科学与工程学院,陕西省汉中市723000 [2]陕西理工大学秦巴生物资源与生态环境省部共建国家重点实验室(培育),陕西省汉中市723000 [3]陕西省资源生物重点实验室,陕西省汉中市723000 [4]陕西省黑色有机食品工程技术研究中心,陕西省汉中市723000

出　　处：《中国组织工程研究》2024年第2期237-241,共5页Chinese Journal of Tissue Engineering Research

基　　金：陕西省科技厅面上项目(2020JM-601),项目负责人:祁珊珊;陕西省教育厅重点研发项目(20JY005),项目负责人:祁珊珊;秦巴生物资源与生态环境国家重点实验室项目(SXC-2013),项目负责人:郑红星;中国富硒产业研究院富硒专项研发项目(2021FXZX06),项目负责人:祁珊珊;陕西省科技厅农业类一般项目(2023-YBNY-185),项目负责人:郑红。

摘　　要：背景:目前研究较成熟的糖尿病脑病模型主要有链脲佐菌素诱导模型、高糖高脂饮食诱导模型和自发性动物模型。建立简便易行、周期短、安全有效的糖尿病脑病模型对其发病机制的深入探讨和治疗药物的筛选有重要的作用。目的:进一步验证链脲佐菌素诱导糖尿病脑病大鼠模型的方法并对其进行评价。方法:将20只SD大鼠随机分为对照组(n=10)和模型组(n=10),模型组大鼠左下腹腔一次性注射45 mg/kg链脲佐菌素建立糖尿病实验动物模型,对照组大鼠用等量的柠檬酸缓冲液代替注射。实验期间监测大鼠体质量、饮食量、饮水量和血糖,8周后检测葡萄糖耐量和氧化应激水平,并比较脑组织病理变化及凋亡蛋白的表达情况。结果与结论:①与对照组相比,模型组大鼠饮食量、饮水量、脑指数、血糖和血糖曲线下面积显著升高、体质量明显下降(P<0.01);②脑组织病理学显示,模型组大鼠存活神经细胞数量明显减少(P<0.01),神经细胞病理损伤明显高于对照组;③模型组大鼠较对照组血清超氧化物歧化酶、过氧化氢酶和谷胱甘肽活力均明显降低(P<0.01),氧化活性丙二醛的浓度明显升高(P<0.05);④脑组织中凋亡相关蛋白Bax和Caspase-3表达水平增加,Bcl-2表达水平降低(P<0.01);⑤结果说明,注射45 mg/kg链脲佐菌素8周后可以使糖尿病大鼠脑组织有明显的病理损伤,成功构建糖尿病脑病大鼠模型。BACKGROUND:Animal models of diabetic encephalopathy that have been studied mainly include streptozotocin-induced model,high-sugar and high-fat dietinduced model and spontaneous animal model.Establishing a simple,easy,short-cycle,safe and effective model of diabetic encephalopathy can help to explore the subsequent pathogenesis and screen therapeutic drugs.OBJECTIVE:To further explore and evaluate the method of building diabetic encephalopathy rat models.METHODS:Twenty Sprague-Dawley rats were randomly divided into control(n=10)and model(n=10)groups.Rats in the model group were given a single injection of 45 mg/kg streptozotocin in the left lower abdominal cavity,and those in the control group were given the same amount of citrate buffer.During the experiment,the body mass,feed intake,water intake and blood glucose were measured.After 8 weeks,the glucose tolerance and oxidative stress levels were measured,and the pathological changes of brain tissue and the expression of apoptotic proteins were compared between groups.RESULTS AND CONCLUSION:Compared with the control group,the food intake,water intake,encephalization quotient,blood glucose and area under the blood glucose curve were significantly increased in the model group,while the body mass decreased significantly(P<0.01).Histopathological examination of the brain showed that compared with the control group,the number of surviving nerve cells was significantly reduced in the model group(P<0.01),with more significant pathological damage of nerve cells.Compared with the control group,the activities of serum superoxide dismutase,catalase and glutathione in the model group were significantly decreased(P<0.01),and the content of oxidative malondialdehyde was significantly increased(P<0.05).The expression levels of apoptosis-related proteins Bax and Caspase-3 in brain tissue increased in the model group compared with the control group,while the expression of Bcl-2 decreased(P<0.01).In conclusion,an 8-week injection of 45 mg/kg streptozotocin can cause obvious patholo

关 键 词：糖尿病脑病 链脲佐菌素 动物模型 脑组织 大鼠 高血糖 氧化应激 神经细胞凋亡 

分 类 号：R459.9[医药卫生—治疗学] R-332[医药卫生—临床医学] R587.2