糖尿病发展过程中大鼠血浆主要生物标记物的动态变化  

Dynamic changes of major biomarkers in rats plasma during the development of diabetes

作　　者：王艳[1] 赵瑛[1] 周游[1] 刘琳[1] 

机构地区：[1]哈尔滨商业大学药学院,黑龙江哈尔滨150000

出　　处：《沈阳药科大学学报》2014年第5期391-395,共5页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(81373548);黑龙江省研究生创新基金资助项目(YJSCX2012-147HLJ);黑龙江省自然科学基金资助项目(H201382)

摘　　要：目的研究糖尿病发展过程中大鼠血浆β-淀粉样蛋白42（amyloid beta 42,Aβ42）、胰岛素和血糖的动态变化;初步探讨在糖尿病发展过程中胰岛素和血糖对Aβ42的影响,并分析糖尿病发展成为认知障碍的风险。方法腹腔注射链脲佐菌素（streptozotocin,STZ）复制实验性糖尿病大鼠模型,以血糖浓度≥16.7 mmol·L-1确定模型成立。实验分为正常组与模型组。建模前后共采集5次血液,每次间隔15 d。建模60 d,代谢笼测大鼠24 h食量、水量、尿量和粪便量;建模70 d,八臂迷宫实验测定大鼠觅食时间、参考记忆错误次数和工作记忆错误次数。用葡萄糖氧化酶法和酶联免疫吸附法测血糖、胰岛素和Aβ42的含量。结果 STZ复制的糖尿病大鼠模型稳定。模型组大鼠食量、水量、尿量和粪便量明显高于对照组（P〈0.01）;八臂迷宫实验：与对照组比较,模型组大鼠觅食时间、参考记忆错误频率和平均探究时间均有显著性差异（P〈0.05）,工作记忆错误频率高于对照组,但是无统计学意义。模型成立初期Aβ42随胰岛素增多而降低,建模45 d,Aβ42含量最高,之后下降。结论建模70 d,模型组大鼠学习记忆能力明显低于对照组,糖尿病大鼠患认知障碍的风险明显增高;糖尿病初期,模型成立45~75 d,为给予药物干预治疗的最佳时期;临床上可以通过同时检测胰岛素和Aβ42判断糖尿病是否向认知障碍发展。Objective To study the dynamic changes of Aβ42（ amyloid beta,Aβ42）,insulin and glucose in rats＇ plasma during the development of diabetes. To preliminarily study the influence of insulin and blood sugar on Aβ42 in the process of development of diabetes,and analyze the risk of cognitive impairment in diabetes rats. Methods The rats model of diabetes w as produced by injecting STZ（ streptozotocin,STZ） in rat peritoneal cavity,and the blood glucose concentration of the established model should be no less than 16. 7 mmol·L- 1. The experiments w ere divided into the normal group and the model group,and the blood w as collected five times at intervals of 15 d before and after modeling. After 60 d of diabetes modeling,the amount of food intake,w ater,urine and stool volume of rats for 24 h w ere measured by the metabolic cages; after 70 d,the foraging time,the number of reference memory errors and w orking memory errors of rats w ere measured by the eight-arm maze. The contents of blood sugar,insulin and Aβ42 w ere tested by glucose oxidase method and enzyme-linked immunosorbent assay. Results Diabetic rat model w as stable. Compared w ith the control group,the food intake,w ater volume,urine and feces amounts of model group rats w ere significantly increased（ P 0. 01）. Eight-arm maze test show ed that model rat＇s foraging time,reference memory error frequency and average time had significant difference from that of the control groups（ P 0. 05）; the w orking memory error frequency w as higher than that of the control group,but had no statistical significance. In the early stage,w ith the concentration of insulin increased gradually,Aβ42 decreased; the content of Aβ42 w as the highest after 45 d of diabetes,and then declined. Conclusions Compared w ith the control group,learning and memory ability of the model group rats is obviously low er after 70 d of diabetes modeling. The risk of cognitive impairment in diabetic rats is significantly increased; the best time of drug intervention therapy is

关 键 词：糖尿病 β-淀粉样蛋白42 胰岛素 血糖 认知障碍 动态变化 

分 类 号：R96[医药卫生—药理学]