[1]张玉倩 刘笑迎 贾岩辉 王群 陈婡 王长德 曲红.糖尿病性脑内微小病变大鼠模型的建立 及其病理学研究[J].国际内分泌代谢杂志,2019,39(02):83-86.[doi:10.3760/cma.j.issn.1673-4157.2019.02.003]
 Zhang Yuqian,Liu Xiaoying,Jia Yanhui,et al.Establishment and pathological studies of a rat model of intracerebral microlesions associated with diabetes[J].International Journal of Endocrinology and Metabolism,2019,39(02):83-86.[doi:10.3760/cma.j.issn.1673-4157.2019.02.003]
点击复制

糖尿病性脑内微小病变大鼠模型的建立 及其病理学研究()
分享到:

《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
39
期数:
2019年02期
页码:
83-86
栏目:
论著
出版日期:
2019-03-20

文章信息/Info

Title:
Establishment and pathological studies of a rat model of intracerebral microlesions associated with diabetes
作者:
张玉倩1 刘笑迎2 贾岩辉1 王群1 陈婡2 王长德2 曲红2
1山东省滨州市中心医院神经内科 251700; 2上海中医药大学附属上海市中西医结合医院神经内科 200082
Author(s):
Zhang Yuqian1 Liu Xiaoying2 Jia Yanhui1 Wang Qun1 Chen Lai2 Wang Changde2 Qu Hong2
1Department of Neurology, Binzhou Central Hospital, Shandong Province, Binzhou 251700, China; 2Department of Neurology, Shanghai Integrated TCM Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
关键词:
糖尿病 脑内微小病变 大鼠
Keywords:
Diabetes mellitus Intracerebral microlesion Rat
DOI:
10.3760/cma.j.issn.1673-4157.2019.02.003
摘要:
目的 建立糖尿病性脑内微小病变大鼠模型,进一步进行病理学分析。方法 健康雄性1月龄Wistar大鼠12只,采用随机数字表法分为正常对照组(n=6)和模型组(n=6),参照赵宝珍改良的2型糖尿病模型建立方法先建立糖尿病大鼠模型,采用反复低血糖法诱导大鼠脑内微小病变的发生,饲养至6月龄进行大鼠头颅磁共振(MR)检查,筛选脑内微小病变个数≥6个、且无梗死病灶或定位体征的大鼠,定义为造模成功。造模成功后对大鼠脑组织进行病理学分析,并计数镜下低氧诱导因子-1α(HIF-1α)阳性细胞数目。结果 与正常对照组相比,模型组血糖水平以及每10 g血红蛋白吸光度明显升高(t=-11.141、-38.392, P均<0.01); 脑内微小病变数目增多(t=-6.104,P<0.01)。模型组脑内微小病变的病理改变主要为神经元数目减少,神经胶质细胞增生并肿胀,部分有微出血,并且HIF-1α阳性表达细胞数多于正常对照组(t=-663.45,P<0.01)。结论 在糖尿病大鼠模型基础上通过反复低血糖法诱导,可建立糖尿病性脑内微小病变大鼠模型,用于探究糖尿病性脑内微小病变的发病机制及治疗靶点。
Abstract:
Objective To establish the rat model of intracerebral microlesions associated with diabetes, which was used for further pathological analysis.Methods A total of twelve healthy male Wistar rats were randomly divided into normal control group(n=6)and model group(n=6)according to random number table method. Initially, the diabetic rat model was established referring to the improved Zhao Baozhen's method. Then the intracerebral microlesions was induced by recurrent hypoglycemia, and the cranial magnetic resonance(MR)examination was performed in rats until the age of 6 months.The rats showed more than six microlesions and no infarctions in the brain were defined as successful models. Pathological analysis of brain tissue from rats was conducted and the number of hypoxia inducible factor-1α(HIF-1α)positive cells were counted under the microscope.Results Compared with normal control group,blood glucose and absorbance of hemoglobin per 10 g in model group were significantly higher(t=-11.141, -38.392,all P<0.01). Moreover, the microlesions in model group were more than those in normal control group(t=-6.104, P<0.01).The pathological changes of microlesions in model group included decreasing number of neurons, the proliferation and swelling of glial cells, as well as some microhemorrhage. The HIF-1α positive cells in model group were more than those in normal control group(t=-663.45, P<0.01). Conclusion The rat model of diabetic intracerebral microlesions can be established by using the method of recurrent hypoglycemia, this model can be used to explore the pathogenesis of diabetic microlesions in the brain and potential therapeutic targets.

参考文献/References:

[1] 曲红,西丸雄也.从脑内微小病变探讨中风“治未病”客观依据的研究[J].天津中医药,2008,25(4):292-295.
[2] 澤田徹,種田二郎,岡本幸市,ほか.無症候性脳血管障害の診断基準に関する研究[J].脳卒中,1997,19(6):489-493.
[3] Zhu YC,Tzourio C,Soumaré A,et al.Severity of dilated Virchow-Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: a population-based study[J].Stroke,2010,41(11):2483-2490.DOI:10.1161/STROKEAHA.110.591586.
[4] 曲红,周蔓蔓,张玉倩,等.MRI上血管周围间隙与血管性危险因子及脑梗死发病的相关性[J].中国医学影像学杂志,2012,20(9):64-65. DOI:10.3969/j.issn.1005-5185.2012.09.003.
[5] 赵宝珍,白秀平,荣青峰,等.实验性2型糖尿病大鼠模型的研究[J]. 中国药物与临床, 2002,2(6):383-385.DOI:10.3969/j.issn.1671-2560.2002.06.013.
[6] Tanne D,Koren-Morag N,Goldbourt U.Fasting plasma glucose and risk of incident ischemic stroke or transient ischemic attacks: a prospective cohort study[J].Stroke,2004,35(10):2351-2355.DOI:10.1161/01.STR.0000140738.94047.55.
[7] Xu Y,Wang L,He J,et al.Prevalence and control of diabetes in Chinese adults[J].JAMA,2013,310(9):948-959.DOI:10.1001/jama.2013.168118.
[8] Yang Z,Xing X,Xiao J,et al.Prevalence of cardiovascular disease and risk factors in the Chinese population with impaired glucose regulation: the 2007-2008 China national diabetes and metabolic disorders study[J].Exp Clin Endocrinol Diabetes,2013,121(6):372-374.DOI:10.1055/s-0033-1341520.
[9] Pinto A,Tuttolomondo A,Di Raimondo D,et al.A case control study between diabetic and non-diabetic subjects with ischemic stroke[J].Int Angiol,2007,26(1):26-32.
[10] Knopman DS,Griswold ME,Lirette ST,et al.Vascular imaging abnormalities and cognition: mediation by cortical volume in nondemented individuals: atherosclerosis risk in communities-neurocognitive study[J].Stroke,2015,46(2):433-440.DOI:10.1161/STROKEAHA.114.007847.
[11] Bohuslavova R,Kolar F,Sedmera D,et al.Partial deficiency of HIF-1α stimulates pathological cardiac changes in streptozotocin-induced diabetic mice[J].BMC Endocr Disord,2014,14:11.DOI:10.1186/1472-6823-14-11.
[12] Ortega A,Fernández A,Arenas MI,et al.Outcome of acute renal injury in diabetic mice with experimental endotoxemia: role of hypoxia-inducible factor-1α[J].J Diabetes Res,2013,2:254529-254536.DOI:10.1155/2013/254529.
[13] Nakagawa K,Kohara T,Uehata Y,et al.PIAS3 enhances the transcriptional activity of HIF-1α by increasing its protein stability[J].Biochem Biophys Res Commun,2016,469(3):470-476.DOI:10.1016/j.bbrc.2015.12.047.
[14] Daneman R.The blood-brain barrier in health and disease[J].Ann Neurol,2012,72(5):648-672. DOI:10.1002/ana.23648.

相似文献/References:

[1]郑少雄.罗格列酮和心血管风险——近期文献解读[J].国际内分泌代谢杂志,2007,(04):231.
[2]凌厉,朱本章.胰岛素类似物安全性研究进展[J].国际内分泌代谢杂志,2007,(04):234.
[3]李颖,刘东方.餐后1小时血糖升高的意义及干预[J].国际内分泌代谢杂志,2007,(04):235.
[4]崔巍,施秉银.内质网应激介导β细胞生存/死亡的研究进展[J].国际内分泌代谢杂志,2007,(04):256.
[5]杨叶虹,胡仁明.SELDI-TOF-MS技术及其在糖尿病研究中的应用[J].国际内分泌代谢杂志,2007,(04):261.
[6]高妍.针对华人糖尿病特点优化降糖方案[J].国际内分泌代谢杂志,2007,(04):269.
[7]杨志霞,郭莹辉,杨永生,等.胰岛素泵和多次皮下注射治疗糖尿病的比较[J].国际内分泌代谢杂志,2007,(04):273.
[8]周建英,马向华.胃旁路术减肥同时改善糖代谢的机制[J].国际内分泌代谢杂志,2007,(04):285.
[9]李翠柳,朱大龙.破译肠道代谢信息,驱动治疗革新[J].国际内分泌代谢杂志,2014,(06):383.[doi:10.3760/cma.j.issn.1673-4157.2014.06.006]
 Li Cuiliu*,Zhu Dalong..Deciphering metabolic messages from the gut drives therapeutic innovation[J].International Journal of Endocrinology and Metabolism,2014,(02):383.[doi:10.3760/cma.j.issn.1673-4157.2014.06.006]
[10]袁捷 姜云生 杜彦丽 王肃.1型糖尿病对小鼠早孕时期子宫肌层结构和细胞增殖的影响[J].国际内分泌代谢杂志,2015,(01):6.[doi:10.3760/cma.j.issn.1673-4157.2015.01.002]
 Yuan JieJiang YunshengDu YanliWang Su.Effects of type 1 diabetes on the muscularis structure and cell proliferation of uterine in mice during early pregnancy[J].International Journal of Endocrinology and Metabolism,2015,(02):6.[doi:10.3760/cma.j.issn.1673-4157.2015.01.002]

备注/Memo

备注/Memo:
通信作者:刘笑迎, Email:liuxiaoying2005@126.com
基金项目:上海市科学技术委员会中医引导类课题(16401931600); 上海市虹口区卫生和计划生育委员会重点课题(虹卫1702-05); 山东省中医药管理局中医药科技发展计划项目(2017-499)
Corresponding author: Liu Xiaoying, Email: liuxiaoying2005@126.com
Fund program:Science and Technology Commission Shanghai Municipality Guiding Project of TCM(16401931600); Important Project of Shanghai Hongkou District Health Commission(1702-05); Shandong Administration of Traditional Chinese Medicine Science and Technology Development Project(2017-499)
更新日期/Last Update: 2019-03-20