糖尿病大鼠反复严重低血糖后脑内代谢改变的1H NMR波谱研究

doi:10.11969/j.issn.1673-548X.2017.07.008

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题名	糖尿病大鼠反复严重低血糖后脑内代谢改变的1H NMR波谱研究
其他题名	Cerebral Metabolism in the Diabetic Rats after Recurrent Profound Hypoglycemia: an 1H Nuclear Magnetic Resonance Spectroscopy Study
作者	刘锟1; 王永姣 2; 黄小燕 1; 周永进 1; 叶信健1; 付玉川1; 杜美美1; 高红昌3; 严志汉1
发表日期	2017-07-15
发表期刊	医学研究杂志影响因子和分区
语种	中文
原始文献类型	学术期刊
关键词	糖尿病低血糖脑损伤磁共振波谱代谢胶质纤维酸性蛋白
其他关键词	Diabetes ; Hypoglycemia ; Brain Injury ; Magnetic resonance spectroscopy ; Metabolism ; GFAP
摘要	目的运用基于~1H NMR的代谢组学方法研究糖尿病大鼠反复严重低血糖后脑内代谢的变化,并结合病理学检查探讨糖尿病大鼠反复严重低血糖脑损伤的发病机制。方法 24只7周龄Sparague Dawley大鼠随机分为实验组和对照组,每组12只。实验组大鼠禁食12h,通过腹腔注射链脲佐菌素溶液(65ml/kg)造成糖尿病,此后连续5天每天腹腔注射胰岛素(4~8U/kg)诱导严重低血糖。对照组则在此期间分别给予等量柠檬酸缓冲液及生理盐水。每组6只大鼠的海马和额叶、顶叶、枕叶进行~1H NMR波谱检测,另外6只进行胶质纤维酸性蛋白(GFAP)染色。采用t检验进行统计学处理。结果实验组大鼠诱导低血糖前血糖值为12.25±2.64mmol/L,注射胰岛素后1h血糖值为1.11±0.45mmol/L,对照组实验期间血糖值6.88±0.59mmol/L。所有实验组大鼠在严重低血糖期间临床表现为精神不振、活动度减弱、体温下降、肢体松软、皮肤苍白,4只严重者出现抽搐。相比对照组,各脑区乳酸浓度升高、谷氨酰胺下降,同时枕叶丙氨酸和琥珀酸含量下降,额、顶叶还存在胆碱含量下降。GFAP染色显示,相比对照组,实验组各脑区的星形胶质细胞数目均显著性增加(P<0.05)。结论糖尿病反复严重低血糖后脑内代谢改变且存在区域性差异,以能量代谢障碍及谷氨酸-谷氨酰胺循环紊乱为主,糖尿病反复严重低血糖后主要引起神经胶质细胞损伤,代谢改变与神经胶质细胞损伤相关。
其他摘要	Objective A high resolution 1H nuclear magnetic resonance spectroscopy(1 H NMR) of metabonomics approach was applied to detect the metabolic changes in the diabetic rats after recurrent profound hypoglycemia,and combined with histopathological examination to explore the mechanism of repeated severe hypoglycemic brain injury in the diabetic rats.Methods Seven-week-old male Sprague-Dawley rats were randomly assigned to normal control group(Con,n =12) and diabetes comorbid recurrent hypoglycemia group(DH,n =12).All the rats were fasted for 12 hours.After that,DH group rats received intraperitoneal injections of streptozotocin(65mg/kg) to induce diabetes,then they were given an insulin injection ip at a dose of 4-8U/kg to induce severe hypoglycemia for 5 consecutive days.Con group received the same amount of sodium citrate buffer and normal saline respectively.Glial fibrillary acidic portein(GFAP) was used to study the changes of glial cells in six rats hippocampus,frontal lobe,parietal lobe and occipital lobe in each group,and high resolution MRS was used to study the metabolic changes in these four brain regions of the others rats.The difference between two groups was compared by t test.Results Changes of plasma glucose concentrations:the glucose levels of DH group before and 1 hour after the injection of insulin were 12.25 ±2.64mmol/L and 1.11 ± 0.45mmol/L respectively.During the experiment,the blood glucose values of the Con group was 6.88 ± 0.59mmol/L.Clinical manifestations:during severe hypoglycemia,depression,hypokinesia,hypothermia,soft body and pale skin were noted in the DH animals,and four of them had seizure.Metabolic changes:compared to the Con group,significantly increased level of lactate and decreased level of glutamine were found in the four brain regions.Besides,the concentration of alanine and succinate was sharply decreased in the ocipital lobe,and Choline was decreased in the frontal and parietal lobe.GFAP staining:compared to the Con group,the number of astrocytes in the hippocampus,frontal,parietal and occipital lobe of DH group rats were significantly increased (P ＜ 0.05),of which the maximum number of GFAP positive cells was in the hippocampus.Conclusion Diabetes comorbid recurrent severe hypoglycemia induces regional specific metabolic changes in the brain,which mainly contain dysfunction of energy metabolism and Glu-Gln cycle.Diabetes comorbid recurrent severe hypoglycemia causes glia cells injury,which may associate with the metabolic changes.
资助项目	国家自然科学基金资助项目（81400863）;浙江省医药卫生计划项目（2014KYB159、2015KYB250）;浙江省温州市科技局社会发展科学研究项目（Y20130175、Y20140028）
ISSN	1673-548X
卷号	46 期号:07 页码:30-35+112
DOI	10.11969/j.issn.1673-548X.2017.07.008
页数	7
收录类别	CNKI ; 万方 ; 维普 ; ISTIC
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文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/39701
专题	第一临床医学院（信息与工程学院）、附属第一医院_影像医学与核医学_放射科药学院（分析测试中心）附属第二医院第二临床医学院、附属第二医院、育英儿童医院附属第二医院_放射科
作者单位	1.温州医科大学附属第二医院育英儿童医院放射科; 2.武汉市妇女儿童医疗保健中心CT&MRI室; 3.温州医科大学药学院
第一作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 放射科
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	刘锟,王永姣,黄小燕,等. 糖尿病大鼠反复严重低血糖后脑内代谢改变的1H NMR波谱研究[J]. 医学研究杂志,2017,46(07):30-35+112.
APA	刘锟., 王永姣., 黄小燕., 周永进., 叶信健., ... & 严志汉. (2017). 糖尿病大鼠反复严重低血糖后脑内代谢改变的1H NMR波谱研究. 医学研究杂志, 46(07), 30-35+112.
MLA	刘锟,et al."糖尿病大鼠反复严重低血糖后脑内代谢改变的1H NMR波谱研究".医学研究杂志 46.07(2017):30-35+112.

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