复合B族维生素对大鼠应激性认知功能障碍发生中的保护性作用
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摘要
目的研究复合B族维生素(VBco)对大鼠应激性认知功能障碍发生过程中的保护性作用。方法选用成年雄性SD大鼠,分为5组,每组30只。实验组采用慢性不可预见性应激(CUMS)模型干预;干预组[CUMS+VBco+FA(叶酸)]:在CUMS过程中给予VBco灌胃[VB6(24 mg/kg bw·d),VB12(20μg/kg bw·d),叶酸(10mg/kg bw·d)];VBco对照组(VBco)仅给予VBco灌胃,添加量同VBco干预组;高蛋氨酸饮食组(Met)使用含1%蛋氨酸特殊饲料饲喂;空白对照组(Ctrl)不做特殊处理。动物认知功能采用旷场实验、Morris水迷宫实验、电跳台实验及探物实验检测。血浆同型半胱氨酸(Hcy)采用高效液相色谱(HPLC)分析方法检测。各组干预时程均为8w,分别于第0、2、4、6、8w末进行行为学实验,并检测血浆Hcy水平。结果持续的CUMS导致大鼠各项认知功能显著性降低,血浆Hcy水平显著性升高;应激过程中给予VBco可有效缓解大鼠认知功能下降,并翻转CUMS诱导的血浆Hcy水平上升趋势;高蛋氨酸饮食显著升高血浆Hcy水平,并降低各项认知功能;单纯给予VBco对血浆Hcy水平及认知功能无明显影响。结论慢性应激可诱导大鼠认知功能障碍,VBco能够有效缓解应激大鼠认知障碍的发生。VBco的作用可能与其阻抑应激大鼠血浆Hcy水平有关。
Objective To investigate whether compound B vitamins is protective in the course of stress induced cognitive impairment. Methods Male adult SD rats were divided into 5 groups(n=30/group). The experimental group(CUMS) was treated by chronic unpredictable mild stress. The vitamin B intervention group(CUMS+VBco) was given compound vitamin B intragastrically during the CUMS process. The vitamin B control group(VBco) was given compound vitamin B intragastrically in the normal rats. The high methionine diet group(Met) was fed a special diet containing 1% methionine while the blank control group(Ctrl) did not receive any special treatment. Meanwhile, the behavior was tested by open-filed test, Morris water maze, step-down test and object recognition test. Plasma homocysteine(Hcy) was measured by HPLC. Results The CUMS rats showed worse performance in behavioral tests, while the CUMS+VBco rats were not different from the Ctrl ones. Furthermore, supplementation of compound B vitamins to rats alone showed no beneficial effect on behavioral performance. On the other hand, persistent stress induced the elevation of plasma Hcy level in rats, which could be reversed by the intake of B vitamins. The high methionine diet also increased the Hcy in plasma and decreased the performance in behavioral tests. Conclusion Chronic stress can induce cognitive dysfunction in rats, and compound B vitamins can effectively alleviate cognitive impairment in stressed rats. The effect of compound B vitamins is partially related to the decrease of plasma Hcy levels in stressed rats.
Objective To investigate whether compound B vitamins is protective in the course of stress induced cognitive impairment. Methods Male adult SD rats were divided into 5 groups(n=30/group). The experimental group(CUMS) was treated by chronic unpredictable mild stress. The vitamin B intervention group(CUMS+VBco) was given compound vitamin B intragastrically during the CUMS process. The vitamin B control group(VBco) was given compound vitamin B intragastrically in the normal rats. The high methionine diet group(Met) was fed a special diet containing 1% methionine while the blank control group(Ctrl) did not receive any special treatment. Meanwhile, the behavior was tested by open-filed test, Morris water maze, step-down test and object recognition test. Plasma homocysteine(Hcy) was measured by HPLC. Results The CUMS rats showed worse performance in behavioral tests, while the CUMS+VBco rats were not different from the Ctrl ones. Furthermore, supplementation of compound B vitamins to rats alone showed no beneficial effect on behavioral performance. On the other hand, persistent stress induced the elevation of plasma Hcy level in rats, which could be reversed by the intake of B vitamins. The high methionine diet also increased the Hcy in plasma and decreased the performance in behavioral tests. Conclusion Chronic stress can induce cognitive dysfunction in rats, and compound B vitamins can effectively alleviate cognitive impairment in stressed rats. The effect of compound B vitamins is partially related to the decrease of plasma Hcy levels in stressed rats.
引文
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[12]弓景波,王新兴,杲修杰,等.应激对同型半胱氨酸关键代谢酶活性的影响[J].营养学报,2013,35:246-249.
[13]Zhao Y,Qian LJ.Homocysteine-mediated intestinal epithelial barrier dysfunction in the rat model of irritable bowel syndrome caused by maternal separation[J].Acta Biochim Biophys Sin,2014,46:917-919.
[14]张全鹏,王慧,陈旦,等.水合氯醛、乌拉坦及其1:1混合液在SD大鼠麻醉中的效果比较及应用[J].现代生物医学进展,2011,11:1208-1212.
[15]胥达,钱令嘉.高压液相荧光检测法检测血浆同型半胱氨酸[J].中国应用生理学杂志,2005:353-355.
[16]Sehadri S,Beiser A,Selhub J,et al.Plasma homocysteine as a risk factor for mentia and Alzheimer’s disease[J].N Engl J Med,2002,346:476-478.
[17]Budge M,Johnston C,Hogervorst E,et al.Plasma total homocysteine and congnitive performance in a volunteer elderly population[J].Ann NY Acad Sci,2000,903:407-410.
[18]胡尧,郭启浩,岑屹,等.老年痴呆患者认知功能与维生素B12及叶酸的相关性[J].检验医学,2017,32:284-289.
[2]de Kloet ER,Joёls M,Holsboer F.Stress and the brain:from adaptation to disease[J].Nat Rev Neurosci,2005,6:463-475.
[3]Joels M,Baram TZ.The neuro-symphony of stress[J].Nat Rev Neurosci,2009,10:459-466.
[4]Lucassen PJ,Pruessner J,Sousa N,et al.Neuropathology of stress[J].Acta Neuropathol,2014,127:109-135.
[5]Kario K.Measuring the effects of stress on the cardiovascular system during a disaster:the effective use of self-measured blood pressure monitoring[J].J Hypertension,2010,28:657-659.
[6]Ricci S,Fuso A,Ippoliti F,et al.Stress-induced cytokines and neuronal dysfunction in Alzheimer's disease[J].J Alzheimers Dis,2012,28:11-24.
[7]Mc Ewen BS,Bowles NP,Gray JD,et al.Mechanisms of stress in the brain[J].Nat Neurosci,2015,18:1353-1363.
[8]Ottens TH,Dieleman JM,Sauёr AM,et al.Effects of dexamethasone on cognitive decline after cardiac surgery:a randomized clinical trial[J].Anesthesiology,2014,121:492-500.
[9]Kim H,Kim G,Jang W,et al.Association between intake of B vitamins and cognitive function in elderly Koreans with cognitive impairment[J].Nutr J,2014,13:118.
[10]卢晓航,黄晓新.叶酸和维生素B12添加治疗糖尿病合并脑梗死患者认知功能障碍的临床研究[J].中国临床神经科学,2010,18:530-533.
[11]李舟.叶酸片、甲钴胺片及维生素B6片治疗血管性认知功能障碍的疗效分析[J].中国实用神经疾病杂志,2016,19:126-127.
[12]弓景波,王新兴,杲修杰,等.应激对同型半胱氨酸关键代谢酶活性的影响[J].营养学报,2013,35:246-249.
[13]Zhao Y,Qian LJ.Homocysteine-mediated intestinal epithelial barrier dysfunction in the rat model of irritable bowel syndrome caused by maternal separation[J].Acta Biochim Biophys Sin,2014,46:917-919.
[14]张全鹏,王慧,陈旦,等.水合氯醛、乌拉坦及其1:1混合液在SD大鼠麻醉中的效果比较及应用[J].现代生物医学进展,2011,11:1208-1212.
[15]胥达,钱令嘉.高压液相荧光检测法检测血浆同型半胱氨酸[J].中国应用生理学杂志,2005:353-355.
[16]Sehadri S,Beiser A,Selhub J,et al.Plasma homocysteine as a risk factor for mentia and Alzheimer’s disease[J].N Engl J Med,2002,346:476-478.
[17]Budge M,Johnston C,Hogervorst E,et al.Plasma total homocysteine and congnitive performance in a volunteer elderly population[J].Ann NY Acad Sci,2000,903:407-410.
[18]胡尧,郭启浩,岑屹,等.老年痴呆患者认知功能与维生素B12及叶酸的相关性[J].检验医学,2017,32:284-289.