淫羊藿总黄酮的抗缺氧药理作用及机制研究
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摘要
目的
     筛选淫羊藿中具有抗缺氧作用的活性部位,研究其抗缺氧药理作用和机制。
     方法
     1.采用常压密闭缺氧小鼠模型,从淫羊藿水提物、淫羊藿醇提物和淫羊藿总黄酮中筛选淫羊藿中抗缺氧活性部位,再利用急性减压缺氧模型和免疫抑制模型,研究其抗缺氧药理作用。
     2.研究淫羊藿抗缺氧活性部位抗缺氧的药理作用机制。采用减压缺氧小鼠模型,清洁级雄性BALB/C小鼠随机分为:正常对照组,HYM组,药物低、中、高组和阳性药对照组,正常对照组和HYM组均给予等体积蒸馏水,药物组的给药剂量分别为300mg·kg~(-1)·d~(-1)、600 mg·kg~(-1)·d~(-1)和900 mg·kg~(-1)·d~(-1),以上均为灌胃(i.g.)给药。分别从心、脑、肺组织的保护作用,糖代谢,神经内分泌系统等方面研究药理作用机制,所选指标包括:缺氧小鼠的存活时间,大脑、心肌和肺的含水量,大脑和心肌的SOD活性、MDA含量和乳酸含量,肝糖原、肌糖原,肝脏G-6-Pase活性和GK活性,血浆皮质酮、雌二醇和睾酮的含量,外周血象指标和脏器指数,制作大脑、心肌、肾上腺和睾丸组织的病理切片,观察病理变化。
     结果
     1.淫羊藿水提物能明显延长缺氧小鼠的存活时间。对淫羊藿的水提物、醇提物和总黄酮的药效对比时,淫羊藿总黄酮(TFE)能显著延长缺氧小鼠的存活时间(P<0.05)。在做TFE抗缺氧量效关系实验时,给药剂量为900 mg·kg~(-1)·d~(-1)的高剂量组的缺氧小鼠存活时间最长;从外周血象的指标来看,TFE能使缺氧小鼠的血红细胞数量和血红蛋白含量增加,说明淫羊藿总黄酮能改善缺氧小鼠的血液成分,提高缺氧小鼠的血液携氧能力;TFE能使血白细胞和淋巴细胞的数量增加,说明淫羊藿总黄酮能提高缺氧小鼠免疫功能。给药剂量为900 mg·kg~(-1)·d~(-1)的TFE高剂量组的效果最好。
     2.TFE能使缺氧小鼠心、脑SOD活性升高,MDA含量下降,乳酸含量下降;脑、心肌和肺含水量的降低。病理学实验结果也表明TFE能够保护缺氧时心、脑组织的细胞结构,减轻细胞水肿。药效最佳的给药剂量为900 mg·kg~(-1)。
     3.TFE可显著升高缺氧时小鼠空腹血糖,可使肝糖原水平降低,G-6-Pase活性升高,GK活性降低,脑、心肌蛋白质含量升高。
     4.在神经内分泌方面,TFE可抑制应激状态下HPA轴的功能,显著降低血浆CORT的含量,肾上腺指数提高,病理实验结果也表明TFE能保护缺氧小鼠的肾上腺组织。TFE可以发挥性激素样作用,调节HPG轴功能,血浆睾酮、雌二醇含量降低,病理学实验结果也表明TFE能保护缺氧小鼠的睾丸组织。药效最佳的给药剂量为900 mg·kg~(-1)。
     5.在免疫系统方面,TFE能升高CTX致免疫抑制小鼠的免疫器官指数和外周血白细胞和淋巴细胞数目。药效最佳的给药剂量为900 mg·kg~(-1)。
     结论
     1.淫羊藿具有良好的抗缺氧作用。
     2.淫羊藿抗缺氧小鼠缺氧应激的主要药效部位是淫羊藿总黄酮,并发现在药物有效的、合理的使用范围内,给药剂量与药效呈线性关系。
     3.淫羊藿总黄酮抗缺氧机制可能包括:改善缺氧小鼠的心、脑自由基代谢,改善缺氧小鼠心肌、大脑和肺脏的水盐代谢,对心、脑和肺起到保护作用;改善缺氧时的物质代谢水平,以糖代谢为主,减缓蛋白质代谢,保证重要脏器的能量供应,这可能是其对急性缺氧时小鼠心、脑和肺脏组织起保护作用的物质代谢基础。
     4.淫羊藿总黄酮对缺氧状态下激活的HPA轴显示了一定的抑制作用;TFE能发挥性激素样作用,对缺氧状态下的HPG轴具有调节作用;同时对CTX致免疫抑制小鼠体液免疫有较强的改善作用。这说明淫羊藿总黄酮可能通过神经内分泌免疫网络调节机制减轻缺氧造成的损伤。
     5.淫羊藿总黄酮对体液免疫及非特异性免疫功能有较强的改善作用。
Objective:
     To screen the anti-hypoxia active components of Epimedium Herb(HE),study the anti-hypoxia pharmacological effect and explore its mechanisms.
     Methods:
     The anti-hypoxia active component of Epimedium Herb was screened by the closed anoxic model under the condition of ordinary.The mechanisms of its effect were studied by the low pressure and immunization models in mice,respectively.
     The mechanism of the active components of HE was investigated by the acute anoxic model under the low pressure conditions similar to the plateau hypoxia environment in BALB/C mice,and according to the purpose of the experiment,the mice were divided into four groups,i.e.normal control group,HYM group,drug-treated group and positive control group.All drugs were administered by intragastric administration(i.g.).
     The mechanism of the active components of HE was systematically evaluated by determining the following indicators.The content of water in cerebral,myocardium and lung tissues;SOD activity,lactic acid,malondialdehyde(MDA) and protein content in both cerebral and cardiac tissues;liver glycogen and muscle glycogen contents,GK and G-6-P activities in liver;levels of plasmatic corticosterone,plasma glucose level and plasmatic testosterone,estradiol peripheral hemogram and organ index;pathological sections of cerebral, myocardium,adrenal and testis tissues.
     The mechanism of the active components of HE was also studied by the protective effects on heart,brain and lung,the regulatory effects on glucose and protein metabolism,and the improving effects on nerve-endocrine-immune system.
     Results:
     The survival time of mice under ordinary pressure was longer in aqueous extracts of Epimedium Herb treated groups than that of blank control group(P<0.05).TFE had a similar effect on increasing the survival time of mice than that of aqueous and alcohol extracts of HE. The mice treated with the high-dose of TFE(900 mg·kg~-(1)·d~-(1)) displayed the longest survival time.The treatment of TFE significantly increased the contents of red blood cell,white blood cell and lymphocytes,and the hemoglobin content as well.In the dose-effect relationship study of TFE anti-hypoxia,high-dose of TFE(900 mg·kg~(-1)·d~(-1)) showed the most significantly increasing effects.
     After the administration of TFE,SOD activity increased,while MDA and lactic acid content decreased in cerebral and cardiac muscle tissue.
     Meanwhile,plasma glucose level,the liver G-6-Pase activity and protein content in both cerebral tissue and cardiac tissue increased,while liver glycogen content,GK activity and the content of water in cerebral tissue,myocardium and lung tissue decreased when the mice were exposed to hypoxia.The pathological study proved that there was some damage in cerebral and cardiac muscle tissue,which was protected by the treatment of TFE in hypoxia mice.
     Compared with hypoxia model group,after the administration of TFE,the function of HPA axis was inhibited,the level of plasma corticosterone decreased and organ index of adrenal increased in hypoxia stress mice.The pathological study proved that there was some damage in adrenal tissue,which had been protected by the treatment of TFE in hypoxia stress mice.
     TFE was also proved to have the effect similar to sex hormone.After the administration of TFE,the function of HPA axis was regulated,the content of plasma estrogen and testosterone increased.The pathological study also demonstrated that testis tissue was damaged while protected by treatment of TFE in hypoxia stress mice.
     Compared with hypoxia model group,TFE increased immune organ index,leukocyte and lymphocyte numbers of immunosuppressive mice induced by cyclophosphamide.
     High-dose ofTFE(900mg·kg~(-1)·d~(-1)) had the best anti-hypoxia stress effect among the three groups.
     Conclusion:
     Epimedium Herb has significant anti-hypoxia pharmacological effect.
     TFE is the active components of Epimedium Herb in the antihypoxia effect.On the reasonable range of dosage,it showed linear dose-effect relationship.
     TFE can improve the metabolism of free radical,water and salt content in cerebral and cardiac muscle tissues.It can also reduce edema degree,and thus plays an important role in the protection for cerebral,cardiac and lung in hypoxia mice.TFE can also regulate the metabolism of substance,increase the speed of glucose metabolism,slow down protein metabolism and increase the fasting blood glucose level to supply energy to critical organ protecting the heart and brain of hypoxia mice.
     TFE had inhibitory effect on HPA axis of hypoxia mice.It acted as a sex hormone for the regulation of HPG axis function and could improve the immune function of immunosuppressive mice induced by cyclophosphamide,suggesting that TFE reduced injury ofhypoxia mice by the mechanism of NIM.
     TFE can improve blood component,increase the oxygen-carry ability of blood,the number of white blood cell and lymphocyte cell and the immunological competence in hypoxia stress mice.Hence,TFE effectively improve the functions of humoral immunity and nonspecific immuuity.
引文
[2]王婷,张金超,陈瑶,等.6种淫羊藿黄酮抗氧化和抗肿瘤活性的比较[J].中国中药杂志,2007,32(8):715-718.
    [3]谢娟平,孙文基.淫羊藿属植物化学成分及药理研究进展[J].海峡药学,2006,18(5):17-20.
    [4]张有志,聂惠民,胡愉,等.柴地合方对慢性应激抑郁模型大鼠免疫功能的影响[J].中国中医基础医学杂志,2004,10(9):683-686.
    [5]罗昭华,唐彦萍,袁谨,等.淫羊藿苷对巨噬细胞iNOS和TNF-α mRNA的影响[J].遵义医学院学报,2005,28(5):409-411.
    [6]郝炳华,陶明,何立端,等.淫羊藿总黄酮对荷瘤小鼠细胞免疫及红细胞免疫功能的影响[J].西安医科大学报,1999,20(3)323-325.
    [7]熊平源,郭凯文,唐朝辉,等.淫羊藿对小鼠免疫功能的调节作用[J].数理医药学杂志,2007,20(1):50-52.
    [8]丁雁,邢善田,周金黄.淫羊藿多糖促进小鼠T和B细胞~3H-TdR掺入和诱生干扰素作用的研究[J].中国免疫学志,1985,1(6):42.
    [9]孙奕,王景明,骆永珍.淫羊藿总黄酮促进免疫功能低下小鼠IL-2和NK活性的实验研究[J].中草药,2002,33(7):635-637.
    [10]李晓燕,张玲,王芸,等.淫羊藿苷逆转转化生长因子β_2对LAK、CD_3AK细胞的免疫抑制作用[J].中国免疫学杂志,2000,16(5):266-270.
    [11]汪年松,唐令诠,竺艳娟,等.淫羊藿对血液透析HCV感染者细胞免疫功能的作用[J].上海免疫学杂志,2001,21(2):115-116.
    [12]苗起芬,马俐儒,赵春华,等.淫羊藿对慢性肾盂肾炎患者血清白介素6、白介素8的影响[J].中国老年学杂志,2005,25:1177-1178.
    [13]David B,Karo G D,Monte et al.Involvement of rel/nuclear factor κB transcripti NF-κB on factors in keratinocyte senescence[J].Cancer Research,2004;64(2):472-481.
    [14]Karin M,Lin A.NF-kappa B at the crossroads of life and death[J].Nat Immunol,2002,3(3):221-7.
    [15]刘小雨,沈自尹,黄建华,等.淫羊藿总黄酮经由核因子-κB相关信号转导途径调控免疫衰老机制[J].中国中西医结合杂志,2006,26(7)620-624.
    [16]陈玮,邹焰,姜东.人参、淫羊藿增强小鼠免疫功能的协同作用[J].遵义医学院学报,2001,24(2):124-125.
    [17]Niu P,Shindo T,Iwata H,et al.Protective effect of adrenomedullin in heart failure[J].circulation,2004,109(14):1789-94.
    [18]Sun HY,Wang NP,Kerendi F,et al.Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca~(2+) overload[J].Am J Physiol Heart Circ physiol,2005,288(4):1900-1908.
    [19]潘志伟,王秋娟,柳仁民,等.淫羊藿苷预适应对乳鼠心肌细胞的保护作用[J].中国药科大学学报,2007,38(1):73-76.
    [20]尹晓飞,李冬梅,蔡大伟,等.淫羊藿总黄酮对小鼠心肌缺氧的保护作用[J].中国医院药学杂志,2008,28(4):283,284,297
    [21]刘桦,季晖,张超英.淫羊藿苷对异丙肾上腺素所致乳鼠心肌细胞损伤的保护作用[J].中国药理学通报,2006,22(12):1509-1512.
    [22]黄秀兰,王伟,周亚伟.淫羊藿总黄酮注射液对正常麻醉开胸犬血流动力学的影响[J].解放军药学学报,2006,22(1):25-29.
    [23]李梨,石京山,周歧新.淫羊藿苷对缺血/再灌致神经元损伤的保护作用研究[J].四川生理科学杂志,2005,26(4):175.
    [24]沈磊,张鸽,吴玉林.淫羊藿总黄酮对大鼠局灶性脑缺血的保护作用[J].中药新药与临床药理,2007,18(4):266-269.
    [25]付立波,夏映红,于丽,等.淫羊藿总黄酮对大鼠动脉血压影响及其机制的实验研究[J].中国应用生理学杂志,2007,23(1):115-116.
    [26]吉瑞瑞,李付英,张雪静,等.淫羊藿苷对缺氧诱导血管内皮细胞损伤的保护作用[J].中国中西医结合杂志,2005,25(6):525-530.
    [27]李朝阳,石进校,粟银,等.箭叶淫羊藿叶醇提物对自由基的清除作用[J].华中科技大学学报,2003,31(9):105-107.
    [28]朱芮,邹典定.川芎嗪对新生儿缺血缺氧性脑病一氧化氮及氧自由基的影响[J].中国中西医结合杂志,2005,25(8):737.
    [29]包名家,周维民,王建萍,等.淫羊藿对D-半乳糖诱导的衰老小鼠大脑皮层一氧化氮的影响[J].中国老年学杂志,2005,25:460-461.
    [30]黄秀兰,王伟,张雪静,等.淫羊藿总黄酮注射液对H_2O_2诱导心肌细胞损伤的影响[J].北京中医药大学学报,2006,29(6):404-407.
    [31]Gonzalo A.Carrasco,Louis D.Van de Kar~*,Neuroendocrine pharmacology of stress[J], European Journal of Pharmacology,2003,(463):235-272.
    [32]蒋淑君,王桂兰,崔存德,等。淫羊藿总黄酮对肾阳虚大鼠下丘脑—垂体—肾上腺轴钙调蛋白基因表达的影响[J].中国应用生理学杂志,2004,20(4):341,353.
    [33]沈自尹,陈瑜,淫羊藿总黄酮与补肾复方对皮质酮大鼠T细胞凋亡相关基因群调控的对比研究[J].中国免疫学杂志,2002,18:187-190.
    [34]ShaarawyM,Abassi AF,Hassan H,et al.Relationship between serumleptin concentrations and bone mineral density as well as biochemical markers of bone turnover in women with postmenopausal osteoporosis[J].Fertil Steril,2003,79(4):919-924.
    [35]雪原,齐清会,王沛,等.淫羊藿苷对OVX大鼠成骨细胞Smad4 mRNA的作用[J].天津医药,2006,34(4):256-258.
    [36]李丽,王超,张静.缺氧性呼吸抑制的中枢机制[J].医学综述,2007,13(17):1341-1343
    [37]龙超良,周智,尹照云,等.慢性缺氧对大鼠心功能的影响[J].航天医学与医学工程,1999,12(4):266-269.
    [38]刘辉,刘勇,贾庆军,等.急性高原缺氧对大鼠心脏信号传导系统的影响[J].临床军医杂志,2003,31(5):8-10.
    [39]梁丽娟,熊开宇,田野,等.间歇性低氧暴露期间运动对体育系大学生脑血流速度的影响[J].中国运动医学杂志,2005,24(1):76-80.
    [40]钱金桥,杨炎华,周定邦,等.缺氧性肺血管收缩的细胞机制[J].医学综述,2005,11(4):307-309
    [41]罗炎杰.氧离曲线偏移的判断及其临床应用[J].四川医学,1998,19(6):513-514
    [42]姜北芳,刘威.缺氧状态下神经系统的改变和护理[J].中国实用医药,2008,3(25):183-4
    [43]阴健,郭力弓.中药现代研究与临床应用[M].第1版,北京:学苑出版社,1993:646-652
    [1]罗军德,张汝学,贾正平,等.锁阳抗缺氧活性部位的药理作用及机制研究[J].中药新药与临床药理,2007,18(4):275-279
    [2]杨梅,格日力,周晓梅,等.藏药抗缺氧作用的初步研究[J].中国中药杂志.2004,29(11):1117-1118
    [3]Lipton SA.Rosenberg PA.Excitatory amino acids as a final common pathway for neurologic disorders[J].N Engl J Med,1994,330(9):613-622
    [4]王辉,周立,刘刚.莲心碱对氧自由基引发红细胞膜损伤的保护作用[J].中国药理学通报,2006,22(9):1088-1091
    [5]张翠萍,何艳,谢印芝.低氧对免疫功能的影响及其机制[J].高原医学杂志,2001,11(4):52-57
    [6]胡宗海,胡娟.高原环境对机体免疫功能的影响机制[J].西北国防医学杂志,2004,25(2):130-132
    [1]王镜岩,朱圣庚,徐长法主编.生物化学(下册)[M].见:王镜岩.糖酵解作用,第3版,北京:高等教育出版社,2002:81-82
    [2]陈强,郭修武,胡艳丽,等.淹水对甜樱桃根系呼吸和糖酵解末端产物的影响[J].园艺学报,2008,35(2):169-174
    [3]宋秀荣,刘仁光.苯那普利对乳鼠心肌细胞缺氧复氧自由基损伤的保护作用[J].中国心 血管病研究杂志,2006,4(3)205-207
    [4]宋红梅,冯加纯.脑缺血的自由基损伤机制与神经保护研究[J].中国卒中杂志,2006,9:635-638
    [5]臧秀贤,董均树,李秀江.氧自由基在急性期多器官功能障碍综合征心肌损伤中的变化[J].中华急诊医学杂志,2006,15(2):128-130
    [6]张钢,高钰琪,刘福玉.缺氧大鼠白细胞流变学特性和整合素CD18表达的变化[J].解放军医学杂志[J],2008,33(1):69-71
    [7]Schurr A.Energy metabolism,stress hormones and neural recovery from cerebral ischemia /hypoxia[J].Neurochem Int,2002,41(1):1-8
    [8]Ruiz-Gines JA,Lopez-Ongil S,Gonzalez-Rubio M,et al.Reactive oxygen species induce proliferation of bovine aortic endothelial cells[J].J Cardiovasc Pharmacol,2000,35:109-113.
    [9]魏登邦,张宝琛.缺氧引起的自由基增殖及其损伤[J].生物学通报,2003,38(1):7-10
    [10]吴俭,金国强,赵玲.缺氧缺血新生大鼠脑组织SOD、MDA和NO的变化及硫酸镁的保护作用[J].江西医学院学报,2002,42(1):49-52.
    [1]母得志.缺氧缺血与脑水肿.中华妇幼临床医学杂志[J],2006,2(4):181-183
    [2]Boulard G.Plasma osmolarity and cerebral volume[J].Ann Fr Anesth Reanim,2001,20(2):196-202
    [3]戚晓红,余卫平.病理生理学[M].见:庞庆丰.缺氧,第1版,北京:科学出版社,2001:65-75
    [4]郭文超,易咏红,陈盛强,等.拉莫三嗪治疗新生大鼠缺氧缺血性脑水肿的实验研究[J].临 床与实验医学杂志,2006,5(2):103-104
    [5]朱华玲,汪海.埃他卡林对急性低压缺氧所致大鼠脑水肿的预防作用[J].航天医学与医学工程,2006,19(4):287-291
    [6]张伟,张昱.不同海拔地区小鼠氧自由基的改变[J].青海医学院学报,2004,25(3):178-179
    [7]赵贵锋,葛德元.高原肺水肿研究进展[J].心血管病学进展,2008,29(5):757-760
    [8]石增立,李著华.病理生理学[M].见:邹平,王蔚琛.缺氧,第1版,北京:科学出版社,2006:43
    [1]李玉林主编.病理学[M].见:唐建武.细胞和组织的适应与损伤,第6版,北京:人民卫生出版社,2004:8-9
    [2]姜振宇,郝克清,尚贵民,等.氧自由基与心肌损伤[J],心血管康复医学杂志,2001,10(1):82-85
    [3]Court O,Kumar A,Parrillo JE,et al.Clinical review:Myocardial depression in sepsis and septic shock[J].Crit Care,2002,6(6):500-508.
    [4]朱静峰,黄冬.氧自由基、钙超载与心肌缺血再灌注损伤[J].云南医药,2007,28(1):67-70
    [5]章培军,吕永利,赖红,等.氧自由基损伤海马神经元及人参皂苷的保护作用[J].解剖科学进展[J],2000,6(3):264-266
    [6]许雾虹,王俊科,袁治国,等.骨形态发生蛋白-7基因转染对新生大鼠心肌细胞缺氧-复氧时凋亡的影响[J].中华麻醉学杂志,2007,27(12):1114-1117
    [7]王显刚,殷惠军,史大卓.蒺藜总皂苷对缺氧复氧心肌细胞存活及损伤形态的影响.解放军医学杂志[J],2006,31(6):528-530
    [1]王镜岩,朱圣庚,徐长法主编.生物化学(下册)[M].见:文重,王镜岩.脂肪酸的分解代谢,第3版,北京:高等教育出版社,2002:232-247
    [2]王镜岩,朱圣庚,徐长法主编.生物化学(下册)[M].见:王镜岩,文重.蛋白质降解和氨基酸的分解代谢,第3版,北京:高等教育出版社,2002:301
    [3]王镜岩,朱圣庚,徐长法主编.生物化学(下册)[M].见:王镜岩.糖酵解的作用,第3版,北京:高等教育出版社,2002:74-80
    [4]徐叔云,卞如濂,陈修.药理实验方法学[M].第2版.北京:人民卫生出版社,1994:1246-1260
    [5]Van hoof KD Schrijver,R.Effect of unprocessed and baked inulin on lipid metabolism in normal and hyper-cholesterolemic rats[J].NutrRes,1995,15(11):1637-1639
    [6]Baginski ES,Foa PP and Zad B.Methods in enzymatic analysis[J].New York and London:Academic Press,1974:876
    [7]T Nishio,Y Toyoda,M Hiramatsu,et al.Decline in glucokinase activity in the arcuate nucleus of streptozotocin-induced diabetic rats[J].Biol Pharm Bull,2006,29(2):216-219.
    [8]吴天一.高原医学的黄金时代[J].高原医学杂志,1997,7(2):1.
    [9]张广钦,陈世忠,郝雪梅,等.厚朴酚对脑缺血的保护作用[J].中国药理学通报,2003,19(9):1020-1023.
    [10]Fiordaliso F,Bianchi R,Staszewsky L,et al.Antioxidant treatment attenuates hypergly-cemia-induced cardiomyocyte death in rats[J].J Mol Cell Cardiol,2004,37(5): 959-968.
    [11]Yukitaka Shizukuda,Reyland ME,Buttrick PM.Protein kinase C-modulates apoptosis induced by hyperglycemia in adult ventricular myocytes[J].Am J Physiol Heart Circ Physiol,2002,282(5):H1 625-634
    [12]Malhotra A,Kang BP,Hashmi S,et al.PKC epsilon inhibits the hyperglyce-mia-induced apoptosis signal in adult rat ventricular myocytes[J].Mol Cell Biochem,2005,268(1-2):169-173.
    [13]Schaffer SW,CroftCB,SolodushkoV.Cardioprotective effectof chronic hyper-glycemia:effect on hypoxia-induced apoptosis and necrosis[J].Am JPhysiol Heart Circ Physiol,2000,278(6):H1 948-954
    [14]Schurr A,Payne RS,Miller JJ,et al.Preischemic hy-perglycemia aggravated damage:evidence that lactateutilization is beneficial and glucose induced corticos-terone release is detrimental[J].J Neurosci Res,2001,66(5):782-789.
    [15]王艳梅,叶柳辉,张华才,等.葡萄糖对缺氧耐受性影响实验研究[J].中国科技信息,2007,11:199,208
    [16]孙颖,刘德敏,赵慧茹,等.栎精对葡萄糖-6-磷酸酶基因表达及活性的影响[J].天津医药,2007,35(12):918-920
    [17]邱文娟,张雅芬,潘骏,等.葡萄糖6磷酸酶基因热点突变检测结合1176多态位点连锁分析快速产前诊断Ⅰa型糖原累积病[J].中华医学遗传学杂志,2005,22(1):44-48
    [18]沈云峰,翁建平.葡萄糖激酶基因突变与功能学研究进展[J].国际内科学杂志,2008,35(12):692-695
    [1]谢永宏,金发光,钱桂生.急性高山病及高原脑水肿研究进展[J].国外医学医学地理分册,2004,25(3):105-108
    [2]吴雁,杜继曾.低氧暴露条件下高原鼠兔和大鼠HPA轴活动的比较[J].兽类学报,2001,21(3):195-198
    [3]田怀军.高原低氧环境对生殖内分泌的影响[J].解放军医学杂志,2005,30(5):449-450
    [4]胡宗海,胡娟.高原环境对机体免疫功能的影响机制[J].西北国防医学杂志,2004,25(2):130-132
    [5]赵旦,王坚,李洁,等.焦虑状态、高强度运动下大鼠神经肽Y和下丘脑-垂体-肾上腺轴的相互影响[J].医学研究生学报,2008,21(9):929-932
    [6]程传苗,李兆申,黄文,等.军事应激对军人心理和免疫内分泌系统的影响[J].解放军医学杂志,2007,32(3):189-190
    [7]Khansari DH,Dantzer R,Kelly KW,et al.Effect of stress on the immune system[J].Immunol Today,1990,11(5):170
    [8]杨叔.下丘脑-垂体-肾上腺皮质轴应激反应的中枢控制[J].生理科学进展,2000,31(3):222-226
    [9]吴雁,杜继曾.低氧暴露对大鼠下丘脑CRF分泌的影响[J].中国应用生理学杂志,2001;17(4):317-319
    [10]吕永达.高原医学与生理学[M].见:罗德成.高原低氧对内分泌系统的影响,第1版,天津:天津科技翻译出版公司,1995:170
    [1]蒋春雷,路长林.应激医学[M].第1版,上海:上海科学技术出版社,2006:340
    [2]金惠铭,王建枝.病理生理学[M].见:王树人.应激,第6版,北京:人民卫生出版社,2004:156
    [3]吕永达.高原医学与生理学[M].见:罗德成.高原低氧对内分泌系统的影响,第1版,天津:天津科技翻译出版公司,1995:184-185
    [4]Okumura A,Fuse H,Kawauchi Y,et al.Changes in male reproductive function after high altitude mountaineering[J].High AltMed Boil,2003,4(3):349-353
    [5]Farias JG,Bustos Obregon E,OrellsanaR,et al.Effects off chronic hypobaric hypoxia on testis histology and round spermatid oxidative metabolism[J].Androiogra,2005,37(1):47-52
    [6]林丹曦,张建平.肺源性心脏病患者血浆睾丸酮含量测定及其意义[J].临床内科杂志,1997,14(3):160
    [7]姚泰.生理学[M].见:李玉荣.生殖,第6版,北京:人民卫生出版社,2004:383-388
    [8]侯林,徐会茹,王晨阳,等.恐惧应激对雄性大鼠生殖激素的影响[J].医学研究生学 报,2007,20(9):920-922
    [9]Eliakim A,NemetD.Exercise and the male reproductive system[J].Harefuah,2006,145(9):677-681.
    [10]李素芝,蔡志祥,王洪斌,等.高原低氧对女性孕酮、雌二醇的影响[J].放射免疫学杂志,2006,19(1):30-31
    [11]程海萍,王秀娟.高原低氧环境下大鼠睾丸酮水平变化[J].青海医学院学报,2008,29(2):123-125
    [1]孙奕,王景明,骆永珍.淫羊藿总黄酮促进免疫功能低下小鼠IL-2和NK活性的实验研究[J].中草药,2002,33(7):635-637
    [2]沈自尹,吴志军,于立华,等.淫羊藿总黄酮对皮质酮诱导免疫功能低下大鼠的保护作用及配伍研究[J].中国药理学通报,2007,23(8):1061-1063
    [3]李业鹏,计融,韩春卉,等.建立小鼠免疫低下模型的初步研究[J].中国食品卫生杂志,2001,13(6):7-10
    [4]罗军德.锁阳抗缺氧活性部位的药理作用及机制研究[D].硕士学位论文,兰州:兰州大学,2007.5:41
    [5]刘斌,米粲,卞修武.环磷酰胺对人腺泡状横纹肌肉瘤细胞裸鼠移植瘤生长和形态结构的影响[J].第三军医大学学报,2007,29(1):74-77.

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