气滞血瘀证动物模型研究现状
|
摘要
气滞血瘀证是临床常见证型,它的形成与饮食、情绪、环境等因素有关。随着现代人们生活节奏的加快和生活压力的加大,情志不舒在所难免,再加上饮食油腻等方面的原因,很容易引发气滞血瘀型疾病。临床研究和治疗大都停留在外部宏观手段和技术上,很难对证型发展的微观改变及证型演变规律进行深入系统的了解,这就需要制作和临床发病机制相关的动物模型。为了了解近些年气滞血瘀证及病证结合动物模型研究的现状,本文就造模方法、检测指标及造模原理等方面进行综述。气滞血瘀证常见的造模方法有肾上腺素法、右旋糖酐法、声光电复合刺激法、束缚法、夹尾法、高脂寒凝法、睡眠剥夺法等。模型成功与否的验证指标主要为血液流变学指标,其次还有旷场试验、微循环、体重、神经递质、血管内皮因子等方面的检测。常见的气滞血瘀证病证结合模型有子宫内膜异位症气滞血瘀证模型、气滞血瘀证妇科疾病特点模型、糖尿病气滞血瘀证模型、非小细胞肺癌气滞血瘀证模型、气滞血瘀型慢性非细菌性前列腺炎等。不同的造模方法应用不同,本文通过将近些年造模方式、原理、检测指标进行汇总,为规范气滞血瘀证动物模型提供基础。
Syndrome of blood stasis with Qi stagnation is a common clinical syndrome and the formation is closely related to the diet,mood,environment and other factors. With the quickening pace of modern life and the increasing pressures of life,emotional discomfort is inevitable. In addition,greasy diet and other factors are easy to cause Qi stagnation and blood stasis diseases. Clinical research and treatment most stay in the external macro-means and technology,so it is difficult to understand systematically and deeply about the microcosmic changes of syndrome development and the rule of syndrome evolution. This needs to establish animal models that are related to the clinical pathogenesis. In order to understand the research status about animal models of Qi stagnation and blood stasis syndrome and disease-syndrome combination,the modeling methods,model validation and principles were reviewed in this paper. The common modeling methods of Qi stagnation and blood stasis syndrome include adrenaline method,dextran method,acousto-optic complex stimulation,binding method,clipping tail method,high fat plus cold coagulation,sleep deprivation and so on. The hemorheology indexes are the leading indicator of model validation,followed by open field test,and microcirculation,weight,neurotransmitter,vascular endothelial factor and other tests. The common disease-syndrome combination models of Qi stagnation and blood stasis syndrome include the models of Qi stagnation and blood stasis syndrome with endometriosis,Qi stagnation and blood stasis syndrome with gynecological disease characteristics,Qi stagnation and blood stasis syndrome with diabetes,Qi stagnation and blood stasis syndrome with non-small cell lung cancer,and Qi stagnation and blood stasis syndrome with chronic non-bacterial prostatitis. Different modeling methods are used in the different applications.We summarized the modeling methods,principles and testing indicators in recent years to standardize the animal model of Qi stagnation blood stasis syndrome.
Syndrome of blood stasis with Qi stagnation is a common clinical syndrome and the formation is closely related to the diet,mood,environment and other factors. With the quickening pace of modern life and the increasing pressures of life,emotional discomfort is inevitable. In addition,greasy diet and other factors are easy to cause Qi stagnation and blood stasis diseases. Clinical research and treatment most stay in the external macro-means and technology,so it is difficult to understand systematically and deeply about the microcosmic changes of syndrome development and the rule of syndrome evolution. This needs to establish animal models that are related to the clinical pathogenesis. In order to understand the research status about animal models of Qi stagnation and blood stasis syndrome and disease-syndrome combination,the modeling methods,model validation and principles were reviewed in this paper. The common modeling methods of Qi stagnation and blood stasis syndrome include adrenaline method,dextran method,acousto-optic complex stimulation,binding method,clipping tail method,high fat plus cold coagulation,sleep deprivation and so on. The hemorheology indexes are the leading indicator of model validation,followed by open field test,and microcirculation,weight,neurotransmitter,vascular endothelial factor and other tests. The common disease-syndrome combination models of Qi stagnation and blood stasis syndrome include the models of Qi stagnation and blood stasis syndrome with endometriosis,Qi stagnation and blood stasis syndrome with gynecological disease characteristics,Qi stagnation and blood stasis syndrome with diabetes,Qi stagnation and blood stasis syndrome with non-small cell lung cancer,and Qi stagnation and blood stasis syndrome with chronic non-bacterial prostatitis. Different modeling methods are used in the different applications.We summarized the modeling methods,principles and testing indicators in recent years to standardize the animal model of Qi stagnation blood stasis syndrome.
引文
[1]任建勋,刘建勋,林成仁,等.冠心病不稳定性心绞痛患者气滞血瘀证和气虚血瘀证的生物学基础比较分析[J].中国中西医结合杂志,2010,30(4):352-356.
[2]王均宁,韩涛,路广林.从《内经》血瘀理论探讨血瘀致病的临床特征[J].北京中医药大学学报,2003,26(2):13-14.
[3]刘剑刚,张红霞,董国菊,等.高脂饲料结合免疫损伤、应激所致高脂血症血瘀模型的实验研究[J].中国中西医结合杂志,2003,23(S1):17-20.
[4]须惠仁,傅湘琦,向丽华,等.肝郁证的动物实验研究——激怒刺激对大白鼠血液流变学的影响[J].中医杂志,1991,32(6):45-48.
[5]成秀梅,杜惠兰,李丹.寒凝血瘀证动物模型的创建[J].中国中医基础医学杂志,2005,11(8):604-605.
[6]任建勋,林成仁,王敏,等.多因素整合建立气滞血瘀证动物模型研究[J].中药药理与临床,2007,23(5):210-211.
[7]宁天一,王婷婷,程嘉艺.气滞血瘀证大鼠H2S/CSE、CBS体系的变化[J].中药药理与临床,2012,30(5):234-237.
[8]高嘉良,陈光,何庆勇,等.治疗气滞血瘀证中成药组方规律分析[J].中国中药杂志,2017,42(1):187-191.
[9]和岚,蒋文跃,毛腾敏.注射肾上腺素模拟“气滞”复制急、慢性血瘀模型初探[J].中国中西医结合杂志,2004,24(3):244-246.
[10]章正祥,曹克刚,王芬,等.皮下注射肾上腺素复制气滞血瘀模型的血流动力学初探[J].天津中医药,2011,28(1):9-11.
[11]王艳,郑国庆,王明杰,等.治风活血法对微循环气滞血瘀模型的影响[J].现代中西医结合杂志,2005,14(13):1689-1691.
[12]刘丽芳,曾群,金蓉鸾,等.中药水蛭各部位提取物对高分子葡聚糖所致大鼠血瘀模型的影响[J].中成药,2003,25(7):589-590.
[13]陈守强.高黏血症动物模型研究进展[J].中国微循环,2003,7(6):395-396.
[14]任宏义,任周新.“气滞血瘀”证动物模型的建立[J].实验动物科学,1994,11(3):29-31.
[15]唐已婷,陈家旭.三种中药复方对慢性束缚应激大鼠下丘脑—垂体—肾上腺轴的调节[J].北京中医药大学学报,2002,25(3):23-26.
[16]钟小兰,吕志平,钱令嘉,等.束缚所致肝郁证动物模型肝组织蛋白质组的差异表达研究[J].中医杂志,2006,47(5):371-373.
[17]金光亮,南睿,郭霞珍.慢性应激肝郁证大鼠模型的建立[J].北京中医药大学学报,2003,26(2):18-21.
[18]金光亮.论情志与情志病因[J].中华中医药杂志,1997,12(3):9-11.
[19]李峰,杨维益,梁嵘,等.从中医学看肝脏调节应激反应的作用[J].北京中医药大学学报,1998,21(1):20-22.
[20]王阶,陈可冀,翁维良,等.血瘀证诊断标准的研究[J].中国中西医结合杂志,1998,18(10):585-587,589.
[21]赵日霞,郭瑾,唐纯志,等.针刺治疗对躁狂模型大鼠行为学及睡眠潜伏期的影响[J].疑难病杂志,2016,15(4):412-415.
[22]宋程程,王志斌,苏斌,等.常用大鼠血瘀证模型的比较研究[J].北京中医药大学学报,2014,37(2):94-98.
[23]侯万儒.胆盐的生理作用[J].生物学通报,1990,35(11):17,21.
[24]王友兰,胡志宇,张凤翔,等.丙基硫氧嘧啶对正常Sprague-Dawley大鼠脂肪代谢的影响[J].中国医学研究与临床,2003,1(12):9-10.
[25]Velagaleti R S,Massaro J,Vasan R S,et al.Relations of lipid concentrations to heart failure incidence:the Framingham Heart Study[J].Circulation,2009,120(23):2345-2351.
[26]Rubinstein J,Pelosi A,Vedre A,et al.Hypercholesterolemia and myocardial function evaluated via tissue doppler imaging[J].Cardiovasc Ultrasound,2009,7(1):56-62.
[27]Martins F,Campos D H S,Pagan L U,et al.High-fat diet promotes cardiac remodeling in an experimental model of obesity[J].Arq Bras Cardiol,2015,105(5):479-486.
[28]Maczewski M,Maczewska J.Hypercholesterolemia exacerbates ventricular remodeling in the rat model of myocardial infarction[J].J Card Fail,2006,12(5):399-405.
[29]苗兰,潘映红,任建勋,等.气滞血瘀证模型大鼠血清蛋白质组学初步研究[J].中国中医基础医学杂志,2008,14(2):106-107.
[30]苗兰,潘映红,任建勋,等.血府逐瘀汤对气滞血瘀证大鼠血清蛋白质组表达的影响[J].中国实验方剂学杂志,2008,14(4):24-28.
[31]周象贤,周萍.七情学说与应激理论之特征比较[J].医学与哲学,2001,22(6):49-50.
[32]袁肇凯,黄献平,范伏元,等.心病气血辨证面色变化特点及面部血管容积图检测分析[J].中医杂志,2001,42(3):173-175.
[33]袁肇凯,杨运高,黄献平.气滞血瘀证与气虚血瘀证面色及面部血流图观察[J].中国中西医结合杂志,1995,15(12):734.
[34]张永杰,黄西园.冠心病气滞气虚血瘀证血液流变学及心功能比较[J].辽宁中医杂志,1996,23(9):394.
[35]胡志希,袁肇凯,顾星,等.基于光电血流容积中医色诊脉诊的研究与对策[J].中西医结合心脑血管病杂志,2006,4(9):782-785.
[36]吴锐,穆松牛,余淑娇.五种血瘀证亚型实验家兔模型的比较研究[J].河南中医,2010,30(2):146-147.
[37]胡文娟,张秉韬,吴锐.5种血瘀证亚型家兔模型球结膜微循环改变的比较[J].中国中西医结合杂志,2013,33(9):1261-1266.
[38]胡文娟,张秉韬,吴锐.气虚血瘀证与气滞血瘀证家兔模型的球结膜微循环改变比较[J].新中医,2013,45(4):168-171.
[39]牛雯颖,张玉昆,武爽,等.气滞血瘀模型大鼠红细胞膜生物学研究[J].中国当代医药,2013,20(14):6-8.
[40]李丽琦.三种血瘀模型红细胞膜生物学差异性及寒冷刺激血瘀模型方证相关实验研究[D].哈尔滨:黑龙江中医药大学,2012.
[41]梁耀月,李佳佳,董世芬,等.3种不同血瘀证动物模型的建立与评价[J].中国药理学通报,2016,32(10):1468-1473.
[42]王婷婷,贾乘,陈宇,等.大鼠气滞血瘀证模型的建立及影响因素分析[J].中国中药杂志,2012,37(11):1629-1633.
[43]王婷婷,贾乘,宁天一,等.两种气滞血瘀证造模方法的比较[J].中华中医药学刊,2013,31(1):157-158.
[44]宁天一,王婷婷,姜静,等.气滞血瘀证大鼠NO/NOS体系的变化[J].世界中医药,2013,8(1):71-73.
[45]宁天一,王婷婷,程嘉艺.气滞血瘀证大鼠H2S/CSE、CBS体系的变化[J].中药药理与临床,2012,28(5):234-237.
[46]赵艳,于昕,时丽丽,等.消栓通络方有效成分组对大鼠急性血瘀模型的影响[J].药学学报,2012,47(5):604-608.
[47]李伟霞,黄美艳,唐于平,等.大鼠急性血瘀模型造模方法的研究与评价[J].中国药理学通报,2011,27(12):1761-1765.
[48]贾丹兵,于淼,李乃民,等.寒凝气滞血瘀证大鼠动物模型的建立及评价[J].中医药信息,2014,31(4):75-77.
[49]秦书芝.三首活血化瘀方药对气滞血瘀模型大鼠红细胞膜生物学指标的研究[D].哈尔滨:黑龙江中医药大学,2014.
[50]赵慧辉,王伟.病证结合证候模型研究基本思路[J].中华中医药杂志,2006,21(12):762-764.
[51]刘丹彤,马小娜,张小勇,等.子宫内膜异位症气滞血瘀证大鼠模型的建立及评价[J].中医药学报,2012,40(2):31-35.
[52]马小娜,刘丹彤,闫军堂,等.两种子宫内膜异位症大鼠模型的血液流变学及单胺类神经递质比较研究[J].中华中医药学刊,2012,30(1):179-181.
[53]李炜,段金廒,刘培,等.采用雌性SD大鼠探索建立适宜于气滞血瘀证妇科疾病特点的模型评价体系[J].中国中药杂志,2013,38(8):1211-1218.
[54]李敬林,王太一,王禄增,等.2型糖尿病证病结合动物模型的研究[J].中国比较医学杂志,2007,17(8):473-475.
[55]陈嘉斌,柴可夫,郑杨,等.三种方法建立糖尿病气滞血瘀证型大鼠模型的对比实验研究[J].浙江中医药大学学报,2013,37(3):234-239.
[56]蒋继宏.2型糖尿病大鼠血瘀气滞模型实验研究[D].沈阳:辽宁中医药大学,2006.
[57]鲁兴隆.肺抑瘤膏治疗非小细胞肺癌气滞血瘀证临床观察与实验研究[D].济南:山东中医药大学,2015.
[58]彭召云,郑心,鲁兴隆.肺抑瘤膏对气滞血瘀质Lewis肺癌小鼠肿瘤生长及VEGF-C表达的影响[J].时珍国医国药,2015,26(12):2895-2896.
[59]吴飞彪,邹练.前列腺汤对大鼠气滞血瘀型慢性前列腺炎的影响[J].中国性科学,2014,23(3):55-57.
[60]陈可冀,宋军.病证结合的临床研究是中西医结合研究的重要模式[J].继续医学教育,2007,8(19):12-15.
[61]李凤文,须惠仁,张问渠,等.肝郁气滞血瘀的临床和实验研究[J].中医杂志,1991,24(10):47-49.
[62]D'Aquila P S,Peana A T,Carboni V,et al.Exploratory behaviour and grooming after repeated restraint and chronic mild stress:effect of desipramine[J].Eur J Pharmacol,2000,399(1):43-47.
[63]Roy M,David N,Cueva M,et al.A study of the involvement of melanin-concentrating hormone receptor 1(MCHR1)in murine models of depression[J].Biol Psychiatry,2007,61(2):174-180.
[64]赵海滨,刘子旺,张秀静.电针肝俞、期门对肝气郁结模型大鼠行为学的影响[J].广州中医药大学学报,2012,29(1):30-33.
[65]Green A D,Barr A M,Galea L A.Role of estradiol withdrawal in‘anhedonic’sucrose consumption:a model of postpartum depression[J].Physiol Behav,2009,97(2):259-265.
[66]包祖晓,赵国平,何贵平,等.肝肾阳虚型抑郁症大鼠模型的建立与评价[J].中华中医药学刊,2015,33(1):42-45.
[67]Kapusta D R,Jones S Y,Dibona G F.Opioids in the systemic hemodynamic and renal responses to stress in spontaneously hypertensive rats[J].Hypertension,1989,13(6 Pt 2):808-816.
[68]Mccubbin J A,Surwit R S,Williams R B,et al.Altered pituitary hormone response to naloxone in hypertension development.[J].Hypertension,1989,14(6):636-644.
[69]Millan M J,Przewocki R,Jerlicz M,et al.Stressinduced release of brain and pituitary beta-endorphin:major role of endorphins in generation of hyperthermia,not analgesia[J].Brain Res,1981,208(2):325-338.
[70]毛海燕,叶林,叶向荣.肝郁证大鼠中枢神经递质变化的观察[J].福建中医药,2002,33(2):17-18.
[71]唐照亮,宋小鸽,袁静,等.艾灸对寒凝血瘀证大鼠活血化瘀作用的实验研究[J].中国中医基础医学杂志,2000,6(4):43-46.
[72]任路,李浩.关于肝郁证动物模型研究现状及存在问题的思考[J].中医药学报,2006,34(4):44-46.
[73]Bousquet W F,Miya T S,Sanchez C.Modification of stress responses in histamine-depleted rats[J].Br J Pharmacol Chemother,1966,27(1):177-184.
[74]Kvetnansky R,Mikulaj L.Adrenal and urinary catecholamines in rats during adaptation to repeated immobilization stress[J].Endocrinology,1970,87(4):738-743.
[75]马如飞.束缚应激加重挤压伤大鼠肠道损伤及内质网应激蛋白的表达变化[D].石家庄:河北医科大学,2016.
[76]李莉,张晓静,刘威,等.儿茶酚胺在束缚应激大鼠肺损伤中的作用[J].河北医科大学学报,2017,38(5):501-505.
[77]刘楠.束缚应激加重挤压伤大鼠孤束核损伤[D].石家庄:河北医科大学,2015.
[78]闫珊珊,窦维华,董少龙,等.血瘀证动物模型的制作及存在问题的探讨[J].中国中医基础医学杂志,2004,10(2):35-37.
[79]陈彦辛.子宫内膜异位症证候分布研究与病证结合动物模型的研制[D].广州:广州中医药大学,2013.
[80]邢建华,翟红莉.中医证候动物模型研究近况[J].中国疗养医学,2007,16(2):68-69.
[81]马小娜.病证结合子宫内膜异位症大鼠模型的建立与评价[D].北京:北京中医药大学,2011.
[82]吕爱平.病证结合动物模型研究:从理论创新到技术挑战[J].中国中西医结合杂志,2013,33(1):6-7.
[83]韦薇,徐凤芹.气滞血瘀证客观化研究进展[J].中西医结合心脑血管病杂志,2011,9(5):608-609.
[84]钱小奇,张敏.中医证诊断的特点、现状和展望[J].湖南中医药导报,2000,6(12):5-6,29.
[2]王均宁,韩涛,路广林.从《内经》血瘀理论探讨血瘀致病的临床特征[J].北京中医药大学学报,2003,26(2):13-14.
[3]刘剑刚,张红霞,董国菊,等.高脂饲料结合免疫损伤、应激所致高脂血症血瘀模型的实验研究[J].中国中西医结合杂志,2003,23(S1):17-20.
[4]须惠仁,傅湘琦,向丽华,等.肝郁证的动物实验研究——激怒刺激对大白鼠血液流变学的影响[J].中医杂志,1991,32(6):45-48.
[5]成秀梅,杜惠兰,李丹.寒凝血瘀证动物模型的创建[J].中国中医基础医学杂志,2005,11(8):604-605.
[6]任建勋,林成仁,王敏,等.多因素整合建立气滞血瘀证动物模型研究[J].中药药理与临床,2007,23(5):210-211.
[7]宁天一,王婷婷,程嘉艺.气滞血瘀证大鼠H2S/CSE、CBS体系的变化[J].中药药理与临床,2012,30(5):234-237.
[8]高嘉良,陈光,何庆勇,等.治疗气滞血瘀证中成药组方规律分析[J].中国中药杂志,2017,42(1):187-191.
[9]和岚,蒋文跃,毛腾敏.注射肾上腺素模拟“气滞”复制急、慢性血瘀模型初探[J].中国中西医结合杂志,2004,24(3):244-246.
[10]章正祥,曹克刚,王芬,等.皮下注射肾上腺素复制气滞血瘀模型的血流动力学初探[J].天津中医药,2011,28(1):9-11.
[11]王艳,郑国庆,王明杰,等.治风活血法对微循环气滞血瘀模型的影响[J].现代中西医结合杂志,2005,14(13):1689-1691.
[12]刘丽芳,曾群,金蓉鸾,等.中药水蛭各部位提取物对高分子葡聚糖所致大鼠血瘀模型的影响[J].中成药,2003,25(7):589-590.
[13]陈守强.高黏血症动物模型研究进展[J].中国微循环,2003,7(6):395-396.
[14]任宏义,任周新.“气滞血瘀”证动物模型的建立[J].实验动物科学,1994,11(3):29-31.
[15]唐已婷,陈家旭.三种中药复方对慢性束缚应激大鼠下丘脑—垂体—肾上腺轴的调节[J].北京中医药大学学报,2002,25(3):23-26.
[16]钟小兰,吕志平,钱令嘉,等.束缚所致肝郁证动物模型肝组织蛋白质组的差异表达研究[J].中医杂志,2006,47(5):371-373.
[17]金光亮,南睿,郭霞珍.慢性应激肝郁证大鼠模型的建立[J].北京中医药大学学报,2003,26(2):18-21.
[18]金光亮.论情志与情志病因[J].中华中医药杂志,1997,12(3):9-11.
[19]李峰,杨维益,梁嵘,等.从中医学看肝脏调节应激反应的作用[J].北京中医药大学学报,1998,21(1):20-22.
[20]王阶,陈可冀,翁维良,等.血瘀证诊断标准的研究[J].中国中西医结合杂志,1998,18(10):585-587,589.
[21]赵日霞,郭瑾,唐纯志,等.针刺治疗对躁狂模型大鼠行为学及睡眠潜伏期的影响[J].疑难病杂志,2016,15(4):412-415.
[22]宋程程,王志斌,苏斌,等.常用大鼠血瘀证模型的比较研究[J].北京中医药大学学报,2014,37(2):94-98.
[23]侯万儒.胆盐的生理作用[J].生物学通报,1990,35(11):17,21.
[24]王友兰,胡志宇,张凤翔,等.丙基硫氧嘧啶对正常Sprague-Dawley大鼠脂肪代谢的影响[J].中国医学研究与临床,2003,1(12):9-10.
[25]Velagaleti R S,Massaro J,Vasan R S,et al.Relations of lipid concentrations to heart failure incidence:the Framingham Heart Study[J].Circulation,2009,120(23):2345-2351.
[26]Rubinstein J,Pelosi A,Vedre A,et al.Hypercholesterolemia and myocardial function evaluated via tissue doppler imaging[J].Cardiovasc Ultrasound,2009,7(1):56-62.
[27]Martins F,Campos D H S,Pagan L U,et al.High-fat diet promotes cardiac remodeling in an experimental model of obesity[J].Arq Bras Cardiol,2015,105(5):479-486.
[28]Maczewski M,Maczewska J.Hypercholesterolemia exacerbates ventricular remodeling in the rat model of myocardial infarction[J].J Card Fail,2006,12(5):399-405.
[29]苗兰,潘映红,任建勋,等.气滞血瘀证模型大鼠血清蛋白质组学初步研究[J].中国中医基础医学杂志,2008,14(2):106-107.
[30]苗兰,潘映红,任建勋,等.血府逐瘀汤对气滞血瘀证大鼠血清蛋白质组表达的影响[J].中国实验方剂学杂志,2008,14(4):24-28.
[31]周象贤,周萍.七情学说与应激理论之特征比较[J].医学与哲学,2001,22(6):49-50.
[32]袁肇凯,黄献平,范伏元,等.心病气血辨证面色变化特点及面部血管容积图检测分析[J].中医杂志,2001,42(3):173-175.
[33]袁肇凯,杨运高,黄献平.气滞血瘀证与气虚血瘀证面色及面部血流图观察[J].中国中西医结合杂志,1995,15(12):734.
[34]张永杰,黄西园.冠心病气滞气虚血瘀证血液流变学及心功能比较[J].辽宁中医杂志,1996,23(9):394.
[35]胡志希,袁肇凯,顾星,等.基于光电血流容积中医色诊脉诊的研究与对策[J].中西医结合心脑血管病杂志,2006,4(9):782-785.
[36]吴锐,穆松牛,余淑娇.五种血瘀证亚型实验家兔模型的比较研究[J].河南中医,2010,30(2):146-147.
[37]胡文娟,张秉韬,吴锐.5种血瘀证亚型家兔模型球结膜微循环改变的比较[J].中国中西医结合杂志,2013,33(9):1261-1266.
[38]胡文娟,张秉韬,吴锐.气虚血瘀证与气滞血瘀证家兔模型的球结膜微循环改变比较[J].新中医,2013,45(4):168-171.
[39]牛雯颖,张玉昆,武爽,等.气滞血瘀模型大鼠红细胞膜生物学研究[J].中国当代医药,2013,20(14):6-8.
[40]李丽琦.三种血瘀模型红细胞膜生物学差异性及寒冷刺激血瘀模型方证相关实验研究[D].哈尔滨:黑龙江中医药大学,2012.
[41]梁耀月,李佳佳,董世芬,等.3种不同血瘀证动物模型的建立与评价[J].中国药理学通报,2016,32(10):1468-1473.
[42]王婷婷,贾乘,陈宇,等.大鼠气滞血瘀证模型的建立及影响因素分析[J].中国中药杂志,2012,37(11):1629-1633.
[43]王婷婷,贾乘,宁天一,等.两种气滞血瘀证造模方法的比较[J].中华中医药学刊,2013,31(1):157-158.
[44]宁天一,王婷婷,姜静,等.气滞血瘀证大鼠NO/NOS体系的变化[J].世界中医药,2013,8(1):71-73.
[45]宁天一,王婷婷,程嘉艺.气滞血瘀证大鼠H2S/CSE、CBS体系的变化[J].中药药理与临床,2012,28(5):234-237.
[46]赵艳,于昕,时丽丽,等.消栓通络方有效成分组对大鼠急性血瘀模型的影响[J].药学学报,2012,47(5):604-608.
[47]李伟霞,黄美艳,唐于平,等.大鼠急性血瘀模型造模方法的研究与评价[J].中国药理学通报,2011,27(12):1761-1765.
[48]贾丹兵,于淼,李乃民,等.寒凝气滞血瘀证大鼠动物模型的建立及评价[J].中医药信息,2014,31(4):75-77.
[49]秦书芝.三首活血化瘀方药对气滞血瘀模型大鼠红细胞膜生物学指标的研究[D].哈尔滨:黑龙江中医药大学,2014.
[50]赵慧辉,王伟.病证结合证候模型研究基本思路[J].中华中医药杂志,2006,21(12):762-764.
[51]刘丹彤,马小娜,张小勇,等.子宫内膜异位症气滞血瘀证大鼠模型的建立及评价[J].中医药学报,2012,40(2):31-35.
[52]马小娜,刘丹彤,闫军堂,等.两种子宫内膜异位症大鼠模型的血液流变学及单胺类神经递质比较研究[J].中华中医药学刊,2012,30(1):179-181.
[53]李炜,段金廒,刘培,等.采用雌性SD大鼠探索建立适宜于气滞血瘀证妇科疾病特点的模型评价体系[J].中国中药杂志,2013,38(8):1211-1218.
[54]李敬林,王太一,王禄增,等.2型糖尿病证病结合动物模型的研究[J].中国比较医学杂志,2007,17(8):473-475.
[55]陈嘉斌,柴可夫,郑杨,等.三种方法建立糖尿病气滞血瘀证型大鼠模型的对比实验研究[J].浙江中医药大学学报,2013,37(3):234-239.
[56]蒋继宏.2型糖尿病大鼠血瘀气滞模型实验研究[D].沈阳:辽宁中医药大学,2006.
[57]鲁兴隆.肺抑瘤膏治疗非小细胞肺癌气滞血瘀证临床观察与实验研究[D].济南:山东中医药大学,2015.
[58]彭召云,郑心,鲁兴隆.肺抑瘤膏对气滞血瘀质Lewis肺癌小鼠肿瘤生长及VEGF-C表达的影响[J].时珍国医国药,2015,26(12):2895-2896.
[59]吴飞彪,邹练.前列腺汤对大鼠气滞血瘀型慢性前列腺炎的影响[J].中国性科学,2014,23(3):55-57.
[60]陈可冀,宋军.病证结合的临床研究是中西医结合研究的重要模式[J].继续医学教育,2007,8(19):12-15.
[61]李凤文,须惠仁,张问渠,等.肝郁气滞血瘀的临床和实验研究[J].中医杂志,1991,24(10):47-49.
[62]D'Aquila P S,Peana A T,Carboni V,et al.Exploratory behaviour and grooming after repeated restraint and chronic mild stress:effect of desipramine[J].Eur J Pharmacol,2000,399(1):43-47.
[63]Roy M,David N,Cueva M,et al.A study of the involvement of melanin-concentrating hormone receptor 1(MCHR1)in murine models of depression[J].Biol Psychiatry,2007,61(2):174-180.
[64]赵海滨,刘子旺,张秀静.电针肝俞、期门对肝气郁结模型大鼠行为学的影响[J].广州中医药大学学报,2012,29(1):30-33.
[65]Green A D,Barr A M,Galea L A.Role of estradiol withdrawal in‘anhedonic’sucrose consumption:a model of postpartum depression[J].Physiol Behav,2009,97(2):259-265.
[66]包祖晓,赵国平,何贵平,等.肝肾阳虚型抑郁症大鼠模型的建立与评价[J].中华中医药学刊,2015,33(1):42-45.
[67]Kapusta D R,Jones S Y,Dibona G F.Opioids in the systemic hemodynamic and renal responses to stress in spontaneously hypertensive rats[J].Hypertension,1989,13(6 Pt 2):808-816.
[68]Mccubbin J A,Surwit R S,Williams R B,et al.Altered pituitary hormone response to naloxone in hypertension development.[J].Hypertension,1989,14(6):636-644.
[69]Millan M J,Przewocki R,Jerlicz M,et al.Stressinduced release of brain and pituitary beta-endorphin:major role of endorphins in generation of hyperthermia,not analgesia[J].Brain Res,1981,208(2):325-338.
[70]毛海燕,叶林,叶向荣.肝郁证大鼠中枢神经递质变化的观察[J].福建中医药,2002,33(2):17-18.
[71]唐照亮,宋小鸽,袁静,等.艾灸对寒凝血瘀证大鼠活血化瘀作用的实验研究[J].中国中医基础医学杂志,2000,6(4):43-46.
[72]任路,李浩.关于肝郁证动物模型研究现状及存在问题的思考[J].中医药学报,2006,34(4):44-46.
[73]Bousquet W F,Miya T S,Sanchez C.Modification of stress responses in histamine-depleted rats[J].Br J Pharmacol Chemother,1966,27(1):177-184.
[74]Kvetnansky R,Mikulaj L.Adrenal and urinary catecholamines in rats during adaptation to repeated immobilization stress[J].Endocrinology,1970,87(4):738-743.
[75]马如飞.束缚应激加重挤压伤大鼠肠道损伤及内质网应激蛋白的表达变化[D].石家庄:河北医科大学,2016.
[76]李莉,张晓静,刘威,等.儿茶酚胺在束缚应激大鼠肺损伤中的作用[J].河北医科大学学报,2017,38(5):501-505.
[77]刘楠.束缚应激加重挤压伤大鼠孤束核损伤[D].石家庄:河北医科大学,2015.
[78]闫珊珊,窦维华,董少龙,等.血瘀证动物模型的制作及存在问题的探讨[J].中国中医基础医学杂志,2004,10(2):35-37.
[79]陈彦辛.子宫内膜异位症证候分布研究与病证结合动物模型的研制[D].广州:广州中医药大学,2013.
[80]邢建华,翟红莉.中医证候动物模型研究近况[J].中国疗养医学,2007,16(2):68-69.
[81]马小娜.病证结合子宫内膜异位症大鼠模型的建立与评价[D].北京:北京中医药大学,2011.
[82]吕爱平.病证结合动物模型研究:从理论创新到技术挑战[J].中国中西医结合杂志,2013,33(1):6-7.
[83]韦薇,徐凤芹.气滞血瘀证客观化研究进展[J].中西医结合心脑血管病杂志,2011,9(5):608-609.
[84]钱小奇,张敏.中医证诊断的特点、现状和展望[J].湖南中医药导报,2000,6(12):5-6,29.