虎斑游蛇抗炎作用及其作用机制的实验研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
虎斑游蛇Natrix tigrina Lateralis(Berthold),又名野鸡脖子,它是一种有着重要药用价值的动物类药材,为游蛇属无毒蛇。虎斑游蛇具有祛风湿,止痹痛,解毒等功能,因为其治疗风湿性关节炎、骨结核等疾病疗效显著,因此在民间被广泛应用。但对其抗炎作用及作用机理方面的系统研究尚未见报道。本实验通过建立多种实验性炎症的动物模型,观察虎斑游蛇的乙醇提取物对急性、慢性炎症的作用,并对其抗炎作用机理进行探讨,从而为临床开发用药和进一步研究提供科学的实验依据。现对本实验的研究方法和结果简述如下:
     1.抗炎实验研究
     通过虎斑游蛇对蛋清致大鼠足跖肿胀、二甲苯致小鼠耳肿胀、醋酸致小鼠腹腔毛细血管通透性增高和大鼠棉球肉芽肿影响的实验研究,揭示虎斑游蛇的乙醇提取物对蛋清致大鼠足肿胀、二甲苯致小鼠耳肿胀、醋酸致小鼠腹腔毛细血管通透性增高及大鼠棉球肉芽肿均有抑制作用,与空白对照组比较,均有显著性差异,且呈剂量依赖性。
     2.抗炎机理研究
     通过虎斑游蛇对去肾上腺大鼠蛋清性足跖肿胀、对大鼠胸腺重量和对小鼠肝糖原含量及对小鼠嗜酸性粒细胞数量影响的实验研究,表明虎斑游蛇能够抑制去肾上腺大鼠蛋清性足跖肿胀,使小鼠胸腺的重量减轻,增加小鼠肝糖原的含量而减少嗜酸性粒细胞的数量,提示虎斑游蛇具有肾上腺皮质激素样作用。又通过对大鼠肾上腺内维生素C含量及血浆皮质醇含量测定的实验研究,结果发现虎斑游蛇醇提物并不降低肾上腺内维生素C含量,只显现出降低肾上腺内维生素C含量的趋势,反而降低大鼠血浆皮质
    
    黑龙江中医药大学硕士学位论文
    中文摘要
    醇含量,显示出虎斑游蛇对大鼠肾土腺皮质激素的合成和释放无
    作用,其抗炎作用与下丘脑一垂体一肾上腺皮质轴的关系不大,其
    抗炎作用与皮质轴关系需有待于进一步深入研究。
    3.对炎症介质的作用
     通过虎斑游蛇对大鼠炎性渗出物‘},组胺和5一挂色胺含量的测
     声
    定,发现其能够减少渗出液中组胺和5一烃色胺的含量,表明虎斑
    游蛇能够抑制炎症介质组胺和5一经色胺的释放,而发挥抗炎作用。
     综上所述,通过对虎斑游蛇抗炎作用及其机理的实验研究,
    揭示了其具有肾上腺皮质激素样作用的特点,同时能够抑制炎症
    介质的释放,而发挥抗炎作用,但与下丘脑一垂体一肾上腺皮质系
    统的作用无关。
     通过上述实验研究,基本全面评价和解释了虎斑游蛇在抗炎
    方面的作用特点及作用机理,亦初步验证了虎斑游蛇祛风湿,止
    痹痛,治疗风湿病的传统功用,为合理开发和药川虎斑游蛇资源
    提供了坚实的科学依据。
Natrix tigrina Lateralis (NTL) is also named neck-pheasant. It is one of the zonic medicinal materials with important medicinal value, and it is nontoxic snake belonging to Colubridae. NTL has the function of expelling wind, eliminating dampness, relieving pain due to rheumatism, detoxification, etc., and because of its remarkable curative effect to rheumatoid arthritis and bone tuberculosis, and so forth, it has been applied far and wide in Chinese traditional folk. But there is no report on the systematic study of anti-inflammation action and mechanism of anti-inflammation. In our experiment, we observe the curative effect of NTL ethanol extract to acute and chronic inflammation in rats and mice by using several experimental study models, and its mechanism of anti-inflammation is discussed. The purpose is to provide a scientific experimental basis for clinical development and further research. Method and results are as follows:
    1.The experimental study of inflammation
    This experiment opens out that NTL ethanol extract can inhibit the edema of rat hind paw induced by fresh egg white, the ear-swelling of mice induced by xylene, the celiac capillary of mice induced by acetic acid and the proliferation of grannuloma of rat induced by cotton ball through experimental study of effect of NTL on edema of rat hind paw induced by fresh egg white, ear-swelling of mice induced by xylene, celiac capillary of mice induced by acetic acid and proliferation of grannuloma of rat induced by cotton ball, and there is significant difference between NTL and control group, in a dose-dependent manner.
    
    
    2.The study of mechanism of its anti-inflammation
    This experiment shows that NTL can inhibit the edema of hind paw induced by fresh egg white in adrenalectomized rat, reduce the weight of thymus in rat, increase the content of hepatic glycogen ,but decrease eosinophil of mice through experimental
    study of effect of NTL on edema of hind paw induced by fresh egg
    white in adrenalectomized rat, weight of thymus in rat, content of
    hepatic glycogen and eosinophil of mice. The results indicate that NTL has the analogous function to cortin. In the experimental study on the content of Vitamin C in adrenal gland and plasma hydrocortisone, the result shows NTL can't decrease the content of Vitamin C in adrenal gland, just appear the trend of decreasing the content of Vitamin C in adrenal gland, on the contrary, it can decrease the content of plasma cortisol in rat, which shows it has no effect to the synthesis and liberation of rat's adrenal cortical hormone.and its anti-inflammation function hasn't much relationship to hypothalamus-pituitary-adrenal axis, so the relationship between the anti-inflammation and cortex needs further research.
    3. The effect to inflammatory mediators
    In the assay of inflammatory exudates and 5-HT content, it can decrease the content of histamine and 5-HT in exudates, which shows that NTL effects anti-inflammation through inhibiting the liberation of inflammatory mediators histamine and 5-HT.
    To sum up, the experimental study on the anti-inflammation function and its mechanism of NTL shows it has the analogous function to the adrenal cortical hormone, and can effect anti-inflammation function though inhibiting the liberation of inflammatory mediators, but this function has no relationship to
    
    hypothalamus-pituitary-adrenal axis.
    Through the experimental study above, the anti-inflammation characteristic and mechanism of NTL is given basically overall evaluation and explanation, and its traditional function of expelling wind, eliminating dampness, relieving pain due to rheumatism and
    treating rheumatism is tested elementarily, which provides stable
    scientific basis for reasonable exploiture and use of NTL.
引文
1.冯新.病理生理学.第三版.北京,人民卫生出版社,1990:122
    2.魏文汉.病理上理学.第一版.上海,上海科学技术出版社,1984:388
    3.B.L.缪尔著,苏宝田主泽.病理生理学 疾病机理导轮.北京,人民卫生出社,1987:93
    4.冯新.病理生理学.第三版.北京,人民卫生出版社,1990:123-143
    5.黄新,张阳.激活素:炎症介质家族的新成员.国外医学生理、病理科学与临床分册,2000,20(5):337-339
    6.吴其夏,余应年,卢建.新编病理生理学,人民卫生出版社.第一版,1999:252
    7.徐叔云,丁长海,魏伟.影响炎症免疫反应的药物研究及其思路.药学进展,1997,21(2):76-82
    8.徐叔云,丁长海.抗炎症免疫药物的临床研究进展.药学进展 1997,013(004):238-246
    9.赵尔宓.我国古代对于蛇类的认识.动物学杂志,1980,(4):48-51
    10.李时珍.《本草纲目》(校点本下册),人民卫生出版社,1985:2403
    11.李时珍.《本草纲目》(校点本卜册),人民卫生出版社,1985:2404-2046
    12.赵尔宓.《中药》,上海科学技术出版社,1981。
    13.林乾良,金贻郎.蛇类的临床应用动物学杂志,1979(4)
    14.林乾良,金贻郎.蛇类的临床应用,浙江中医学院通讯,1977(2):43-45
    15.顾剑萍.乌梢蛇的药理研究初报,浙江药学,1986;3(4):4
    16.许正昌,张志敏.蛇毒制剂抗肿瘤体外实验研究,实用癌症杂志,1996.11(4)-239-240
    17. Rabinowich H.Steiner Z.Klajman A.et al.Clonal analysis of human tumor infiltrating lymphocytes reactive with autologous tumor cell:Different target cell specificities of NK-like and cytotoxic T-cell clone.Cell Immunol,1987:-104
    18.仲晓燕.中华眼镜蛇细胞毒素14的纯化及抗癌活性,中国药理学通报,1993,(14):279
    19. Fletcher JE,Jiang MS.possible mechanisme of action of cobra sanke venom cardiotoxins and bee venommelitlin Toxicon
    20.郑虎占,董泽宏,余静.中药现代研究与应用.第六卷.北京学范出版社.1999:
    
    -5892
    21.《中国药用动物志》协作组·中国药用动物志(第一册),1979,204
    22.俞慎初.虫类药临床应用,福建科技出版社,1981,163
    23.李淑莲,赵文静,刘承德.虎斑游蛇药理作用研究Ⅱ,中医药信息,2001,18(1):47
    24.赵文静,李淑莲,徐国旭.虎斑游蛇药理作用研究Ⅰ,中医药信息,2000.17(6):53
    25.马冬平,李宪筑,赵文静.虎斑游蛇对小鼠免疫功能的影响,中医药学报,2003,31 (1):50
    26.吴炳辅.中草药中微量元素研究的现状与展望[J],中草药,1986,(4):38
    27.赵文静,李淑莲,万羽.虎斑游蛇的微量元素含量测定及与乌梢蛇的比较分析,中医药信息,2002,19(4):64
    28.许益民.三十八种蛇类药材的原动物鉴别研究,中药通报,1986:(6):17
    29.国家药典委员会。中华人民共和国药典(一部)。化学工业出版社,2000,59,176,304
    30.王义权,周开亚.蛇类药材的氨基酸分析。基层中药杂志。1996:(3):26
    31.陈奇.中药药理研究方法学.第一版.北京.人民卫生出版社,1993:308
    32.范玉玲,崔福德,杨明世.齐墩果酸和齐酞酸钠对二甲苯引起的小鼠耳肿胀抑制作用研究,中医药研究,2002,018(006):37-381
    33.陈奇.中药药理研究方法学.第一版.北京.人民卫生出版社,1993:305
    34.陈奇.中药药理研究方法学.第一版.北京.人民卫生出版社,1993:366
    35.李仪奎.中药药理实验方法学.第一版.上海.上海科技出版社,1991:232
    36.陈奇.中药药理研究方法学.第一版.北京.人民卫生出版社,1993:779
    37.石晓兰,梁尚华.霜叶红对哮喘大鼠气道阻力、肺顺应性及血嗜酸性粒细胞作用的研究,湖北中医杂志,2000,022(009):50
    38.陈奇.中药药理学.北京.中国中医药出版社,1992:154
    39.陈奇.中药药理学.北京.中国中医药出版社,1992:808
    40.张均田.现代药理实验方法[M].北京.北京医科大学中国协和医科大学联合出版社,1998:1006
    41.李仪奎.中药药理研究方法学.第一版.上海,上海科学技术出版社,1991:233
    42.马洪喜,李冬梅.黄芪皂甙对糖尿病大鼠血清激素水平的影响.微量元素与健康研究,2003,20(4):5
    
    
    43.宋智琦,林熙然.某些炎症介拮抗剂抗过敏作用的实验研究,中华核医学杂志,1982,2(1),4
    44. Rbrook,Direct Solid-phase 1251 RIA of Serum cortisol, Clin Chem. 1978,9:24, 1595
    45.向俭军,陈华粹.组胺的荧光测定法的研究,中国医学科学院学报,1981,3(3):183-186
    46.方福德,周吕,丁濂.现代医学技巧全书,北京医科大学中国协和医科大学联合出版社,第二版,1995:158-162
    47.邹冲之.激素与胸腺退化。国外医学·内分泌分册,1984,4(1):22
    48.张罗修.免疫药理学,第一版,上海医科大学出版社,1992:157-159
    49. Oldenburg NB,Evans-Storms RB,Cidlowski JA.In vivo resistance toglucocortic oid-induced apopotosis in rat thymocytes with normal steroid receptor function in vitro Endocrinology 1997;138(2):810-818
    50.姚泰.生理学,第五版,北京·人民卫生出版社,2002:396
    51. Adachi T.Montojima S.Hirata A.et al.Eosinophil apoptosis caused by theophylline, glucocostieoids,and macroides after stimulation with IL-5.J Allergy Clin Immunol,1996,98(6 pt2):S207
    52. Matsumoto K,Schleimer R P, Saito H.et al,Induction of apoptosis in human eosinophils by anti Fas antibody treatment in vitro,Blood,1995,86(2):1437
    53. Davidsson A,Andersson T, Hellquist HB,Apoptosis and phagocytosis of tissue-dwelling eosinophils in sinonasal Polyps.Laryngoscope,2000,110:111-116
    54.王文魁,沈映君.辛夷抗炎作用的实验研究,成都中医药大学学报,2000,23(1):58-61
    55.杨刚.内分泌生理与病理生理学,第二版,天津科学技术出版社,1996:60-64
    56.殷凯生.组胺研究进展近况,国外医学·生理病理学科分册,1983,3(4):180-183