三黄乙肝胶囊抗乙型肝炎病毒的血清药理学研究

【作者】 徐海波；

【导师】 吴清和；

【作者基本信息】 广州中医药大学 ， 中药学， 2000， 硕士

【摘要】 乙型病毒性肝炎是一种以肝脏炎症和肝细胞变性、坏死为主要病变的常见传染性疾病，其发病率高、起病隐匿、病程迁延，易转化为肝硬化和原发性肝细胞癌。乙型肝炎病毒是乙型肝炎最直接的致病因素，它是一种致病力强、变异性高、抵抗力强的嗜肝DNA病毒，现已严重地威胁着人类的生命健康。 三黄乙肝胶囊由黄芩、大黄、柴胡、黄芪、五味子、甘草组成，具有清热除湿、疏肝健脾的功效。经用于临床多年发现对湿热交阻、肝郁脾虚型急、慢性乙型肝炎具有较好疗效。为了深入探讨其作用机理，我们进行了三黄乙肝胶囊抗乙型肝炎病毒的血清药理学研究。 本课题研究结果表明： （1）三黄乙肝胶囊对HBsAg具有较强的抑制作用。含三黄乙肝胶囊的免血清对HBsAg的抑制作用随着剂量的增加、反应时间的延长而增强，随着HBsAg浓度的升高而减弱。高剂量含三黄乙肝胶囊血清对HBsAg的抑制作用强于含无环鸟苷血清，并与有效氯浓度为250PPM的速消净相当。而三黄乙肝胶囊粗制剂直接体外抑制HBsAg效应更强，甚至优于含药血清。 （2）三黄乙肝胶囊对HBeAg具有较强的抑制作用。含三黄乙肝胶囊的兔血清对HBeAg的抑制作用随着剂量的增加、反应时间的延长而增强，随着HBeAg浓度的升高而减弱。高剂量含三黄乙肝胶囊血清对HBeAg的抑制作用强于含无环鸟苷血清，并与有效氯浓度为250PPM的速消净相当。而三黄乙肝胶囊粗制剂直接体外抑制HBeAg效应更强，甚至优于含药血清。提示三黄乙肝胶囊中的有效成分可能未从胃肠道完全消化吸收或在体内代谢失活。 （3）含三黄乙肝胶囊的兔血清对乙肝病毒DNA聚合酶（HBV DNAP）具有较强的抑制作用，并随着剂量的增加而增强，且高剂量含三黄乙肝胶囊血清对HBV DNAP的抑制作用与含无环鸟苷血清无显著性差异。 （4）高剂量含三黄乙肝胶囊的兔血清对乙肝病毒DNA具有较强的抑制作用，且作用强度与含无环鸟苷血清和有效氯浓度为250PPM的速消净相当。 中文摘回 中药血沽药理学是近10余年来才兴起的一种中药药理体外实验方法。它是将中药或中药复方给动物记田B一定时间后采集动物血液，分离血清，用此含有药物成分的血清进行体外实验的一种实验珊。由于它排除了传统中药体外实验中中药粗制剂本身的理化性质对姻的础，又能反应药抛体内的生帆化过程及其作用结果，因此它实现了体外实验和体内实验的完美结合，在中药药理实验方法的6d＃上具有重大意义。 但作为一种新兴的实验方法，中药血清药理学的理论体系和具体的实验操作均不成熟和完善。本课题从方法学上对目前中药血清药理学中存在的国内外争议颇多的一系列问题进行了探索，同时指明了中药血清药理学在中药现代化研究中应用的广阔前景。更多还原

【Abstract】 Viral hepatitis B is a common infectious disease with the main features of the inflanimatoin of the liver, and the degeneration and necrosis of the hepatocyte. The disease has high mobidity with secret invasion and long course of disease, and it inclines to convert to hepatocirrhosis and primary hepatoma. Hepatitis B virus (HBV) is the most direct pathogenic factor of the viral hepatitis B. I-LBV is a kind of hepadna virus with strong pathogenicity, high mutation and powerful resistance, and it has been greatly threatening the human health and lives nowadays. San Huang ~?Gan Capsule (Sl-IYGC) consists of Huang Qin~ Da Huang~ Chai Hu~ Huang Qi~ Wu Wei Zi.. Gan Cao with the efficiency of clearing away heat-evil and wetness-evil, dispersing the stagnated liver-energy and invigorating the spleen. After having been used clinically for many years, it was found to have significant therapeutic effectiveness on the acute and chronic viral hepatitis B in the type of the retention of dampness-heat in the interior, the stagnation of the liver-qi and the deficiency of the spleen. In order to explore the mechanism of the effectiveness deeply, we canied the study of SHYGC against I-IBV with the seropharrnacological method. The results of the experiment indicate that: (1) SHYGC has significant inhibitory effects on HBsAg. The inhibitory effects on HBsAg of the rabbit sera containing SHYGC become stronger with the dosage improved and the action time prolonged, and they decrease with the l-IBsAg concentration improved. The inhibitory effect on HBsAg of the serum containing hing- dose SHYGC is stronger than that of the serum containing ACV, and is equal to that of Su Xiao Jing containing 2SOPPM available chloiic. The direct external inhibitoiy effects of SHYCIC in original pharmaceutics are more powerful, even stronger than the sera containing SHYGC. (2) SHYGC has significant inhibitory effects on HBeAg. The inhibitory effects on HBeAg of the rabbit sera containing SHYGC become stronger with the dosage 3 improved and die action time prolonged, and they decrease with the HBeAg concentration iniprovecL The inhibitory effect on HBeAg of the senmi containing hing- dose SHYGC is stronger than that of the senmi containing AC~ and is equal to that of Su Xiao Jing containing 25OPPM available chloric. 711ie direct external inhibitory effects of SHYGC in original pharmaceutics are more po~iful, even stronger than the scm containing SHYGC. It probably indicates that the active ingr~1ients of S1-IYGC can not be digested and absorbed completely from gastmintestine, or are inactived by metabolism in vivo. (3) The rabbit scm containing SIIYGC have significant inhibitory effects on HBV DNA polymerases (l-LBV DNAP), and they become stronger with the dosage bnprovecL There is no distinct difference bet~en the inhibitory effect on I-LBV DNAP of the sen.nn containing hing-dose SHYGC and that of the sen~m containing ACV (4) The rabbit sen.tm containing hing-dose SHYGC has significant inhibitory effects on HBV DNA, wi抰ich is equal to that of the serum containing ACV and Su Xiao Jing containing 25OPPM available chloric. Chinese herbal serophaimacology has been a new external testing method of Chinese herbal pharmacology in recent ten yeazs. The method is to sample the blood of the animal ~&4iich have been orally administered Chinese herbs or Chinese heital compl更多还原