【作者】 王明翠；

【导师】 李凡；

【作者基本信息】 吉林大学 ， 病原生物学， 2009， 硕士

【摘要】 病原菌侵染宿主并增殖,诱发急性和慢性炎症。炎症和多种重大疾病如癌症、动脉粥样硬化、衰老、关节炎等疾病密切相关。因此对抗菌消炎药物的研究及开发意义重大。许多传统中草药具有抗菌消炎的功能。近年来,随着现代生物医学的发展,越来越多的中草药抗菌消炎成分被揭示出来,这些成分的抑菌及抗炎机理也逐渐被阐明。然而,抑制细菌生长和抑制炎症是两个不同的过程。中药中的有效成分是否可以对细菌的生长进行抑制?这些成分是否具有直接的抗炎作用?这些问题的阐明的研究中药抗菌消炎的机理至关重要。本文首先研究了中药单体没食子酸内酯、3,4,5-三甲氧基苯甲酸、黄芩苷、葛根素、杨梅黄酮、莽草酸、焦性没食子酸对几种常见病原菌的抑菌作用,测定了这些化合物对细菌的最低抑制浓度。发现从中药中分离得到的化合物没食子酸内酯、杨梅黄酮、焦性没食子酸具有较好的抑制细菌生长作用。在此基础上,选取了中药单体杨梅黄酮进行了细胞和动物抗炎实验。杨梅黄酮是一种天然黄酮类化合物,具有抗氧化、抗炎、抗菌、抗癌活性。然而,它的抗炎机理和其对致炎细胞因子的释放的影响目前尚无研究。我们检测了杨梅黄酮对在炎症中起关键作用的一些基质金属蛋白酶的抑制活性,鉴定了它对氧化性细胞损伤的保护作用,并用动物模型监测了它对治疗炎症和对促炎症反应细胞活素类物质释放的效应。我们发现杨梅黄酮在体外对MMP-1,-2,-9,-14和-16显示强烈的抑制作用,杨梅黄酮的预处理能够有效地缓解H2O2引起的细胞损伤。在体内,杨梅黄酮能减少细菌脂多糖(LPS)引起的TNF-α和IL-12释放,抑制角叉胶引起的鼠急性炎症。总之,结果表明,杨梅黄酮有效地降低了细胞的氧化损伤、降低了炎症因子TNF-α和IL-6的分泌、显著抑制了小鼠的炎症反应。本论文首次发现了几种对常见病原菌具有抗性的中药单体,揭示了中药单体杨梅黄酮的抗炎效果和分子机制。结果表明某些中药单体如杨梅黄酮可以同时抑制病原菌的生长并且抑制炎症的进程,为中药抗菌消炎的机制的阐明做出了一定贡献。更多还原

【Abstract】 Pathogens infect the host and the proliferation induces acute and chronic inflammation. Inflammation closely linked to the occurrence and development a variety of major diseases. Many traditional Chinese herbal medicines are with anti-bacterial anti-inflammatory functions. Moreover, a growing number of herbal anti-bacterial anti-inflammatory constituents and their antimicrobial and anti-inflammatory mechanism been elucidated. However, the inhibition of bacterial growth and inhibit inflammation are two different processes. What are active ingredients in the Chinese herbal medicines? Can they suppress the growth of bacteria? Whether these components have a direct anti-inflammatory effect? The study of these issues to clarify the mechanism of anti-inflammatory anti-bacterial medicine is essential. This paper attempts to explore these issues and problems.This paper studied the traditional Chinese medicine monomer gallic acid lactone, 3,4,5 - trimethoxy benzoic acid, baicalin, puerarin, myricetin, shikimic acid, pyrogallic acid of several common pathogens antibacterial action of these compounds were determined by the minimum inhibitory concentration of bacteria. Found that isolated from traditional Chinese medicine compound gallic acid lactone, myricetin, pyrogallic acid with a good role in inhibiting bacterial growth. On this basis, the selected TCM monomers myricetin were inflammatory cells and animal experiments.Myricetin (3, 3’, 4’, 5, 5’, 7-hexahydroxyflavone), a natural flavonoid commonly found in is a tea, wines, fruits and many plants, has been shown to exhibit antioxidation, anti-inflammatory, antimicrobial and anticarcinogenic activities. However, the anti-inflammatory mechanism of myricetin and the effects of myricetin on proinflammatory cytokines release are not well defined. Here we examine the inhibitory activity of myricetin on a number of matrix metalloproteinases, evaluate its protective effect on oxidative cell damage, and used animal model to monitor the its effect to treat inflammation and on proinflammatory cytokines releases. We found myricetin showed strong inhibition to matrix metalloproteinase-1, -2, -9, -14 and -16 enzymatic activities in vitro. Pretreatment of myricetin effectively relieved H2O2 induced cell damage. In vivo, myricetin reduced the release of TNF- and IL-12 induced by LPS. Moreover, mice with acute inflammation induced by carrageen was suppressed though myricetin treatment. Overall, our data suggest that myricetin can attunate inflammation at least though its MMP inhibition and antioxidative activities.In this paper we first found several of common pathogens are subjected to the inhibition of traditional Chinese medicine compounds, revealing the anti-inflammatory medicine monomer myricetin effect and molecular mechanism. The results show that some traditional Chinese medicine compounds, such as myricetin can simultaneously inhibit the growth of pathogenic bacteria and to inhibit the inflammation process. Our study has made a certain contribution to the clarification anti-bacterial anti-inflammatory mechanism of Chinese medicines.更多还原