黃曲霉毒素B1（AFB1）是已知的黃曲霉毒素中研究最深也是毒性最強(qiáng)的一類霉菌次級代謝產(chǎn)物。肉雞攝入經(jīng)AFB1污染的飼料,通常會引起中毒,降低肉雞的免疫力,并造成嚴(yán)重的經(jīng)濟(jì)損失。經(jīng)證實(shí),肝臟是蓄積和代謝AFB1的主要器官,AFB1經(jīng)肝臟代謝產(chǎn)生的有毒代謝產(chǎn)物殘留在肉雞體內(nèi),可以造成肉雞肝損傷甚至癌癥;殘留在肉雞組織中的AFB1的代謝物通過食物鏈可被人類攝入,從而產(chǎn)生公共衛(wèi)生危害。目前,關(guān)于肉雞體內(nèi)的CYP2A6在AFB1致肉雞亞慢性肝損傷中所扮演的角色尚不明確。姜黃素是從姜黃根莖中提取的多酚類化合物,具有抗炎、抗氧化、抗腫瘤等作用。近期研究表明,姜黃素在脂肪肝綜合征、肝炎、肝硬化和肝癌等肝臟疾病中起著保護(hù)肝臟的作用。姜黃素能否通過影響細(xì)胞色素酶p450表達(dá)尤其是CYP2A6對AFB1誘導(dǎo)AA肉雞亞慢性肝損傷發(fā)揮保護(hù)作用尚不清楚。研究表明,AFB1屬于前致癌物,須通過肉雞肝臟的細(xì)胞色素酶p450的生物活化后才能發(fā)揮其毒性和致癌作用,且代謝酶存在種屬的差異。已有文獻(xiàn)報(bào)道證明,人類肝臟中CYP2A6以及鼠源的CYP2A5是同源物,分別為人或鼠體內(nèi)催化AFB1代謝活化為若干種致癌物質(zhì)（毒物）的C... 

【文章來源】：東北農(nóng)業(yè)大學(xué)黑龍江省 211工程院校

【文章頁數(shù)】：55 頁

【學(xué)位級別】：碩士

【文章目錄】：
Abstract in Chinese
Abstract in English
1 Introduction
    1.1 Aflatoxins
        1.1.1 Description of aflatoxins
        1.1.2 Types of Aflatoxin
        1.1.3 Overview of aflatoxin B1
        1.1.4 Metabolism and bioactivation of AFB1
    1.2 Liver phase-I （cytochrome p450） enzymes
        1.2.1 Introduction to cytochrome p450 enzymes
        1.2.2 Nomenclature of CYP450 enzymes
        1.2.3 Role of CYP450 enzymes in xenobiotics and drug metabolism
        1.2.4 Applications of CYP450
    1.3 Illustration of CYP2A family
        1.3.1 CYP2A subfamily and CYP2A6 enzyme
        1.3.2 CYP2A6 expression and its role in hepatic injury
        1.3.3 Current perspectives of CYP2A6
    1.4 Curcumin
        1.4.1 Introduction to curcumin
        1.4.2 Preventive and therapeutic uses of curcumin
        1.4.3 Effect of curcumin on cytochrome p450 enzymes
        1.4.4 Curcumin as an effective drug against AFB1 toxicity
    1.5 Purpose and significance of the study
2 Material and methods
    2.1 Material
        2.1.1 Drugs and Chemical reagents
        2.1.2 Kits and Apparatus
        2.1.3 Arbor Acres broilers
        2.1.4 Preparation of the main solutions used in experiments
    2.2 Methods
        2.2.1 Animal experiment
        2.2.2 Histopathological examination
        2.2.3 CYP2A6 gene primer designing and polymerase chain reaction
        2.2.4 Extraction and isolation of Ribonucleic acid （RNA） and quantitative real time qPCR
        2.2.5 Determination of CYP2A6 enzyme activity
        2.2.6 Enzyme linked immunosorbant assay （ELISA） for CYP2A6 enzyme
        2.2.7 Statistical analysis
3 Results
    3.1 Effects of AFB1 on liver weight of broilers
    3.2 Effects of AFB1 on body weight of broilers
    3.3 Liver histopathology
    3.4 Polymerase chain reaction （PCR） of CYP2A6 gene, sequencing and construction of phylogenetic tree
    3.5 Effect of curcumin on AFB1-induced CYP2A6 mRNA expression
    3.6 Effect of curcumin on AFB1-induced CYP2A6 enzyme activity
    3.7 Effect of curcumin on AFB1-induced CYP2A6 protein expression level
    3.8 Effect of curcumin on AFB1-induced CYP1A1 mRNA expression
    3.9 Effect of curcumin on AFB1-induced CYP1A2 mRNA expression
    3.10 Effect of curcumin on AFB1-induced CYP3A4 mRNA expression
4 Discussion
    4.1 Effect of AFB1 on body weight and liver weight of Arbor Acres broiler
    4.2 AFB1 induced liver injury
    4.3 Role of CYP2A6 enzyme in bioactivation of AFB1
    4.4 Curcumin successfully inhibited cytochrome p450 enzymes-mediated bioactivation of AFB1 in AA broiler liver
5 Conclusion
Acknowledgement
References
Papers published in the period of Ph.M. education



本文編號：2930771