《哈尔滨医科大学-毒理学课件-毒物的生物转运与生物转化》由会员分享，可在线阅读，更多相关《哈尔滨医科大学-毒理学课件-毒物的生物转运与生物转化（77页珍藏版）》请在金锄头文库上搜索。
1、2018/10/21,1,BIOTRANSPOTATION AND BIOTRANSFORMATION OF TOXICANTS,毒物的生物转运与生物转化,CHAPTER 3,2018/10/21,2,ABSORPTION,CELL MEMBRANES,INTRODUCTION,DISTRIBUTION,EXCRETION,BIOTRANSFORMATION,BIOTRANSPOTATION,2018/10/21,3,INTRODUCTION,Disposition process（ADME）:Absorption（吸收） Distribution（分布） Metabolism（代谢） Exc
2、retion（排泄）,Page 24,2018/10/21,4,2018/10/21,5,研究外源化学物ADEM过程的意义： 阐明外源化学物毒作用机制，阐明对化学物处置的种属差异，可用于预测人类暴露化学物后的处置及在毒性中的作用。 有助于阐明化学物的联合作用机制。 通过改变外源化学物的ADME过程来预防和治疗化学中毒。,2018/10/21,6,2018/10/21,7,生物膜与生物转运,Biological Membrane and Biotranspotation,2018/10/21,8,Biomembrane（生物膜）,A,Phospholipid bilayer,2018/10/21
3、,9,Biotrospotation Mechanisms (生物转运的机理）,Passive Transport（被动转运）,Simple Diffusion（简单扩散） Filtration（滤过） Facilitated Diffusion（易化扩散）,Page 25,B,2018/10/21,10,Active Transport（主动转运）,Cytosis（膜动转运）,Endocytosis（胞吞） Exocytosis（胞吐）,Phagocytosis（吞噬） Pinocytosis（胞饮）,2018/10/21,11,Passive Transport (被动转运）,1. Sim
4、ple Diffusion ：also be called as lipid diffusion, most toxicants cross cell membranes by simple diffusion.,2018/10/21,12,Factors Related to the Simple Diffusion,The concentration gradient across the membrane.（膜两侧的浓度梯度）,The lipid solubility *lipid /water partition coefficient（脂溶性：脂水分配系数）,The ionizati
5、on form ionization constant, pKa（解离状态：解离系数）,2018/10/21,13,2. Filtration,When water flows in bulk across a porous membrane, any solute small enough to pass through the pores flows with it. Results from the hydrostatic and/or osmotic pressure. 由于水压和渗透压产生的水流可顺压差携带化学物穿过膜孔。,2018/10/21,14,3. Facilitated D
6、iffusion,Facilitated diffusion is similar to active transport but dose not move molecules against a concentration gradient. Furthermore, it is not energy-dependent, and metabolic poisons will not inhibit this process.,2018/10/21,15,Active Transport（主动转运）,Characters*:,Chemicals are moved against conc
7、entration gradients.逆浓度梯度转运,The transport system is saturated at high substrate concentration and exhibits a transport maximum. 转运量有一定极限，当外源化学物达一定浓度时，载体可达饱和状态。,2018/10/21,16,The transport system has the potential for competitive inhibition between compounds that are transport by the same transporter
8、. 由同一载体转运的两种化学物间可出现竞争性抑制。,The system requires expenditure of energy, so that metabolic inhibitors block the transport process. 该系统需消耗能量，因此代谢抑制剂可阻止此转运过程。,The transport system is selective for certain structural feathers of chemical . 载体对转运的外源化学物有特异选择性。,2018/10/21,17,Cytosis（膜动转运）,Cytosis is proposed
9、mechanisms for cell membrane to transport particles. Endocytosis also be called as phagocytosis when the particles are solid;the process is called pinocytosis when the particles are liquid. (吞噬 ：摄入固体； 胞饮:摄入液体；)Exocytosis is a process transport the particles out of the cells.,2018/10/21,18,2018/10/21
10、,19,2018/10/21,20,Absorption 吸 收,Page 26,2018/10/21,21,The process by which toxicants cross body membranes and enter the bloodstream is referred to as absorption.,The main sites of absorption are the gastrointestinal tract, respiratory tract, and skin.,2018/10/21,22,（1）Absorption by the Gastrointest
11、inal Tract,The GI tract is one of the most important sites where toxicants are absorbed. Absorption of toxicants can take place along the entire GI tract.,Absorbed by simple diffusion, filtration, pinocytosis, even active transport.,2018/10/21,23,Because gastric juice is acidic and the intestinal co
12、ntents are nearly neutral, the lipid solubility of weak organic acids or bases can differ markedly in these two areas of the GI tract.,e.g. Benzoic acid, which is a weak acid, exists in the stomach mainly in the nonionized form, and is thus readily absorbed. Aniline, a weak base, existing mainly in
13、the ionized form, is poorly absorbed. In the small intestine, the reverse is true.,Absorbed by passive transport in the GI tract,2018/10/21,24,影响胃肠道吸收的因素：,化学物的结构和理化性质；,胃肠蠕动情况；,胃肠道充盈程度；,肠道中的细菌菌群；,2018/10/21,25,（2）Absorption by the Respiratory Tract,The main site of absorption in the respiratory tract
14、 is the alveoli in the lungs.,Toxicants absorbed by the lungs are usually gases, vapors of volatile or volatilizable liquids,and aerosols.,2018/10/21,26,Factors Related to the absorption in the lungs,The solubility of the gas in the blood .blood/gas partition coefficient * (血/气分配系数),The large alveol
15、ar area, high blood flow, and proximity of the blood to the alveolar air.,The size of particles.,2018/10/21,27,Schematic diagram of the absorption and translocation of chemicals by lungs.,2018/10/21,28,（3）Absorption through the Skin,To be absorbed through the skin, a toxicant must pass through the e
16、pidermis or appendages (sweat and sebaceous glands and hair follicles).,化学毒物经皮吸收主要通过表皮细胞，也可通过皮肤附属器官如毛囊、汗腺和皮脂腺等吸收（仅占0.1%1.0%）。,2018/10/21,29,Diagram of a cross section of human skin.,2018/10/21,30,The Process of Absorption through the Skin,The first phase of percutaneous absorption is diffusion of th
17、e toxicant through the epidermis, which, especially is its stratum corneum, is the most important barrier.,一阶段：穿透阶段（相）,外来化合物透过皮肤表层即角质层的过程 （是限速阶段）,2018/10/21,31,The second phase of percutaneous absorption is diffusion of the toxicant through the dermis, which contains a porous, nonselective, aqueous diffusion medium. Toxicants pass through this area by diffusion and enter the systemic circulation.,
