儿科
词汇介绍
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解析
enterohepatic
释 义 adj. 肠肝的
例 句 Hypercholic acidemia is caused by the interruption of enterohepatic circulation and deterioration of hepatic function after portasystemic shunt. 高胆酸血症主要为门体分流术后肝肠循环阻断和肝功能恶化所致。
circulation 英/sɜːkjʊ'leɪʃ(ə)n/ 美/,sɝkjə'leʃən/
释 义 n. 流通，传播；循环；发行量；（图书的）借出
例 句 Hemoglobin was the carrier of oxygen in blood circulation. 血红蛋白是血液循环中输送氧的载体。
概述
概述
胆汁酸的肠肝循环是一个非常严格的调控过程，机体利用胆汁流和胆汁池大小，通过一系列的网状调控机制使胆汁酸的合成、摄取、排泄以及重吸收过程处于动态平衡，以维持机体稳态。而在病理状态下，这种调控机制出现障碍，胆汁流量减少，循环系统及细胞内胆汁蓄积造成细胞损伤。
胆汁酸的肝肠循环
在肠道中，结合型胆汁酸在回肠末端和结肠上段肠道细菌的作用下解离成游离型胆汁酸，随之被细菌7a-脱氢酶转化为次级胆汁酸：脱氧胆酸和石胆酸， 二者在结肠通过弥散作用重吸收或通过粪便排出体外。因此，在回肠末端结合型胆汁酸和游离型胆汁酸混合存在。结合型胆汁酸在小肠前端几乎不能被吸收，但占绝大多数的T/G-BA在回肠中能够被顶膜的顶端钠依赖型胆汁酸转运体主动有效地重吸收入肠上皮细胞，并与回肠胆汁酸结合蛋白结合转运至基底膜，在基底膜终末腔面的异源二聚体有机溶质转运蛋白参与下，重吸收入门静脉随血流运回肝 脏，经肝细胞窦状隙膜的Na+/牛磺胆酸共转运多肽主动吸收进入肝细胞，重吸收的胆汁酸在肝细胞中再与新合成的结合型胆汁酸一起由肝细胞毛细胆管膜的胆盐输出泵分泌进入胆道系统。另外，游离型胆汁酸在小肠和结肠通过被动弥散的形式重吸收入肠上皮细胞，再由肝细胞窦状，隙膜的有机阴离子转运多肽摄入肝细胞，最后在肝细胞内进行加工并分泌到毛细胆管。胆汁随进食流入肠腔，完成一次胆汁酸的肠肝循环。那些没有被肝细胞重新摄人的胆汁酸会扩散到全身循环，最终可能会通过肾和尿液排泄。
相关疾病
胆汁淤积是一种遗传性或获得性的病理状态，指肝细胞或胆管水平上的胆汁生成、分泌和（或）流动发生障碍，正常通过胆汁流人十二指肠而排出体外的一些物质，如胆汁酸、胆红素等滞留体内，从而导致一系列临床表现。各种原因导致以胆汁淤积为主要表现的肝胆疾病常统称为胆汁淤积性肝病。遗传性的胆汁淤积症包括进行性家族性肝内胆汁淤积症（PFIC）、良性再发性肝内胆汁淤积症、先天性胆汁酸合成障碍、Alagille综合征、Citrin蛋白缺陷引起的新生儿胆汁淤积症、ARC综合征等；获得性胆汁淤积常见于感染、药物、激素、妊娠、肿瘤、胆道闭塞等因素引起。随着胆汁淤积分子机制研究的深入，逐步认识到胆汁酸的肠肝循环在许多胆汁淤积性肝病中发挥重要作用，通过减少肠肝循环，可减少肝脏和循环系统内胆汁酸等的储积并减少胆汁酸池，可能是治疗多种胆汁淤积性肝病的有效手段。
复制标题口服 β-葡萄糖醛酸苷酶联合给药增加经肠肝再循环的广泛葡萄糖醛酸化药物的暴露
发表时间：2012-02-21
影响指数：3.1
作者： Gary Eichenbaum
期刊：J Pharm Sci
Strategies for increasing the bioavailability of compounds that undergo extensive first-pass metabolism have generally fallen into two categories: chemical and drug delivery based. Chemical-based approaches include structural modification of the parent compound, coadministration of an enzyme inhibitor, inhibition of efflux transporters such as p-glycoprotein, or coadministration of a buffering agent such as sodium bicarbonate. Structural modification is a common approach used prior to candidate selection and in the development of backup compounds. For example, nitrofenac, a structural analog of diclofenac, does not produce the intestinal toxicities (e.g., ulcerations) that are observed with diclofenac.An example of coadministration of an inhibitor is methoxaslen, which is a CYP2A6 inhibitor that blocks the metabolism of nicotine and has been shown to decrease nicotine clearance, increase nicotine bioavail- ability, and decrease smoking behaviors.Inhibitors such as ketoconazole have been used to reduce the extent of metabolism of cytotoxic and antiviral drugs, thereby improving the bioavailability and efficacy of these agents.Drug delivery approaches include bypassing duodenal or gastric metabolism and delivering a compound to the colon through the use of a controlled-release delivery system or bypassing the first pass to liver through transdermal, oral cavity, or parenteral routes.Although both chemical- and drug delivery-based approaches can be effective for overcoming extensive first-pass metabolism, they can also have limitations. For example, structural modification of acompound that is in clinical trials generates a com- pletely new chemical entity that requires a new development program, including nonclinical toxicology, resulting in increased time, cost, and risk. Furthermore, chemical modification may not be feasible in cases wherein the site of metabolism is essential for the biological activity of the chemical series. In cases wherein multiple enzymes form a toxic metabolite, the use of enzyme inhibitors may be of limited value. If there are no regional differences in gut metabolism or there is poor colonic absorption, it is unlikely that an oral controlled-release delivery approach would deliver adequate drug levels.
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