文献翻译带练09 Enterohepatic recycling
Enterohepatic recycling occurs by biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation and intestinal deconjugation.Cycling is often associated with multiple peaks and a longer apparent half-life in a plasma concentration-time profile. Factors affecting biliary excretion include drug characteristics (chemical structure, polarity and molecular size),biotransformation and possible reabsorption from intrahepatic bile ductules. Intestinal reabsorption to complete the enterohepatic cycle may depend on hydrolysis of a drug conjugate by gut bacteria. Bioavailability is also affected by the extent of intestinal absorption, gut-wall P-glycoprotein efflux and gut-wall metabolism.
肠肝循环是通过胆道排泄和肠内溶质的重吸收来实现的，有时伴有肝结合和肠道去结合。中，肠肝循环循环通常与血药浓度-时间曲线中的多个峰值和较长的表观半衰期有关。影响胆道排泄的因素包括药物特性(化学结构、极性和分子大小)、生物转化和可能有的肝内胆管的重吸收。肠道重吸收完成肠肝循环可能依赖于肠道细菌对药物结合物的水解。生物利用度还受肠道吸收程度、肠壁P-糖蛋白外排和肠壁代谢的影响。
In enterohepatic recycling, foreign chemicals entering the alimentary tract are absorbed into portal venous blood by enterocytes, removed from blood by uptake into hepatocytes, secreted into the bile, and then deposited back into the intestinal lumen where they may be reabsorbed by intestinal cells and available for recycling.enterohepatic recirculation may prolong the pharmacological effect of certain drugs and drug metabolites. Of particular importance is the potential amplifying effect of enterohepatic variability in defining differences in the bioavailability, apparent volume of distribution and clearance of a given compound. Genetic abnormalities, disease states, orally administered adsorbents and certain coadministered drugs all affect enterohepatic recycling.
在肠肝循环中，进入消化道的外来化学物质被肠上皮细胞吸收进入门静脉血液，经肝细胞摄取从血液中排出，分泌到胆汁中，再沉积回肠腔，在肠腔中可被肠细胞重吸收，循环利用。肠肝循环可能延长某些药物和药物代谢产物的药理作用。在确定给定化合物的生物利用度、表观分布体积和清除方面的差异时，肠肝变异性的潜在放大效应是非常重要的。基因异常、疾病状态、口服吸附剂和某些联合用药都影响肠肝循环。
文献翻译带练10 Bile acid nuclear receptor
Nuclear receptors (NRs) are ligand-dependent transcription factors that are involved in various biological processes including metabolism, reproduction, and development. Upon activation by their ligands, NRs bind to their specific DNA elements, exerting their biological functions by regulating their target gene expression. Bile acids are detergent-like molecules that are synthesized in the liver. They not only function as a facilitator for the digestion of lipids and fat-soluble vitamins but also serve as signaling molecules for several nuclear receptors to regulate diverse biological processes including lipid, glucose, and energy metabolism, detoxification and drug metabolism, liver regeneration, and cancer. The nuclear receptors including farnesoid X receptor (FXR), pregnane X receptor (PXR), constitutive androstane receptor (CAR), vitamin D receptor (VDR), and small heterodimer partner (SHP) constitute an integral part of the bile acid signaling.
核受体是配体依赖性的转录因子，参与包括代谢、生殖和发育在内的各种生物学过程。在被其配体激活后，核受体与特定的DNA元件结合，通过调节靶基因表达发挥其生物学功能。胆汁酸是在肝脏中合成的类似洗涤剂的分子。它们不仅是脂类和脂溶性维生素消化的促进剂，还充当多个核受体的信号分子，以调节多种生物学过程，包括脂质、葡萄糖和能量代谢、解毒和药物代谢、肝再生和癌症。核受体包括法尼醇X受体（FXR）、孕烷X受体（PXR）、组成性雄甾烷受体（CAR）、维生素D受体（VDR）和小异二聚体伴侣（SHP）构成胆汁酸信号传导的一个组成部分。
Bile acid synthesis is the most significant pathway for catabolism of cholesterol and for maintenance of whole body cholesterol homeostasis. Bile acids are physiological detergents that absorb, distribute, metabolize, and excrete nutrients, drugs, and xenobiotics. Bile acids also are signal molecules and metabolic integrators that activate nuclear farnesoid X receptor (FXR) and to regulate glucose, lipid, and energy metabolism. The gut-to-liver axis plays a critical role in the transformation of primary bile acids to secondary bile acids, in the regulation of bile acid synthesis to maintain composition within the bile acid pool, and in the regulation of metabolic homeostasis to prevent hyperglycemia, dyslipidemia, obesity, and diabetes.
胆汁酸合成是胆固醇分解代谢和维持全身胆固醇稳态的最重要途径。胆汁酸是吸收、分配、代谢和排泄营养物质、药物和外源性物质的生理洗涤剂。胆汁酸也是信号分子和代谢整合因子，可激活核法尼醇X受体（FXR），并调节葡萄糖、脂质和能量代谢。肠肝轴在初级胆汁酸转化为次级胆汁酸、调节胆汁酸合成以维持胆汁酸池中的成分、调节代谢稳态以预防高血糖、血脂异常、肥胖和糖尿病方面起着关键作用。