胆汁分泌及其对胆管结石形成的影响

介绍胆管胆汁分泌的调节机制，某些激素对胆汁分泌作用的最新进展。胆汁分泌异常极易导致许多肝脏疾病的发生和发展。重点介绍胆汁淤滞对形成肝内胆管结石的影响。     

家兔实验性胆管瘘的制备方法

为观察家兔肝胆汁分泌的生理过程及其调节因素,制备本实验动物模型。制备过程如下。 在麻醉条件下进行无菌手术。腹部常规备皮后,于正中线近剑突处开腹壁。小心分离并结扎肝胆管,以阻止肝胆汁流向胆囊。     

吗啡耐受对家兔肝胆汁分泌的影响

用雄性家兔进行实验。预先在麻醉条件下行灭菌手术,结扎肝胆管,安装胆总管套管和十二指肠套管。实验时可将流出的胆汁经十二指肠套管送回小肠腔。实验后将两套管的体外端用硅胶管连通,使胆汁自然流回十二指肠。 本实验观察了家兔在吗啡耐受前后肝胆汁分泌的情况。结果表明,静脉灌注吗啡(1毫克/公斤,10分钟注完),可使家兔肝胆汁分泌量明显减少。一般在开始灌注后10分钟胆汁流量即开始减少,此后继续减少,     

胆汁分泌的分子调节机制

胆汁形成是多步骤主动转运的过程,经肝细胞基底膜、肝细胞内、肝细胞胆管膜侧的主动转运,位于肝细胞两膜侧的转运蛋白基因多已克隆,其功能改变是胆汁分泌,淤胆性肝病的病理、生理的分子基础.了解其调节机制,为淤胆性肝病的临床治疗提供重要信息.     

赶黄草水提取物利胆退黄作用的研究

目的探讨赶黄草水提取物的利胆退黄作用。方法采用胆管引流法，观察赶黄草水提取物对正常大鼠胆汁分泌量的影响：采用胆管结扎致大鼠梗阻性黄疸模型和α-萘异硫氰酸酯（ANIT）致胆汁淤积模型，观察赶黄草水提取物对模型大鼠血清总胆红素（TBIL）含量、碱性磷酸酶（ALP）活性、γ-谷氨酰转移酶（GGT）活性、门冬氨酸转氨酶（AST）活性、丙氨酸转氨酶（ALT）活性的影响。结果赶黄草水提取物能增加正常大鼠胆汁的分泌量，但对血清TBIL含量无影响；对于胆管结扎所致梗阻性黄疸模型大鼠和ANIT所致的胆汁淤积模型大鼠．赶黄草水提取物能显著降低血清TBIL含量，抑制血清ALP、GGT、AST和ALT活性。结论赶黄草水提取物具有明显的利胆退黄作用。     

消炎利胆胶丸对胆道及肠道平滑肌的作用

消炎利胆胶丸是我院中医学教研室研制的一种复方中药制剂,临床应用证实对胆囊炎、胆石症有较好的疗效。我们将其药用成分用沸水浸泡后制成不同浓度的溶液,观察了其对胆汁分泌及平滑肌的作用。 1.胆汁分泌:将200～250g大鼠随机分成4组,分別灌胃给予消炎利胆胶丸2.49g     

先天性肝门区胆管闭锁的应用解剖学观察

作者观察了9例肝门区胆管闭锁的死婴,对肝外胆道进行了应用解剖学研究。在肝门区胆管闭锁处的纤维团块内,多数可见到数个微细开放的小胆管,并与肝内胆道连通。这种结构基础,为开展肝门、肠吻合术提供了解剖学依据。本文尚介绍了7例临床手术体会。     

大鼠离体肝再灌注模型（IPRL）的建立及其在肝移植器官保存液实验中的意义

目的　为肝脏保存液的研究提供离体肝脏再灌注模型。方法　用大鼠肝移植供体手术方法获取供肝,离体再循环2小时,同健康活体大鼠进行对比,观察胆汁分泌量、胆汁中胆酸及胆红素水平。结果　健康活体大鼠肝和保存时间为0小时的离体再灌注肝的2小时胆汁分泌量分别为206.0±74.8μl     

胆石症的并发症:米瑞之综合征、胆囊、胆总管瘘和胆石性肠梗阻

胆结石作为一种常见病 ,在美国和西欧有 10 %的患病率。但是 2 0 % -3 0 %的患者 ,它仅仅表现为一个症状 ,其中最常见的症状是“胆绞痛”。有症状的胆石症的并发症很少 ,年发生率小于 1%。胆石症最常见的并发症有急性胆囊炎、急性胰腺炎、逆行性胆管炎和胆囊坏疽。较少见的并发症包括米瑞之综合征、胆囊、胆总管瘘和胆石性肠梗阻。米瑞之综合征和胆囊、胆总管瘘是同一疾病发展过程中的两个不同表现 ,在发病初期胆结石嵌顿在胆囊颈部 ,使胆汁分泌受阻 ,引起黄疸。胆结石还可以侵蚀胆管 ,引起胆囊、胆总管瘘。胆石性肠梗阻是指单个或多个胆结…     

肝外胆管梗阻病变MSCT曲面重建胆管成像与MRCP的比较研究

目的比较多层螺旋CT（MSCT）曲面重建（CPR）胆管成像与磁共振胰胆管成像（MRCP）对肝外胆管梗阻病变的诊断价值。方法66例经B超检查提示有肝外胆管梗阻病变的患者，采用单次激发快速自旋回波（SSFSE）序列，行MRCP检查，同期采用10mm层厚层距，使用血管对比剂，行MSCT增强扫描，将门静脉期图像采用2．5mm层厚、1．25mm层距重建，获得轴面源像（ASI），数据传输至图像工作站，作CPR胆管成像。比较CPR胆管成像、MRCP对肝外胆管梗阻病变的定位、定性诊断价值。结果CPR胆管成像、MRCP成功率为100％；CPR胆管成像、MRCP均对肝外胆管梗阻部位做出明确诊断，定位诊断率为100％；CPR胆管成像、MRCP定性诊断率分别为95．5％和80．9％。结论CPR胆管成像、MRCP对肝外胆管梗阻病变均能明确定位，CPR胆管成像定性诊断率明显高于MRCP，CPR胆管成像显示胆管及其周围病变与扩张胆管的关系更直观。     

Tannic acid inhibits cholangiocyte proliferation after bile duct ligation via a cyclic adenosine 5',3'-monophosphate-dependent pathway

Chronic cholestatic diseases are characterized by morphological changes involving cholangiocyte proliferation and functional alterations of secretory capacity. The plant polyphenol tannic acid inhibits the growth of malignant human cholangiocytes. However, the mechanisms by which tannic acid limits excessive cholangiocyte proliferation are unknown. In this study we assessed the effect of tannic acid on cholangiocyte proliferation after bile duct ligation in rats. Tannic acid feeding decreased cholangiocyte proliferation and ductal mass in vivo after bile duct ligation. These changes were associated with functional changes in bile secretion and with decreases of intracellular cyclic adenosine 5',3'-monophosphate. The anti-proliferative effect of tannic acid was associated with a reduction of ERK1,2 phosphorylation. Additionally, tannic acid feeding decreased protein kinase A phosphorylation and activity. Similar changes were observed in isolated cholangiocytes during in vitro incubation with tannic acid. Furthermore, forskolin abolished the anti-proliferative effect of tannic acid on cholangiocyte proliferation after bile duct ligation. In conclusion, the anti-proliferative effects of tannic acid in cholangiocytes involve modulation of ERK1,2 by a cyclic adenosine 5',3'-monophosphate-protein kinase A-dependent pathway. These data suggest that tannic acid may be useful in limiting excessive cholangiocyte proliferation and modulating secretion during cholestasis.     

Effects of digitoxin and lithium, used as a marker of passive Na transport, on secretin-dependent bile flow in the pig

The present study was performed in anaesthetized pigs, and the first aim was to assess the role of Na,K-ATPase in secretin-dependent biliary HCO3 secretion (JbHCO3). Intra-arterial administration of the cardiac glycoside digitoxin (0.2 mg/kg-1) reduced hepatic Na K-ATPase activity, JbHCO3 and secretin-dependent bile flow by 24, 55 and 34% respectively. In the second part of this study lithium (Li) was used as a marker of passive Na transport to assess the electrochemical gradient for Na flux into bile duct lumen during secretin-stimulated bile flow and impeded biliary osmotic water flow by i.v. infusion of glucose. At plasma glucose 85 (73-96) mmol l-1, bile [Na] and [Li] exceeded their concentrations in plasma by 57 and 47% respectively. By using the Nernst equation, transepithelial potential difference (PD) during hyperglycaemia was estimated to be -6.2 (0 to -10.8) mV (ductal lumen negative), which corresponds to a [Li]bile/[Li]plasma ratio of 1.3 (1.0-1.5). The ratio was not significantly different from the observed [Li]bile/[Li]plasma ratio of 1.4 (1.3-1.5). It is concluded (1) that Na, K-ATPase is necessary for JbHCO3, probably by sustaining the cell membrane PD (cell interior negative) which is a driving force for apical electrogenic HCO3 secretion, and (2) transepithelial Li (and hence Na) flux is driven solely by the negative transcellular PD during secretin-stimulated bile flow in the pig.     

Tannic Acid Inhibits Cholangiocyte Proliferation after Bile Duct Ligation via a Cyclic Adenosine 5′,3′-Monophosphate-Dependent Pathway

Chronic cholestatic diseases are characterized by morphological changes involving cholangiocyte proliferation and functional alterations of secretory capacity. The plant polyphenol tannic acid inhibits the growth of malignant human cholangiocytes. However, the mechanisms by which tannic acid limits excessive cholangiocyte proliferation are unknown. In this study we assessed the effect of tannic acid on cholangiocyte proliferation after bile duct ligation in rats. Tannic acid feeding decreased cholangiocyte proliferation and ductal mass in vivo after bile duct ligation. These changes were associated with functional changes in bile secretion and with decreases of intracellular cyclic adenosine 5′,3′-monophosphate. The anti-proliferative effect of tannic acid was associated with a reduction of ERK1,2 phosphorylation. Additionally, tannic acid feeding decreased protein kinase A phosphorylation and activity. Similar changes were observed in isolated cholangiocytes during in vitro incubation with tannic acid. Furthermore, forskolin abolished the anti-proliferative effect of tannic acid on cholangiocyte proliferation after bile duct ligation. In conclusion, the anti-proliferative effects of tannic acid in cholangiocytes involve modulation of ERK1,2 by a cyclic adenosine 5′,3′-monophosphate-protein kinase A-dependent pathway. These data suggest that tannic acid may be useful in limiting excessive cholangiocyte proliferation and modulating secretion during cholestasis.     

Distortion in TGFβ1 peptide immunolocalization in biliary atresia: Comparison with the normal pattern in the developing human intrahepatic bile duct system

Biliary atresia is an important cause of neonatal obstructive jaundice in which there is inflammation, sclerosis and eventual obliteration of the bile duct system. Its onset may be antenatal, affecting the normal development of the biliary system. The intrahepatic biliary system is derived from the ductal plate, a sheath of cuboidal epithelium that appears at the hepatocyte-mesenchymal junction around the portal vein branches at 6 weeks gestation. This epithelial structure is moulded into a network of tubular bile ducts by the proliferating mesenchyme. Certain portions of the ductal plate are selected to become definitive bile ducts, while redundant biliary epithelium is deleted. The molecular dynamics controlling the intra-uterine development of the biliary system in humans are not yet clearly understood. Transforming growth factor-β1 is a cytokine that stimulates mes-enchymal proliferation and inhibits epithelial growth, and has been shown to be important in organogenesis. In the present study, the pattern of TGFβ1 peptide immunolocalization was investigated with the aid of computerized image analysis, in normal human bile duct development and in biliary atresia. TGFβ1 peptide was detected within hepata-cytes and ductal plate epithelium from 7 weeks gestation; increased TGFβ1 immunoreactivity was present within the epithelium of developing bile ducts at 13 weeks gestation, and apical polarization of the cytokine was observed from 16 weeks gestation. In biliary atresia, the TGFβ1 immunoreactivity pattern within the bile duct structures at the porta hepatis and within intrahepatic portal tracts resembled that of the primitive ductal plate, and there was no significant apical polarization. This may indicate a developmental arrest in the normal ductal plate remodelling process in biliary atresia, and suggests an underlying epithelial-mesenchymal interactive disorder.     

Abnormalities of intrahepatic bile ducts in extrahepatic biliary atresia

The infantile cholangiopathies are a group of conditions associated with neonatal jaundice, which include extrahepatic biliary atresia, paucity of intra-hepatic bile ducts and disorders associated with persistence of fetal biliary structures, the so-called ductal plate malformations. Although previously regarded as distinct entities, it has recently been suggested that they may represent parts of a disease spectrum in which the principal process is one of bile duct destruction, the morphological manifestations in individual cases being influenced by the stage of intra-uterine development at which such injury occurs and by the site within the biliary system at which there is maximum damage. To further examine this concept, we have studied liver biopsy specimens from 37 neonates with extrahepatic biliary atresia, with particular reference to abnormalities of the intrahepatic bile ducts. Paucity of intrahepatic ducts, defined as a bile duct: portal tract ratio of less than 0.9, was identified in six cases (16.2%). In eight cases (21.6%) we found concentric tubular ductal structures similar to those observed in ductal plate malformations. In one case, both abnormalities could be demonstrated. Our findings support the concept that there is overlap between the various types of infantile cholangiopathy.     

Morphometric and immunohistochemical characterization of human liver regeneration.

Regeneration in human liver is characterized in part by the formation of ductular structures, so-called ductular hepatocytes in massive hepatic necrosis and bile ductules in mechanical biliary obstruction. In an attempt to characterize the liver regenerative process, we performed image analysis and immunohistochemical staining of the ductular structures in these well defined human liver disorders, 13 cases of massive hepatic necrosis and 9 cases of mechanical biliary obstruction. The proliferation index was determined and the expression of several antigens was localized by immunohistochemical staining using antibodies to alpha-fetoprotein, alpha-1-antitrypsin, albumin, and cytokeratin 19. The ductular structures in adult human liver were compared with the developing ductal plates in 11 fetal livers, ranging in age from 9 to 36 weeks of gestation. Image analysis demonstrated that the mean total area, mean nuclear area, and mean cell size of ductular hepatocytes were significantly larger than those of bile ductules (p < 0.05). The proliferation index of ductular hepatocytes and bile ductules was significantly higher than that of hepatocytes of normal livers (p < 0.02). Bile ducts, bile ductules in mechanical biliary obstruction, ductular hepatocytes in massive hepatic necrosis, and the ductal plate cells in fetal liver showed strong staining for cytokeratin 19, which characterizes intermediate filaments associated with bile duct epithelial cells. Albumin, a liver-specific protein, and alpha-1-antitrypsin, a protease inhibitor, were strongly expressed in ductal plate cells of fetal liver, hepatocytes, and ductular hepatocytes, whereas bile duct cells and bile ductules were negative for albumin. In summary, ductular hepatocytes demonstrate morphometric and immunophenotypic features of both hepatocytes and biliary epithelial cells, whereas bile ductules share characteristics primarily with fetal ductal plates and mature bile ducts. These findings suggest that ductular hepatocytes in massive hepatic necrosis may serve as bipotential progenitor cells, and bile ductules in mechanical biliary obstruction are related to ductal plates of fetal liver.     

Effect of changes in circulating amylase levels on amylase output in bile

The relation between plasma and biliary amylase activity and their relationship to the functional state of the pancreas were studied in anesthetized rabbits. Repetitive intravenous injections of cholecystokinin resulted in a 25-fold rise in the secretion of amylase via the pancreatic duct, followed at first by a 50% increase in plasma amylase concentration and later by a 270% increase in biliary amylase concentration. There was then a gradual, roughly synchronous decline in both plasma and biliary values toward basal level despite a continued highly augmented rate of pancreatic ductal secretion. "Near-total" pancreatectomy completely abolished the effect. These observations are consistent with a cholecystokinin-induced basolateral secretion of amylase from pancreas into blood and its subsequent movement from blood into bile down a concentration gradient. The output of amylase in bile, however, was quite small and does not suggest that biliary transport of amylase has an important function either as a means of secreting and recycling digestive enzyme into the gut or as a major excretory pathway for circulating amylase in the rabbit.     

Ultrastructure of acinar cell injuries in experimental acute pancreatitis created by common bile duct ligation

Morphogenesis of acute pancreatitis induced by ligation of the common bile duct and the ultrastructure of autolytic transformations of acinar cells were studied. Autolytic changes in acinar cells started from the basal zones and then involved the apical zones. Violation of the zymogen granules integrity, interactions of their contents with the adjacent ultrastructures, destruction (melting) of ultrastructures, and formation of huge autophagosomes play an important role in the development of autolysis. Disordered secretion of zymogen granules (foci of their accumulation in the apical zone), hyperplasia and hypertrophy of centroacinar cells and ductal epitheliocytes aimed at restoration of the pancreatic secretion discharge pathways were seen in the retained acini.     

Influence of sodium deoxycholate on morphology, net fluid transport and motility in the small intestine of the rat

Intestinal fluid secretion and motility were induced by luminal perfusion of rat small intestine with sodium deoxycholate, a dihydroxy bile salt for 1-3 h. Changes in intestinal morphology were studied simultaneously with the changes in fluid transport and motility. The results suggest that the bile salt causes epithelial lesions which may lead to a reduced fluid absorption in the villi, thereby explaining part of the total change in net fluid transport caused by the bile salt. Pyrilamine and indomethacin did not influence the bile salt-induced secretion. Based on earlier studies, it is proposed that the major part of the bile salt-evoked secretion is mediated via activation of intramural nervous reflex(es), which also stimulate the intestinal smooth muscle cells.