中医分型“消”胆固醇结晶

怎会有胆固醇结晶正常人胆汁中有三种主要脂类,即胆固醇、卵磷脂和胆汁酸。脂溶性胆固醇在胆汁酸和磷脂的帮助下,能完全溶解在胆汁中,不会有胆固醇结晶析出。但是,如果胆汁中的胆固醇含量超过了胆汁酸和磷脂溶解胆固醇的能力,此时就会析出胆固醇结晶而发生沉淀。析出的胆固醇结晶相互聚结,久而久之便会形成胆固醇结石。     

脂质异常与胆囊胆固醇结石形成关系

目的探讨脂质异常与胆囊胆固醇结石形成的相互关系。方法对50例胆囊胆固醇结石患者（结石组）与30例对照组空腹静脉血血脂进行测定,同时收集新鲜胆囊胆汁化学法测定胆汁中胆固醇（CHD）,胆汁酸（TBA）及磷脂（PL）的含量并计算胆固醇饱和指数（CSI）,评价各指标间的关系。同时应用免疫组化方法检测CD68在50例胆固醇结石患者胆囊壁（结石组）和30例对照组标本中的表达。结果实验组血清中TC、TG、LDL值及胆汁中胆固醇、CSI、PL较对照组高,而HDL和胆汁中胆汁酸低于对照组,P〈0.05差异有统计学意义。结论脂质异常与胆结石的形成关系密切。     

熊去氧胆酸对胆总管结石内镜下逆行胰胆管造影取石术后患者肝功能改善及预防结石复发的疗效观察

<正>胆总管结石是胆道系统的常见疾病,临床表现为上腹绞痛、寒战、高热、黄疸,严重者可合并急性梗阻性化脓性胆管炎、感染中毒性休克,甚至危及生命,常规手术创伤大、结石易残留、术后并发症多,目前内镜下逆行胰胆管造影取石术(endo-scopic retrograde cholangiopancreatography,ERCP)是治疗胆总管结石主要方法之一~([1])。胆总管结石患者中80%为胆固醇结石~([2]),熊去氧胆酸(ursodeoxy-cholic acid,UDCA)是熊胆中主要胆汁酸提取物,是一种亲水性的胆酸,可促进人体胆汁酸的分泌,降低胆汁中胆固醇和胆固醇酯的含量,增加肝脏过氧化氢     

胆红素可抑制胆囊胆汁中碳酸钙的析出

碳酸钙是胆囊结石的一个重要成分，它一旦成为沉淀析出，就能起晶核作用，在其周围逐步沉积形成胆固醇性结石或色素性结石。正常人体胆汁含有一个或多个抑制因子能够阻抑氯化钙和碳酸氢钠过饱和溶液中碳酸钙为沉淀析出。临床研究发现钙性胆石症患者体内胆囊胆汁中抑制因于水平低于健康人。本文报告体外试验中胆红素对胆囊胆汁中碳竣钙沉淀析出的抑制作用。体外试验所用的胆石和胆囊胆汁取自3组共24例接受胆囊切除术的病人，其中无结石的慢性胆囊炎、碳酸钙结石和胆固醇结石患者各8例。试验用25mmol／L碳酸氢钠溶液10ml，在100rPm速度搅拌下…     

成石胆汁组分及成核特性的研究

研究了22例胆囊胆汁的成分及成核特性。其中胆固醇混合性结石组9例，色素性结石组5例，对照组8例。结果显示：胆固醇混合性结石组胆囊胆汁中总胆盐减少，总胆盐中胆固醇溶解能力较强的胆盐的比例下降，胆汁脂类干重下降．卵磷脂相对升高，胆固醇单水结晶形成时间缩短；色素性结石组胆囊胆汁的总胆盐及脂质干重下降；各组胆囊胆汁胆固醇饱和度差异无显著性。     

成石胆汁组分成核特性的研究

研究了２２例胆囊胆汁的成分及成核特性。其中胆固醇混合性结石组９例，色素性结石组５例，对照组８例。结果显示：胆固醇混合性结石组囊胆汁中总胆盐减少，总胆盐中胆固醇溶解能力较强的胆盐的比例下降，胆汁脂类干重下降，卵磷脂相对升高，胆固醇单水结晶形成时间综合蛞；系性结石组胆囊胆汁的胆盐及脂质干重下降；各组胆囊胆汁胆固醇饱和度差异无显性。     

血清结合甘胆酸测定的临床意义

结合甘胆酸(Conjugated GlycocholicAcid,CG)是胆汁酸的主要成份,胆汁酸又是胆汁的主要成份。在肝细胞中的7-α羟化酶的作用下,由胆固醇转化而成。胆汁酸可分为:游离胆汁酸和结合胆汁酸,后者毒性很低,并以钠盐形式存在于胆汁和血液中,餐后胆囊收缩胆汁酸随胆汁排入十二     

高脂旦白血症与胆囊疾病

分泌到胆汁中的胆固醇与卵磷脂及胆汁酸形成可溶性胶粒。由于某些因素影响胆汁酸、磷脂和胆固醇的分泌比例失常,致使胆汁中胆固醇处于过饱和状态。按照现代观点胆汁中胆固醇的过饱和状态是造成人体发生胆固醇性胆石症的原因。     

熊去氧胆酸的临床应用进展

熊去氧胆酸(ursodeoxycholic acid,UDCA)是由胆固醇衍生而来的天然亲水性胆汁酸,可通过抑制胆固醇在肠道内的重吸收和降低胆固醇向胆汁中的分泌,从而降低胆固醇的饱和度,临床上主要用于胆石症、胆汁淤积性肝病、胆汁反流性胃炎、原发性硬化性胆管炎等的治疗。本文从UDCA临床应用和指南推荐角度,总结其在疾病的应用、不良反应和药学监护等,为UDCA的临床合理应用提供参考。     

熊去氧胆酸的临床新用途

熊去氧胆酸(Ursodeoxycholic acid,UDCA)为天然胆汁酸的一种化学制剂,是一种亲水性胆酸。通过抑制肝脏胆固醇的合成,减少胆汁胆固醇的分泌,降低胆汁胆固醇的饱和度,增加胆固醇在胆汁中的溶解度,致使胆石溶解。也可增加胆汁分泌量,松弛胆管口括约肌产生利胆作用。此外还可减少肝脏脂肪,促进肝糖元之蓄积。抑制肝、肌肉中乳酸的生成,也能抑制消化酶和消化液的分泌。故用于治疗胆囊炎、     

Bile acid sequestrants: Mechanisms of action on bile acid and cholesterol metabolism

Summary Interruption of the enterohepatic circulation of bile acids by cholestyramine or colestipol influences the hepatic metabolism of cholesterol in many ways. The synthesis of bile acids is increased, as reflected by a several-fold increase in the activity of the cholesterol 7 hydroxylase, the rate-determining enzyme in bile acid synthesis. The increased metabolism of cholesterol to bile acids causes an enhanced demand of cholesterol in the hepatocytes, which respond with both new synthesis of cholesterol, as reflected in a several-fold increase of the HMG-CoA reductase activity, and increased expression of LDL receptors. As a consequence, the plasma level of LDL-cholesterol is lowered. The hepatic secretion rate of VLDL particles is increased. Cholestyramine therapy does not affect the output of biliary lipids or the cholesterol saturation of bile, indicating that treatment with bile acid sequestrants should not be associated with any increased risk of gallstone formation.     

Bile Acid Transporters: Structure,Function, Regulation and Pathophysiological Implications

Specific transporters expressed in the liver and the intestine, play a critical role in driving the enterohepatic circulation of bile acids. By preserving a circulating pool of bile acids, an important factor influencing bile flow, these transporters are involved in maintaining bile acid and cholesterol homeostasis. Enterohepatic circulation of bile acids is fundamentally composed of two major processes: secretion from the liver and absorption from the intestine. In the hepatocytes, the vectorial transport of bile acids from blood to bile is ensured by Na⁺ taurocholate co-transporting peptide (NTCP) and organic anion transport polypeptides (OATPs). After binding to a cytosolic bile acid binding protein, bile acids are secreted into the canaliculus via ATP-dependent bile salt excretory pump (BSEP) and multi drug resistant proteins (MRPs). Bile acids are then delivered to the intestinal lumen through bile ducts where they emulsify dietary lipids and cholesterol to facilitate their absorption. Intestinal epithelial cells reabsorb the majority of the secreted bile acids through the apical sodium dependent bile acid transporter (ASBT) and sodium independent organic anion transporting peptide (OATPs). Cytosolic ileal bile acid binding protein (IBABP) mediates the transcellular movement of bile acids to the basolateral membrane across which they exit the cells via organic solute transporters (OST). An essential role of bile acid transporters is evident from the pathology associated with their genetic disruption or dysregulation of their function. Malfunctioning of hepatic and intestinal bile acid transporters is implicated in the pathophysiology of cholestatic liver disease and the depletion of circulating pool of bile acids, respectively. Extensive efforts have been recently made to enhance our understanding of the structure, function and regulation of the bile acid transporters and exploring new potential therapeutics to treat bile acid or cholesterol related diseases. This review will highlight current knowledge about structure, function and molecular characterization of bile acid transporters and discuss the implications of their defects in various hepatic and intestinal disorders.     

Biosynthesis of bile acids in mammalian liver.

The biosynthesis of bile acids in mammalian liver and its regulation, together with the physiological role of bile acids, are reviewed in this article. Bile acids are biosynthesized from cholesterol in hepatocytes. Several steps are involved including epimerisation of the 3beta-hydroxyl group, reduction of the delta4 double bond to the 5beta-H structural arrangement, introduction of alpha-hydroxyl groups at C7 or C7 and C12 and, finally, oxidative degradation of the side chain by three carbon atoms. This gives the primary bile acids, cholic and chenodeoxycholic acids. Cholesterol-7alpha-hydroxylation is the rate determining step in the biosynthesis of cholic and chenodeoxycholic acids. Feedback regulation of cholesterol biosynthesis occurs by various mechanisms including termination of the synthesis of specific cytochromes P-450, modulation of specific cytosol proteins, short-term changes in the process of phosphorylation-dephosphorylation and changes in the capacity of the cholesterol pool as a substrate. Prior to being exported from the liver, bile acids are conjugated with glycine and taurine to produce the bile salts. After excretion into the intestinal tract, primary bile acids are partly converted to secondary bile acids, deoxycholic and lithocholic acids, by intestinal microorganisms. The majority of bile acids is absorbed from the intestinal tract and returned to the liver via the portal blood, so that only a small fraction is excreted in the feces. Bile acids returned to the liver can be reconjugated and reexcreted into the bile in the process of enterohepatic recycling. In addition to the physiological function of emulsifying lipids in the intestinal tract, bile acids are particularly important in respect of their ability to dissolve and transport cholesterol in the bile.     

Bile acid sequestrants and the treatment of type 2 diabetes mellitus

Bile acids promote bile formation and facilitate dietary lipid absorption. Animal and human studies showing disturbed bile acid metabolism in diabetes mellitus suggest a link between bile acids and glucose control. Bile acids are activating ligands of the farnesoid X receptor (FXR), a nuclear receptor with an established role in bile acid and lipid metabolism. Evidence suggests a role for FXR also in maintenance of glucose homeostasis. Animal and human studies employing bile acid sequestrants (bile acid binding agents), which interrupt the enterohepatic circulation of bile acids and effectively reduce plasma cholesterol, support a link between bile acid and glucose metabolism. In lipid-lowering trials, bile acid sequestrants, such as colesevelam hydrochloride, colestyramine (cholestyramine) and colestilan (colestimide), have also been shown to lower plasma glucose and glycosylated haemoglobin levels, suggesting the utility of these agents as a potential therapy for type 2 diabetes. In this article, we review the relationship between bile acid metabolism and glucose homeostasis, and present data demonstrating the utility of bile acid sequestrants in the management of diabetes.     

Free fatty acids in gallstones in mice fed a diet containing cholic acid

In mice, combined addition of 1% cholesterol and 0.5% cholic acid to a diet induced cholesterol gallstones within 40 days as a result of the supersaturation of cholesterol in the bile, as has been reported. The major component of the gallstone was cholesterol, which was measured by HPLC. In this study, however, single addition of 1% cholic acid to a diet, which did not decrease cholesterol solubilizing capacity in bile, contributed to gallstone formation in mice within 50 days. The gallstones thus formed contained a large amount of palmitic acid. In the hepatic bile of this animal, palmitic acid was also detected; however, no solid material was observed by light and polarized-light microscopes. Free fatty acids such as palmitic acid seem to be dissolved in a complex micelle composed of bile acids and lecithin. This probably causes gallstone formation by reducing cholesterol solubilizing capacity in bile.     

A practical guide to the nonsurgical treatment of gallstones.

Until recently, cholecystectomy was the only treatment available for symptomatic gallstone disease. During the past 20 years, better understanding of the pathogenesis of cholesterol gallstone disease has led to alternative nonsurgical methods for treating gallstones in selected groups of patients. Use of 2 naturally occurring bile acids, chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), was reported in 1972 and 1975, respectively, for successful dissolution of cholesterol gallstones in humans. Both these bile acids act by reducing cholesterol secretion in bile, thus enabling it to solubilise more cholesterol from the stone surface. Micellar solubilisation is involved, together with liquid crystal formation in the case of UDCA. Having been extensively studied in clinical trials to assess efficacy and safety, both these compounds are now available for general use. The efficacy of CDCA can be enhanced by single bedtime dose administration and by taking a low cholesterol diet. Bedtime administration also enhances the effect of a suboptimal dose of UDCA. CDCA induces dose-related diarrhoea and hypertransaminaemia, and UDCA can induce calcification of gallstones, thus rendering them resistant to medical dissolution. A combination of the 2 bile acids at half the recommended dose for each has become an accepted practice for reducing adverse effects, and this may also enhance efficacy. One of the main problems of bile acid therapy is that dissolution of gallstones is a very slow process. Use of extracorporeal shockwave lithotripsy (ESWL) to break the stones into smaller fragments, with concurrent use of bile acids, has been shown to speed dissolution rate and to achieve complete gallstone dissolution in 78% of selected cases within 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

The gut-to-breast connection - interdependence of sterols and sphingolipids in multidrug resistance and breast cancer therapy

Almost all classes of bioactive lipids such as cholesterol and cholesterol derivatives, phospholipids and lysophospholipids, eicosanoids, and sphingolipids are critically involved in tumorigenesis. However, a systematic analysis of the distinct tumorigenic functions of lipids is rare. As a general principle, lipids either act directly by binding to receptors and other cell signaling proteins in growth control, or indirectly by regulating membrane organization such as the formation of membrane microdomains (lipid rafts) that modulate receptor or other membrane protein function. Lipid rafts are known to be formed by cholesterol and the sphingolipids or ceramide derivatives sphingomyelin and glucosylceramide (cholesterol-sphingomyelin-glucosylceramide or CSG rafts). In this review, we discuss the interconnection of sphingolipids with cholesterol and its derivatives in breast cancer drug resistance. Bile acids are cholesterol derivatives that are first synthesized in the liver (primary bile acids) and then metabolized by intestinal bacteria giving rise to secondary bile acids. They activate farnesoid X receptor (FXR), which inhibits cholesterol conversion to primary bile acids and induces the expression of drug resistance proteins. We introduce a novel model by which bile acid-mediated activation of FXR may promote the formation of CSG lipid rafts that trans-activate drug resistance proteins in breast cancer. Since breast cancer stem cells express high levels of drug resistance proteins, our model predicts that serum bile acids promote breast cancer stem cell survival and metastasis. Our model also predicts that FXR antagonists in combination with sphingolipid biosynthesis inhibitors may be promising candidates for novel drugs in lipid therapy of breast cancer.     

Influence of rifampin on serum markers of cholesterol and bile acid synthesis in men

OBJECTIVE: It has been demonstrated in preliminary studies that rifampin, a semisynthetic antibiotic and known inducer of hepatic cytochrome P450 3A4, reduces serum concentrations of total bile acids only in individuals with liver disease and elevated serum bile acid levels. METHODS: We studied the effect of rifampin on concentrations of surrogate serum markers of cholesterol and bile acid synthesis as well as of cholesterol absorption in 10 male subjects before and after administration of rifampin (600 mg/day) for 6 days. Cholesterol and its precursors were analyzed by gas-liquid chromatography (GLC), bile acid intermediates and individual bile acids by isotope-dilution methods using GLC-mass spectrometry (MS) or by high-performance liquid chromatography (HPLC). RESULTS: Treatment with rifampin resulted in a 70% increase (p = 0.008) of the serum concentration of the bile acid precursor 7alpha-hydroxy-4-cholesten-3-one, which is a marker for bile acid production. Serum total cholesterol was not altered, however, treatment with rifampin elevated the ratio of lathosterol to cholesterol, an indicator of cholesterol synthesis, by 23% (p = 0.037). Interestingly, serum concentration of total bile acids decreased slightly by 29% (p = 0.022), mainly due to a lowering of the secondary bile acid, deoxycholic acid (-60%; p = 0.005). CONCLUSION: A 6-day treatment with rifampin induces a reduction of deoxycholic serum concentrations in healthy men associated with a moderate increase of serum markers of bile acid and endogenous cholesterol synthesis.