单纯性肥胖者血清胆汁酸谱研究

目的探讨单纯性肥胖者血清胆汁酸谱的特征,为阐明胆汁酸引发的能量代谢相关机制和探寻新的肥胖生物治疗靶点提供研究依据。方法利用超高效液相色谱-串联质谱(UPLC-MS/MS)联用方法检测体检人群中10名表观正常对照者、10例超重者和10例单纯性肥胖者血清胆汁酸谱的特征。结果表观正常对照组、超重组和单纯性肥胖组血清中14种胆汁酸亚组分均有表达,其中的石胆酸(LCA)、牛磺胆酸(TCA)、牛磺石胆酸(TLCA)和牛磺熊脱氧胆酸(TUDCA)的表达水平最低;14种胆汁酸亚组分在各组间的差异均无统计学意义(P>0.05);单纯性肥胖组的胆汁酸谱中以甘氨鹅脱氧胆酸(GCDCA)和牛磺鹅脱氧胆酸(TCDCA)增高为主;超重组及单纯性肥胖组血清游离型胆汁酸(FBA)和结合胆汁酸(CBA)水平稍低于表观正常对照组,但差异无统计学意义(P>0.05)。结论单纯性肥胖者血清胆汁酸谱中以GCDCA和TCDCA增高为主,但各种胆汁酸亚组分的表达水平与表观正常者相同。     

糖尿病患者胆汁中的胆汁酸

作者研究了17例(男12、女5,年龄24-50岁)重型糖尿病患者胆汁中胆汁酸组成的质与量改变。对照组由8名健康人组成。测定了肝胆汁和胆囊胆汁中下列胆酸的含量(毫克%):牛磺胆酸(TX),牛磺鹅脱氧胆酸((?))+牛磺脱氧胆酸((?)),甘氨胆酸((?)),甘氨鹅脱氧胆酸((?)),甘氨脱氧胆酸((?)),胆酸((?)),脱氧胆酸((?))+鹅脱氧胆酸((?))。测定结果:糖尿病患者胆囊胆汁中(?)的绝对含量和百分比量均升高,分别升高至2.9倍及2倍。在游离胆汁酸中发现(?),其含量百分比平均为6.1%。正常人胆汁中(?)仅为痕迹量。与此改变平行发生的是初级(?)含量与含牛磺酸的胆汁酸     

胆汁酸谱在肺炎和肺癌鉴别诊断中的应用价值

目的 探讨肺癌患者血清胆汁酸谱的变化及其在肺炎与肺癌鉴别诊断中的价值.方法 采用液相色谱-串联质谱法(LC-MS/MS)检测80例肺炎患者(肺炎组)、108例肺癌患者(肺癌组)和106名体检健康者(正常对照组)血清胆汁酸谱[5种游离胆汁酸,包括胆酸(CA)、鹅脱氧胆酸(CDCA)、脱氧胆酸(DCA)、石胆酸(LCA)、...     

血清胆汁酸测定在肝病诊断上的价值:各种胆汁酸分析对肝胆疾病的诊断意义

为了研究各种胆汁酸分析对肝胆疾病的诊断意义,作者用高效液相层析和酶测定法,对8例正常人和76例肝胆疾病患者,进行了血清总胆汁酸(TBA)和各种胆汁酸的测定。正常人和各种病例组的血清胆汁酸分析的特征如下。正常人(8例)的血清中各种胆汁酸浓度(μmol/l)是,①游离型:熊脱氧胆酸(UDCA)0.07±0.04,胆酸(CA)0.14±0.05,鹅脱氧胆酸(CDCA)0.42±0.16,脱氧胆酸(DCA)0.30±0.05,石胆酸(LCA)检不出;②结合型中的(a)甘氨酸结合型(G):甘氨胆酸(GCA)0.16±0.07,甘氨鹅脱氧胆酸(GCDCA)0.47±0.05,甘氨脱氧胆酸(GDCA)0.46±0.26,甘氨石胆酸(GLCA)检不出;(b)牛磺酸结合型(T):牛磺胆酸(TCA)0.16     

ICP患者血清疏水性胆汁酸与miR-18a水平的相关性研究

目的探讨妊娠期肝内胆汁淤积症(ICP)患者血清miR-18a水平与血清疏水性胆汁酸的相关性。方法选取健康对照组、轻度ICP组、中度ICP组、重度ICP组孕妇各40例,分别采用实时定量RT-PCR法检测血清miR-18a水平,高效液相色谱串联质谱法检测疏水性胆汁酸脱氧胆酸、鹅脱氧胆酸、石胆酸、甘氨鹅脱氧胆酸水平;并与血清miR-18a水平进行相关性分析。结果相较于健康对照组,轻度、中度和重度ICP组患者血清miR-18a水平均明显降低,差异有统计学意义(P0.05);相较于轻度ICP组,中度和重度ICP组患者血清miR-18a水平明显降低,差异有统计学意义(P0.05);相较于中度ICP组,重度ICP组患者血清miR-18a水平明显降低,差异有统计学意义(P0.05)。对照组孕妇血清miR-18a水平与疏水性胆汁酸水平无相关性(P0.05);轻度、中度和重度ICP组患者血清miR-18a水平与疏水性胆汁酸水平呈负相关(r=-0.847～-0.531,P0.05)。结论 ICP患者血清miR-18a明显降低,随病情加重,miR-18a水平越低,miR-18a水平与血清疏水性胆汁酸水平呈负相关,可能在ICP的发生、发展中发挥重要作用。     

肝移植术后患者血清胆汁酸代谢的检测及临床意义

目的:评价肝移植术后患者血清总胆汁酸水平、胆酸/鹅脱氧胆酸比值在肝移植术后发生排斥反应及肝功能延迟恢复时的变化规律。方法:选择2004-01/2004-12在大连医科大学器官移植中心进行肝移植手术的患者28例,同时收集大连医科大学附属二院门诊健康体检者和肝硬化患者血清学标本各12例作为对照,所有观察对象均知情同意。采用高效液相色谱检测肝移植术后患者血清中不同种类胆汁酸及总胆汁酸水平,也与常规肝功能监测指标谷草转氨酶和总胆红素加以比较,对肝移植术后患者血清指标与肝功能恢复之间的关系进行综合评价。结果:所有观察对象均进入结果分析,无脱落。①肝硬化组、肝移植组术前患者的血清总胆汁酸水平显著高于正常对照组(P<0.05)。②肝移植患者术后发生排斥反应或肝功能延迟恢复时,血清总胆汁酸水平较术前明显升高(P<0.05),胆酸/鹅脱氧胆酸比值明显降低(P<0.05),且比谷草转氨酶、总胆红素的变化提前发生,随着供肝功能的恢复它们将逐渐恢复正常。结论:总胆汁酸及胆酸/鹅脱氧胆酸比率可以作为肝移植术后发生排斥反应及肝功能延迟恢复的早期诊断指标,其对于肝移植术后急性排斥反应的早期诊断、早期治疗有重大意义。     

胆汁酸代谢及其临床应用

近年来国内已陆续开展血清结合胆酸的测定,经与常规肝功能试验比较,显示其一定的优越性,值得推广应用。 本文拟有关胆汁酸的代谢及其临床应用作一简介,以供参考。 胆汁酸的生成 正常人胆汁的胆汁酸可分为二大类:一、游离胆汁酸,占少量,主要有胆酸(CA),鹅脱氧胆酸(CDCA)、脱氧胆酸(DCA)及小量熊脱氧胆酸(UDCA)和石胆酸(LCA)。二、结合胆汁酸,由游离胆汁酸分别和甘氨酸或牛磺酸结合而成,占绝大部分。     

肝移植术后患者血清胆汁酸的变化及临床意义

目的：探讨肝移植术后患者血清血清胆汁酸水平的变化及其临床应用价值。方法选择本院收治的肝移植术后患者78例,以及同期于本院体检健康者30例。检测并比较受试者血清胆汁酸、门冬氨酸氨基转移酶等肝功能指标的水平。结果 Child-Pugh分级为 A、B、C级的肝移植患者血清胆汁酸水平分别为（1．41±0．28）、（1．91±0．19）、（2．04±0．08）mol／L ,均高于健康者[（0．79±0．09）mol／L ,P＜0．05]。Child-Pugh分级为B级和C级患者,血清胆汁酸水平均高于A级患者（P＜0．05）。在术后第5、7天,出现排异反应的患者血清胆汁酸水平高于未出现排异反应的患者。出现排异反应的患者血清胆酸／鹅脱氧胆酸比值低于术前水平,且术后第5、7天水平均低于未出现排异反应的患者（P＜0．05）。结论血清胆汁酸、胆酸／鹅脱氧胆酸比值能够敏感地反映肝细胞损伤程度,是早期诊断肝移植术后排异反应的良好指标,能够为临床诊断和治疗提供重要参考。     

胆汁酸测定在肝脏疾病中的应用

胆汁酸是存在于胆汁中的一类胆烷酸的总称，在肝细胞内以胆固醇为原料合成初级胆汁酸(胆母鸡及鹅脱氧胆酸)。在肠道内以初级胆酸为原料，在肠道菌酶的作用下形成次级胆酸(脱氧胆酸、石胆酸、熊脱氧胆酸等)。胆汁酸由肝细胞内的微粒体、线粒体、溶酶体合成，主要以结合的形式分泌到胆汁中，在胆汁中含量可达69％。胆汁进入肠腔后，在回肠和结肠，绝大部分胆汁酸被肝细胞所摄取，又因肠肝循环基本上属于闭锁式的．故外周血循环中胆汁酸的浓度较低。当肝胆有疾病时，循环血液中的胆汁酸含量即有不同程度的增加，故血清中总胆汁酸(TBA)可作为肝实质性损伤的灵敏诊断指标。综述如下。     

胆汁酸负荷试验时血清胆汁酸成分的分析

胆汁酸负荷试验对肝脏疾患的诊断有用,但对血中升高的胆汁酸成分的详细情况则不明确。作者在进行熊脱氧胆酸负荷试验后接着又进行了食物负荷试验,将奥山氏的高压液相色谱法与固相酶柱结合来进行血清胆汁酸分析,研究了15种成分在不同时间内的变化,本文报道了其中变化颇大的游离型熊脱氧胆酸(UDC)、甘氨酸熊脱氧胆酸(GUDC)和甘氨酸鹅脱氧腿酸(GCDC)三种。受试者为健康人(N组)4名、急性肝炎恢复期患者(AH组)5例、慢性肝炎(CH组)5例及肝硬化(LC组)5例。清晨空腹,口服UDC 300 mg后,分别在30、60、120、180分钟抽血,然后进食作为早餐服用试验所需的食物(牛奶200ml、蛋黄-     

Fasting and postprandial serum bile acid concentration with special reference to variations in the conjugate profile

Serum bile acids were group-separated by ion exchange chromatography on diethylaminohydroxypropyl Sephadex LH-20 into unconjugated bile acids and bile acids conjugated with either glycine, taurine, glucuronic acid or sulphuric acid. The conjugate moiety was hydrolysed by treatment with a combination of Helix pomatia and cholylglycine hydrolase and the released bile acids analysed by gas liquid chromatography/mass spectrometry. Analysis of fasting and postprandial serum from six healthy subjects showed that, in addition to the primary bile acids, cholic (C) and chenodeoxycholic acid (CDC), secondary bile acids were present to varying extents. Unconjugated serum bile acids were found in four of the six subjects. Glycine and taurine conjugates of C and CDC and their glucuronides and sulphates were found in all subjects. The postprandial increase of serum bile acids was mainly due to increase of the glycine conjugates of C and CDC. After the meal, the ratio C:CDC in glycine and taurine conjugates shifted to lower values.     

Differential diagnostic value in hepatobiliary disease of serum conjugated bile acid concentrations and some routine liver tests assessed by discriminant analysis

Serum concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid were measured with a HPLC-enzymatic assay in 104 patients with hepatobiliary diseases. The capability of discriminating between four major diagnostic categories by the serum bile acid concentrations, alone and in conjunction with five commonly used biochemical liver tests, was evaluated by stepwise linear discriminant analysis. The serum bile acid pattern alone was inferior to the routine liver tests in separating the diagnostic groups. When the two sets of analytes were combined, the generalized group distance (Rao's V) was significantly increased, showing that the serum bile acid pattern contained discriminatory information in addition to the routine liver tests. The gain in correct reclassification of patients obtained by adding the serum bile acids, however, was only marginal.     

Active and Passive Bile Acid Absorption in Man. PERFUSION STUDIES OF THE ILEUM AND JEJUNUM

Absorption of the major human bile acids was studied in 12 healthy volunteers by steady state perfusion of the ileum in 112 experiments and of the jejunum in 48 experiments. Use of a randomized order of four perfusions on 1 day of study and use of up to 4 consecutive days of study in a subject allowed important comparisons of data from the same individuals. That there is active ileal absorption of chenodeoxycholic, glycochenodeoxycholic, and taurocholic acids in man was supported by the finding of saturation kinetics and of competition for absorption among conjugated bile acids. Values for apparent kinetic constants (apparent maximal transport velocity [(*)V(max)] and apparent Michaelis constant) in man are similar to those in other species. The ileum absorbed chenodeoxycholic acid more rapidly than its glycine conjugate, due mainly to a ninefold greater permeability for the free acid. Taurocholate had the highest (*)V(max) and was absorbed more rapidly than glycochenodeoxycholate. Passive permeability of the jejunum to bile acids was twice that of the ileum, and the permeabilities to free and glycine-conjugated chenodeoxycholate were in the same ratio as in the ileum (9: 1). Jejunal permeability to chenodeoxycholic acid was three times that to cholic acid. Variation of intraluminal pH by up to 1.4 units did not influence jejunal uptake of free bile acids. These results, which are comparable with those from animal experiments, provide a basis for estimation of intestinal reabsorption of bile acids in intact man.     

Bile-acid metabolism and the liver.

Primary bile acids are exclusively synthesize, and all bile acids are conjugated, in the liver. When hepatic function is altered by disease, not surprisingly the bile-acid metabolism reflects this change. 1. In chronic liver disorders the glycine: taurine ratio of serum and bile is reduced. 2. In cases of relapsing acute hepatitis and relapsing chronic active hepatitis the serum bile acids are increased, providing an aid to early diagnosis. Their pattern often distinguishes chronic cholestatic conditions from Laennec's cirrhosis. 3. In chronic liver disease, the concentration of intraduodenal bile acids is reduced; when the reduction is severe, this probably accounts for co-existent steatorrhoea. 4. In Laennec's cirrhosis, both the synthesis and pool size of cholic acid are markedly depressed; in primary biliary cirrhosis, however, preliminary data indicate a decrease in the chenodeoxycholic acid component.     

Determination of cholic acid and chenodeoxycholic acid pool sizes and fractional turnover rates by means of stable isotope dilution technique, making use of deuterated cholic acid and chenodeoxycholic acid

A procedure is described for the simultaneous determination of cholic acid and chenodeoxycholic acid pool sizes and fractional turnover rates. After oral administration of known amounts of 11,12-dideuterated chenodeoxycholic acid and 2,2,4,4-tetradeuterated cholic acid, the ratios of chenodeoxycholic acid-D2/chenodeoxycholic acid and cholic acid-D4/cholic acid are measured in consecutive serum samples, after which fractional turnover rates and pool sizes of chenodeoxycholic acid and cholic acid are determined arithmetically. In 7 healthy volunteers pool sizes for chenodeoxycholic acid and cholic acid were 22.9 +/- 7.8 and 24.1 +/- 11.7 mumol/kg, respectively. The corresponding values for the fractional turnover rates were 0.23 +/- 0.10 and 0.29 +/- 0.12/day. After oral administration of the labelled bile acids in capsule, the obtained pool sizes were significantly higher than after administration in a bicarbonate solution. Bile acid kinetics were also performed in a patient suffering from a cholesterol synthesis deficiency and in a patient very likely suffering from a bile acid synthesis deficiency. Furthermore, the kinetics of the intestinal absorption and hepatic clearance of unconjugated bile acids have been investigated in 2 healthy subjects.     

Serum bile acid profile in thyroid dysfunction and effect of medical treatment

1. Serum non-esterified bile acid profile was examined in patients with thyroid dysfunction. Sixteen hyperthyroid patients, six hypothyroid patients, nine patients taking thyroid or antithyroid drugs and 26 healthy controls were studied. The medicated patients were euthyroid when serum samples were collected. Bile acid concentration was determined by the simplified microassay method involving mass fragmentation spectrometry. 2. The sum of the concentrations of the individual bile acids was not significantly different among the four groups. However, the composition of bile acid reflected the thyroid function. The most prominent bile acid was deoxycholic acid in the hypothyroid patients and chenodeoxycholic acid in the hyperthyroid patients. The serum bile acid profile of medically treated patients was similar to that of normal controls. The ratio of the sum of deoxycholic and cholic acid to that of lithocholic and chenodeoxycholic acid was found to be a good indicator of thyroid function, while the ratio of cholic acid to chenodeoxycholic acid correlated poorly with it. 3. The characteristic effect of thyroid hormone on the serum bile acid composition in man was the shift from the 'family' of cholic acid to that of chenodeoxycholic acid. This is in agreement with experimental results in the rat, and suggests a specific action of thyroid hormone on the hydroxylating enzymes involved in the conversion of cholesterol into bile acids.     

Composition and role of short chain fatty acids in feces and peripheral blood serum of patients with cholelithiasis

Gas-liquid chromatography was used to estimate content of short-chain fatty acids (SCFA) in 25 patients with cholelithiasis, 32 patients with irritable colon syndrome and constipation (ICS) and 35 healthy subjects. It was found that SCFA absolute and relative concentration in the feces of cholelithiasis patients is abnormal indicating disturbance of microbiocenosis as shown by changes in functional activity of some anaerobes of the intestinal microflora participating in enterohepatic circulation of bile acids. Alterations of SCFA content in the serum of cholelithiasis patients may be related to steroids disbolism. The study of SCFA in the feces and peripheral blood serum from cholelithiasis patients is of diagnostic value.     

The nature of urinary bile acid conjugates in patients with extrahepatic cholestasis

Urinary bile acids from patients with extrahepatic cholestasis were extracted with Sep-pak C18 cartridges and group separated on diethylaminohydroxypropyl Sephadex LH-20. The nature of the different conjugates of cholic and chenodeoxycholic acid in the fractions was studied after further separation by preparative thin-layer chromatography. The free and glycine-conjugated bile acids were quantified by capillary gas chromatography and identified by gas chromatography-mass spectrometry (GC/MS). Taurine conjugates were split with cholylglycine hydrolase and the liberated free bile acids analysed by GC/MS. Sulphate esters were hydrolysed with Helix pomatia and the resulting bile acid derivatives were analysed as above. After hydrolysis with cholylglycine hydrolase, the glucuronides of the unconjugated bile acids were separated and identified by GC/MS. Amino acid analysis of the different fractions revealed that glycine and taurine were the only amino acids present in connection with cholic and chenodeoxycholic acid. Large amounts of monosulphated bile acid conjugates were present but no disulphates. Only 3-sulphates were found. Both sulphates and glucuronides were found exclusively as glycine or taurine conjugates and no such derivatives of unconjugated bile acids were isolated. The isolated conjugates were split either by a combination of acid solvolysis and alkaline hydrolysis or by Helix pomatia and cholylglycine hydrolase.     

Bile acid synthesis and excretion following release of total extrahepatic cholestasis by percutaneous transhepatic drainage

Abstract. Urinary, biliary and serum bile acids were studied in three patients before and after percutaneous transhepatic drainage for total bile duct obstruction.
Before drainage high urinary excretion often different bile acids occurred. The percentage distribution was: cholic and chenodeoxycholic acid (66–86%), hyo-cholic (3–16%), 3β 12α-dihydroxy-5-cholenoic (3–6%) and 3β-hydroxy-5-cholenoic acid (2–8%). These acids were regularly found in serum. In addition small amounts (less than 2%) of norcholic, allocholic, 3β, 7α-dihydroxy-5β-cholanoic, 3α, 7α-dihydroxy-5α-cholanoic and lithocholic acid were excreted in urine. Trace amounts of these bile acids were found in serum.
After start of drainage biliary bile acid excretion increased rapidly during the first day, dropped to a minimum during the second or third day and then slowly increased again. In spite of normal volumes of bile produced, the total serum bile acids and the urinary excretion of bile acids remained increased during a drainage period of 19 days. The bile acids were of the same type as observed during cholestasis. In serum the increase was mainly due to high concentrations of chenodeoxycholic and 3β-hydroxy-5-cholenoic acid, as sulphate esters.
Glycine and taurine conjugates of cholic, chenodeoxycholic and hyocholic acid were mainly excreted in bile. Bile acid sulphate esters were only present in trace amounts in bile and were mainly excreted in urine. This, combined with low renal clearance, explains the elevated serum levels of sulphate esters of chenodeoxycholic and 3β-hydroxy-5-cholenoic acid conjugates.