熊去氧胆酸的微生物转化条件及其制备

从416株泡木贼镰刀菌中,筛选出一株92-5菌株,它能在30℃转化石胆酸为熊去氧胆酸.研究了该菌株的最适转化条件,在该条件下,熊去氧胆酸的重量收率为42.3%.建立了适于工业化生产的产物分离制备方法.     

牛磺熊去氧胆酸的合成进展

牛磺熊去氧胆酸是由熊去氧胆酸的羧基和牛磺酸的氨基之间缩水而形成的结合型胆汁酸。主要介绍了目前四种牛磺熊去氧胆酸合成方法,并对四种方法的优缺点进行了全面的评价,从而为牛磺熊去氧胆酸的合理开发和利用提供思路。     

三株梭菌通过生物转化形成熊去氧胆酸的研究

用改进的薄层层析法定量测定了三株厌氧梭菌——产气荚膜梭菌(Clostridium perfr-ingens)HS-10、丁酸梭菌(C.butyrium)DL-20和LQ-29形成熊去氧胆酸(UDCA)的生物转化能力,并用正交法确定了HS-10菌株的最佳转化条件。发现该菌株在含O．2mmol／L鹅去氧胆酸(CDCA)的RCM培养基中培养6-48小时内,UDCA转化率均在80％以上。而且,当CDCA的浓度高达0．8-1．0 mmol／L时,其转化率仍在70％以上。此外,还初步发现未加任何营养成分的豆腐废水也可作为良好的转化培养基。本文是这两种菌能单独将CDCA 转化为UDCA的首次报道。     

熊去氧胆酸治疗原发性胆汁性肝硬化临床观察

目的探讨熊去氧胆酸治疗原发性胆汁性肝硬化的临床效果。方法选取某医院于2014年7月至2015年7月收治的原发性胆汁性肝硬化患者98例作为临床研究对象,随机将患者分为观察组和对照组,每组49例。两组患者均给予基础治疗,之后对照组患者采用通胆汤进行治疗,观察组患者在对照组的基础上加用熊去氧胆酸进行治疗。比较两组患者的治疗效果。结果根据分析结果,观察组患者的完全反应率明显高于对照组,并且肝功能指标明显优于对照组,比较结果具有显著差异性(P0.05)。结论熊去氧胆酸治疗原发性胆汁性肝硬化的临床效果良好,值得推广使用。     

肝纤维化程度及自身抗体表达对熊去氧胆酸单药治疗自身免疫性肝病重 叠综合征患者临床疗效的影响

目的:肝纤维化程度及自身抗体表达对熊去氧胆酸单药治疗自身免疫性肝病重叠综合征患者临床疗效的影响。方法:回顾性收集2007年-2011年住院的20例做过肝穿活检的经熊去氧胆酸单药治疗达到满意效果的自身免疫性肝炎和原发性胆汁性肝硬化重叠综合征患者的临床资料。结果:20例患者中,12例患者(60%)的肝穿标本活检评估处于肝纤维化S3或S4期,其初诊时基线特征与肝纤维化处于S0-S2期的患者基线特征无统计学差异。此外,该20例患者的血清抗平滑肌抗体的阳性率较低(1/20)。结论:肝脏纤维化程度不会引起熊去氧胆酸治疗效果的下降。     

思美泰联合熊去氧胆酸对妊娠期肝内胆汁淤积症患者的影响

目的:探讨思美泰联合熊去氧胆酸对妊娠期肝内胆汁淤积症患者的影响。方法:选取我院2015年2月至2016年2月收治妊娠期肝内胆汁淤积症患者共94例,按随机法分为观察组(47例)对照组(47例)。对照组采用思美泰+地塞米松,观察组采用思美泰+熊去氧胆酸。观察两组患者治疗前后血清总胆汁酸(TBA)、总胆红素(TB)、丙氨酸转氨酶(ALT)、门冬氨酸转氨酶(AST)、瘙痒评分及妊娠结局、围生儿情况。结果:治疗后,两组患者TBA、TB、ALT及AST、瘙痒评分水平均较治疗前下降,观察组下降更明显,差异具有统计学意义(P0.05);观察组患者早产率19.15%(9/47)、剖宫产率27.66%(13/47)、羊水污染率10.64%(5/47)及胎儿窘迫率12.77%(6/47)均分别显著低于对照组40.43%(19/47)、57.45%(27/47)、21.28%(10/37)、19.15%(9/47),其中早产率及剖宫产率比较差异具有统计学意义(P0.05)。结论:思美泰联合熊去氧胆酸能明显改善妊娠期肝内胆汁淤积症患者胆汁酸、肝酶水平及妊娠结局。     

熊去氧胆酸对婴儿肝炎综合征患儿血清炎症因子和肝功能的影响*

目的:探讨熊去氧胆酸对婴儿肝炎综合征患儿血清炎症因子和肝功能的影响。方法:选取我院自2013年5月-2015年5月收治的婴儿肝炎综合征患儿91例,随机分为对照组(n=47)和观察组(n=44),对照组患儿给予常规护肝、利胆等治疗,观察组患儿在对照组的基础上给予熊去氧胆酸治疗,两组均治疗3周。比较两组患儿治疗前后的血清炎症因子及肝功能指标水平,观察两组患儿用药后的临床治疗效果及不良反应发生情况。结果:治疗后,所有患儿的血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、总胆红素(TBil)、直接胆红素(DBil)、丙氨酸转氨酶(ALT)、谷氨酰转肽酶(GGT)、总胆汁酸(TBA)水平均低于治疗前,且观察组低于对照组(P0.05)。观察组患儿治疗后总有效率高于对照组(P0.05)。两组患儿总不良反应发生率比较差异无统计学意义(P0.05)。结论:熊去氧胆酸可以减轻婴儿肝炎综合征患儿的炎症反应,改善其肝功能,疗效显著且安全性好。     

熊去氧胆酸联用思美泰对妊娠期肝内胆汁淤积症重症患者瘙痒程度、妊娠结局及肝功能的影响

目的:探讨熊去氧胆酸联用思美泰对妊娠期肝内胆汁淤积症(ICP)重症患者瘙痒程度、妊娠结局及肝功能的影响。方法:选取2016年6月到2017年12月期间在我院接受治疗的ICP重症患者76例,根据随机数字表法将患者均分为研究组(n=38)和对照组(n=38)。对照组采用熊去氧胆酸进行治疗,研究组采用熊去氧胆酸联用思美泰进行治疗。比较两组患者治疗前、治疗7d后的Ribaha皮肤瘙痒程度评分、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆汁酸(TBA)、血清总胆红素(TB)的水平,比较两组患者的妊娠结局。结果:治疗7d后两组患者的瘙痒程度评分均明显降低,且研究组低于对照组(P0.05)。治疗7d后两组患者的AST、ALT、TBA、TB水平均明显降低,且研究组患者的AST、ALT、TBA、TB水平低于对照组,差异有统计学意义(P0.05)。两组患者的新生儿窒息发生率和新生儿体质量比较无统计学差异(P0.05),研究组患者早产、胎儿窘迫、羊水胎粪污染的发生率低于对照组,差异有统计学意义(P0.05)。结论:熊去氧胆酸联用思美泰可有效缓解ICP重症患者的瘙痒程度,改善肝功能和妊娠结局,临床疗效显著,具有积极的临床意义。     

丁二磺酸腺苷蛋氨酸联合熊去氧胆酸对妊娠期肝内胆汁淤积症患者肝功能及妊娠结局的影响

目的:探讨丁二磺酸腺苷蛋氨酸联合熊去氧胆酸对妊娠期肝内胆汁淤积症(ICP)患者肝功能及妊娠结局的影响。方法:选取2016年1月至2017年10月我院接诊的96例ICP患者,按照随机数字表法分为观察组和对照组,每组各48例,两组患者均给予常规基础治疗,对照组在此基础上给予熊去氧胆酸治疗,观察组在对照组基础上给予丁二磺酸腺苷蛋氨酸治疗,比较两组患者瘙痒、黄疸改善时间及治疗前后胆酸和肝功能指标检测结果,观察并对比两组母婴预后情况。结果:观察组瘙痒改善时间及黄疸改善时间均低于对照组(P0.05)。两组患者治疗前总胆汁酸(TBA)、甘胆酸(CG)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBiL)、直接胆红素(DBiL)水平对比差异无统计学意义(P0.05);两组患者治疗后TBA、CG、ALT、AST、TBiL、DBiL水平均低于治疗前,且观察组低于对照组(P0.05)。观察组羊水污染、胎儿窘迫、早产、剖宫产及新生儿Apgar评分7分发生率均低于对照组(P0.05),两组患者产后出血、死胎发生率对比差异无统计学意义(P0.05)。结论:丁二磺酸腺苷蛋氨酸联合熊去氧胆酸能够有效改善ICP症状和肝功能,降低不良母婴预后发生风险,可作为优选治疗方案。     

原发性胆汁性肝硬化的药物治疗进展

原发性胆汁性肝硬化(Primary Biliary Cirrhosis,PBC)是一种以胆汁淤积及慢性非化脓性破坏性胆管炎为特点的自身免疫介导的慢性肝脏病。熊去氧胆酸(UDCA)作为PBC患者的首选治疗药物可使患者的生化指标、存活指标以及组织学等都得以改善。尽管如此,PBC的治疗仍是临床医师的一大难题,大约40%的PBC患者对UDCA的治疗仅获得了不完全应答,而肝移植则为晚期PBC患者治疗之首选。本文简要介绍近些年治疗PBC药物的新进展,包括熊去氧胆酸、布地奈德、免疫抑制剂、贝特类、6α-乙基鹅去氧胆酸、利妥昔单抗以及抗逆转录病毒药物等,期望为PBC的治疗提供帮助。     

BILIARY BILE ACID COMPOSITION OF THE PHYSETERIDAE (SPERM WHALES)

Abstract: The bile acid composition of bile obtained from the hepatopancreatic ducts of three species of sperm whales (Cetacea: Physeteridae) was investigated. Bile acids were isolated by adsorption chromatography and analyzed by sequential HPLC, SIMS, and GLC-MS. In each species the dominant bile acids were deoxycholic acid (a secondary bile acid formed by bacterial 7α-dehydroxylation of cholic acid), and chenodeoxycholic acid (a primary bile acid) which together composed more than 86% of biliary bile acids in all three species. In Physeter catodon (sperm whale) deoxycholic acid constituted 79%, and in Kogia breviceps (pygmy sperm whale) it was 61% of biliary bile acids. The sperm whale, which differs from other whales in having a remnant of a large intestine, is the second mammal identified to date in which deoxycholic acid is the predominant bile acid. The high proportion of deoxycholic acid indicates that in the Physeteridae, anaerobic fermentation occurs in its cecum, and that bile acids undergo enterohepatic cycling. Also found were minor proportions of cholic acid, as well as bacterial derivatives of chenodeoxycholic acid (ursodeoxycholic acid, lithocholic acid, and the 12β-epimer of allo-deoxycholic acid). Bile acids were conjugated with taurine in all species; however, in the sperm whale ( Physeter ) glycine conjugates were present in trace proportions. The bile acid hydroxylation pattern (12α- but not 6α-hydroxylation), lack of primary 5α- (allo) bile acids, and presence of glycine conjugated bile acids suggests the possibility that sperm whales originated from ancient artiodactyls.     

Adsorption of Lithocholic Acid to Fusarium equiseti M41 as an Essential Process in Its Conversion to Ursodeoxycholic Acid

Fusarium equiseti M41 converts lithocholic acid to ursodeoxycholic acid. Adsorption of lithocholic acid particles to mycelia of F. equiseti M41 is essential in the conversion of lithocholic acid to ursodeoxycholic acid. Production of ursodeoxycholic acid was negligible when particles of lithocholic acid were absent. As the concentration of lithocholic acid particles increased, both the amount of mycelium-bound lithocholic acid and the production of ursodeoxycholic acid increased hyperbolically (K_1/2 = 1.9 g/liter and K_mapparent = 1.9 g/liter. A fluorescent lithocholic acid derivative was used to confirm that insoluble particles of lithocholic acid attached to the surface of the mycelia. The hydrophobic nature of this binding was estimated from the close relationship observed between the hydrophobicity of bile acids and their binding capacity to the mycelia. By repeated washing with 30% dimethyl sulfoxide, two binding modes of lithocholic acid were distinguished, i.e., surface binding (59% of bound lithocholic acid) and tight binding (41% of bound lithocholic acid). From the amount of tightly bound lithocholic acid, the intracellular concentration of lithocholic acid was calculated to be 1,433-fold higher than its saturating concentration in the reaction mixture, thus promoting effective conversion to ursodeoxycholic acid in the mycelia. Several lines of evidence indicated that glycoproteins of the cell wall participated in the binding of lithocholic acid.     

Synthesis and proteasome inhibition of lithocholic acid derivatives

A new class of proteasome inhibitors was synthesized using lithocholic acid as a scaffold. Modification at the C-3 position of lithocholic acid with a series of acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them, the phenylene diacetic acid hemiester derivative (13) displayed the most potent proteasome inhibition with IC₅₀ = 1.9 μM. Enzyme kinetic analysis indicates that these lithocholic acid derivatives are noncompetitive inhibitors of the proteasome.     

Isolation and chemical synthesis of a major, novel biliary bile acid in the common wombat (Vombatus ursinus): 15alpha-hydroxylithocholic acid

The major bile acids present in the gallbladder bile of the common Australian wombat (Vombatus ursinus) were isolated by preparative HPLC and identified by NMR as the taurine N-acylamidates of chenodeoxycholic acid (CDCA) and 15alpha-hydroxylithocholic acid (3alpha,15alpha-dihydroxy-5beta-cholan-24-oic acid). Taurine-conjugated CDCA constituted 78% of biliary bile acids, and (taurine-conjugated) 15alpha-hydroxylithocholic acid constituted 11%. Proof of structure of the latter compound was obtained by its synthesis from CDCA via a Delta14 intermediate. The synthesis of its C-15 epimer, 15beta-hydroxylithocholic acid (3alpha,15beta-dihydroxy-5beta-cholan-24-oic acid), is also reported. The taurine conjugate of 15alpha-hydroxylithocholic acid was synthesized and shown to have chromatographic and spectroscopic properties identical to those of the compound isolated from bile. It is likely that 15alpha-hydroxylithocholic acid is synthesized in the wombat hepatocyte by 15alpha-hydroxylation of lithocholic acid that was formed by bacterial 7alpha-dehydroxylation of CDCA in the distal intestine. Thus, the wombat appears to use 15alpha-hydroxylation as a novel detoxification mechanism for lithocholic acid.     

仙草中的一个五环三萜酸分离提取及鉴定

从仙草（Ｍｅｓｏｎａ Ｃｈｉｎｅｎｓｉｓ Ｂｅｎｔｈ）中分离提取到一种化合物,经红外光谱、核磁共振及质谱等测试分析,该仙草提取物既不是熊果酸（ｕｒｓｏｌｉｃ ａｃｉｄ）,也非齐墩果酸（ｏｌｅａｎｏｌｉｃａｃｉｄ）而是一种与它们结构极为相似的五环三萜酸化合物。     

十三烷1,13—二羧酸的发酵研究

热带假丝酵母(C.tropicalis)NP-6-126是经过紫外线和亚硝酸反复诱变筛选培育出来的,它是生产十三烷1,13一二羧酸(DC_(15)的优良生产突变株,尿素和硝酸钾浓度对其产酸有明显影响。尿素浓度在0.15％～0.21％范围内对产酸有利,尤其是0.18％最佳,浓度增大,明显抑制DC_(15)的产生和积累;硝酸钾的加入,也明显促进DC_(15)产量的提高,0.6％～0.9％硝酸钾浓度较合适。于16L自动控制罐发酵7d,DC_(15)达到130g/L,放大到2500L罐,在最佳条件下,连续5批,发酵6d,DC_(15)产量平均达到176g/L,正十五烷(nC_(15)转化率平均为52.5％,后处理总收率平均为80.6％,DC_(15)的纯度平均为95.83％。     

从大肠杆菌C-8制备和纯化唾液酸

大肠杆菌产生的多聚唾液酸是一类线性的同聚合体,这由２００个左右的唾液酸通过α２,８酮苷键连接。我们在前文［１］中已就产多聚唾液酸的菌种筛选及产酸条件作了叙述。本文将对多聚唾液酸的水解、唾液酸的纯化及鉴别进行研究,为今后应用打下基础。１材料和方法１...     

Studies in the rat on the hepatic subcellular distribution and billary excretion of lithocholic acid.

1. A compartmental model has been used to derive the in vivo subcellular distribution of lithocholic acid in rat liver. The model is based on the values of the partition coefficients for the distribution of lithocholic acid between subcellular fractions and buffer. It also permits calculation of the amount of lithocholic acid which is in free solution in cytosol. 2. The hypothesis that the rate of biliary excretion of a bile acid depends on the proportion in free solution was investigated by comparing the rates of biliary excretion of lithocholic acid and glycocholic acid. The rate for lithocholic acid was substantially less than for glycocholic acid while the percentages of each bile acid in free solution were 0.8% and 10%, respectively. 3. The validity of the model was supported by the observation that the amounts of lithocholic acid predicted to be present in the nuclear and cytosolic fractions were similar to the amounts found after intravenous injection of the bile acid.     

维生素在丙酮酸过量合成中的重要作用

研究了烟酸、硫胺素、吡哆醇、生物素和核黄素对一株光滑球拟酵母(\%Torulopsis glabrata\%) WSH\|IP303以葡萄糖为碳源、以氯化铵为唯一氮源生产丙酮酸的影响。利用正交试验方法,确证了硫胺素是影响WSH\|IP303生产丙酮酸的最重要因素。在硫胺素浓度一定(0.01～0.015mg/L)的前提下,提高烟酸浓度有助于加快耗糖速度。当烟酸、硫胺素、吡哆醇、生物素和核黄素的浓度分别为8、0.015、0.4、0.04和01mg/L时,摇瓶发酵48h,丙酮酸产量和产率可分别达到52.4g/L和0525g/g。采用优化的维生素组合方式,进行2.5L罐分批发酵,在初糖浓度120g/L的条件下发酵57.5h,丙酮酸产量和产率分别达到69.4g/L和0593g/g,分别比摇瓶培养的最好结果提高了32.%和13%。