动物胆汁酸代谢与肠道微生态的互作关系

胆汁酸代谢与肠道微生态密切相关,胆汁酸在肝脏中由胆固醇合成,并通过肠道微生物群进一步代谢,主要存在于肠肝循环中并具有重要调节作用。同时,胆汁酸作为重要的信号分子,其与FXR、FGFR4和TGR5等多种胆汁酸相关受体结合,能有效调节肠道菌群,维持肝肠循环稳态,而肠道菌群的变化直接影响FXR、FGF15等相关基因的表达,进而影响胆汁酸代谢。本文综述了胆汁酸代谢与肠道微生态之间的双向调控机制,进一步明确了二者之间的相互作用关系,为解决动物肝肠胆相关疾病提供科学理论。     

有机溶质转运体α-β在动物胆汁酸代谢中的作用

有机溶质转运体α-β(OSTα-OSTβ)是影响胆汁酸代谢的关键因子之一，其主要通过转运胆汁酸，活化法尼醇X受体（FXR），激活胆固醇7α-羟化酶（CYP7A1）途径，调控胆汁酸合成量。且OSTα-OSTβ表达缺失时，胆汁酸合成减少，脂质吸收率降低，对胰岛素信号传导的损伤减轻，维持胰岛素敏感性，改善机体健康状况。本文就OSTα-OSTβ对动物胆汁酸的调控作用进行综述，旨在为OSTα-OSTβ在畜牧生产中的应用提供参考。     

胆汁酸的肠肝循环及胆汁酸受体在糖脂代谢中的调控作用

胆汁酸是胆汁的主要成分,在体内以多种形式存在。随着对胆汁酸研究的深入,学者们发现胆汁酸是体内的一种重要的信号分子,通过介导胆汁酸受体而发挥相应的生物学效应。肠肝循环是指胆汁酸合成、分泌、排泄、再吸收的循环过程。近年来研究发现胆汁酸与其受体结合后,可以调控胆汁酸的肠肝循环过程,进而调节糖脂代谢。本文针对胆汁酸的肠肝循环以及胆汁酸受体在糖脂代谢中的调控作用进行综述,以期为今后探究胆汁酸及其受体在代谢相关疾病防治中的作用提供有价值的参考。     

牛磺鹅去氧胆酸对动物免疫的调控作用及其营养调控研究进展

牛磺鹅去氧胆酸（TCDCA）作为胆汁酸（BA）活性物质之一，其可通过激活G蛋白偶联受体5(TGR5)/糖皮质激素受体（GR）相关通路降低促炎因子和增加抗炎因子表达量，发挥抗炎作用。TCDCA在肠道菌群作用下解离为鹅去氧胆酸后与法尼醇X受体（FXR）结合，负反馈调节BA合成，减少胆汁淤积，减轻炎症。此外，运用营养手段调控肠肝轴TCDCA含量将改善动物的糖脂代谢、热应激、肝损伤及生长水平。因此，本文重点综述TCDCA作用于TGR5、GR和FXR相关通路对动物免疫的调节机制及其营养调控研究进展，为TCDCA预防和治疗动物疾病提供参考。     

胆汁酸对动物炎性肠病通路的影响及其在畜禽生产中的应用前景

胆汁酸(BA)作为胆汁的重要成分之一,在动物炎性肠病(IBD)中发挥重要作用.过多BA在肠道内聚积是引发IBD的原因之一.作为体内的一种重要信号分子,BA能激活法尼醇X受体(FXR)和G蛋白胆汁酸偶联受体5(TGR5),发挥相应生物学功能,既在一定程度上保护肠道免受BA聚积产生的危害,又对IBD具有缓解作用.本文综述了...     

外源性胆汁酸对畜禽抗热应激作用研究进展

胆汁酸作为胆汁的重要成分,在促进营养吸收、保障畜禽健康方面具有重要作用。胆汁酸通过非受体介导途径与极性磷脂分子结合乳化脂类以促进脂类和脂溶性物质吸收,作为关键的信号分子激活特异受体和细胞信号通路,促进糖和脂肪代谢稳态,保护肠道屏障和抗应激损伤。近年来,外源性胆汁酸对缓解热应激导致的负面影响,诸如胰岛素抵抗、脂肪堆积、肠道屏障受损、氧化应激等作用逐渐受到关注。本文系统地对胆汁酸代谢进行了综述,详细总结了胆汁酸对机体的调控机制,以期对外源性胆汁酸缓解生长阶段猪和肉鸡热应激的理论研究与应用提供参考。     

胆汁酸调控S1PR2通路在动物炎症中的作用研究进展

胆汁酸(BAs)作为1-磷酸鞘氨醇受体2(S1PR2)上游激活物之一,可直接调控S1PR2活性,也可通过BAs相关信号通路法尼醇X受体(FXR)和G蛋白胆汁酸偶联受体5(TGR5)介导S1PR2途径.S1PR2通过平衡核因子Kappa B(NF-κB)与c-Jun氨基末端激酶(JNK)信号转导通路,调节动物体炎症.本文...     

糖皮质激素对鸡胚肝细胞脂肪和胆汁酸代谢相关基因表达的影响

为揭示应激导致家禽肝脏代谢异常的机理,本研究探查了糖皮质激素——地塞米松(DEX)对鸡胚肝细胞脂肪和胆汁酸代谢相关基因表达的影响。选取19胚龄的无特定病原体(SPF)鸡蛋,原代培养鸡胚肝细胞(37℃、5%CO2),用0(对照)、200、500、1 000 nmol/L的地塞米松分别处理24 h。结果表明:与对照组相比,高剂量(500、1 000 nmol/L)地塞米松处理显著降低了脂肪代谢相关基因——脂肪酸转运蛋白1 (FATP-1)、固醇调节元件结合蛋白-1C(SREBP-1C)、载脂蛋白B100(APOB100)、肝脏X受体(LXR)以及胆汁酸摄取相关基因Na+/牛磺胆盐共转运体(NTCP)的mRNA相对表达水平(P0.05),显著提高了胆汁酸排出相关基因——胆盐输出泵(BSEP)的mRNA相对表达水平(P0.05);低剂量(200 nmol/L)地塞米松处理显著提高胆汁酸合成相关基因——胆固醇7-羟化酶(CYP7A1)和法尼酯X受体(FXR)的mRNA相对表达水平(P0.05),同时,SREBP-1C的mRNA相对表达水平显著降低(P 0.05),BSEP的mRNA相对表达水平显著上升(P0.05)。由此得出,高剂量糖皮质激素对鸡胚肝细胞的脂肪合成、转运和胆汁酸的摄取具有抑制作用;低剂量糖皮质激素可以促进胆汁酸的合成和排出,部分反应具有剂量依赖性。     

铜肠道稳态平衡调控机制研究进展

铜是动物机体必需的微量元素之一,肠道细胞内铜的吸收、储存、释放、转运对肠道铜稳态的维护至关重要,肠道铜稳态的失衡使肠道细胞脱落导致肠道功能障碍。随着对肠道铜转运因子与靶细胞器研究的逐步深入和完善,人们取得了新的发现和认识。作者综述了胞内的线粒体、高尔基体、胞浆分别与铜伴侣蛋白、铜转运蛋白的结合途径,阐明了铜特异性转运蛋白（CTR1）的表达机制,铜转出蛋白（ATP7A、ATP7B）在高铜情况下的再分配机制及其他上皮细胞组织铜的稳态机制。根据以上机制得出,肠细胞亚细胞器的铜转运蛋白的表达位置和表达水平随其内环境铜水平的变化而趋于肠稳态形式变化。此结论为揭示肠道铜稳态机制提供了一定的理论依据。     

胆汁酸的作用与分子调控机制

很多研究表明,胆汁酸能够促进肠道中胆固醇、脂质和脂溶性维生素的吸收。除此之外,胆汁酸还是一个重要的信号调节分子,能够激活肝脏和胃肠道细胞中特异性核受体、G蛋白偶联受体以及细胞信号传导通路,从而改变与编码调控胆汁酸、葡萄糖、脂肪酸和脂蛋白的合成、代谢、运输以及能量代谢的相关酶(蛋白)的基因表达。文章详细论述了胆汁酸的作用以及胆汁酸作为信号分子的调控机制。     

Bile acid fractionations by high-performance liquid chromatography in equine liver disease

Serum bile acids were fractionated by high-performance liquid chromatography (HPLC) in 13 control and 8 cases of liver disease in horses. The severity and type of liver injury was determined by histopathological examination of biopsy and/or necropsy specimens. The total serum bile acids (tSBA) were determined in these horses by an enzymatic method (SBA-EA) and by summation of the bile acids (SBA-LC) as fractionated by the HPLC. The SBA-LC were generally higher than the SBA-EA in both the controls and liver disease and they did not parallel each other. The primary bile acids, total cholates and total chenodeoxycholates accounted for most of the tSBA increases in liver disease. There was a shift in profile from taurocholate to free (unconjugated) cholate in direct relation to the severity of the liver injury. Among the secondary bile acids, total deoxycholates and total taurodeoxycholates increased at random. The pattern of the SBA profile in relation to the severity of the liver disease suggested that hepatocellular excretion is the most sensitive step in the enterohepatic circulation of the bile acids.     

Effects of halothane anesthesia on equine liver function

Effects of halothane anesthesia were investigated in ponies prepared surgically with chronic external biliary fistulas (T tubes) to determine the effects on liver function and biliary excretion during 2 hours of anesthesia. Four studies were performed on 2 ponies, 2 to 6 months after surgery with the enterohepatic circulation held intact between studies. Intravenous bile acid infusion was used to maintain steady-state bile flow, bilirubin, and bile acid excretion during each study. Compared with the immediate 2-hour preanesthesia values (base line), halothane caused a 138% increase in bilirubin excretion, a 60% increase in biliary bilirubin concentration, and a 43% increase in PCV. Halothane anesthesia also caused a 16% reduction in plasma bilirubin, a 46% reduction in biliary bile acid concentration, and a 27% reduction in bile acid excretion. The bile acid independent fraction of bile flow appeared to increase. Plasma aspartate transaminase concentration did not change during anesthesia. The ratio of conjugated bilirubin fractions in bile [82% to 83% disconjugates of glucuronide and glucoside (2 forms) and 17% to 18% monoconjugates of glucoside, glucuronide, and xyloside] did not change during anesthesia and less than 1% was excreted unconjugated. Halothane anesthesia did not appear to affect adversely the activity of the transferase-conjugating enzymes in the presence of an increased bilirubin load. Seemingly, greatly increased conjugated bilirubin excretion observed during halothane anesthesia was most likely the result of a combination of increased hepatic clearance from plasma and increased hepatic bilirubin production from turnover of free hepatic heme or heme from the induced cytochrome P-450 system.(ABSTRACT TRUNCATED AT 250 WORDS)     

The utility of uric acid assay in dogs as an indicator of functional hepatic mass

Uric acid was used as a test for liver disease before the advent of enzymology. Three old studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine metabolism in the liver, deserved re-evaluation as a liver function test. Serum totalbile acids are widely accepted as the most reliable liver function test. This study compared the ability of serum uric acid concentration to assess liver function with that of serum pre-prandial bile acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also compared in a renal disease group. Using a control group of healthy dogs, a group of dogs with congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was compared to detect reduced functional hepatic mass overall and in the vascular or parenchymal liver disease groups separately. Sensitivities, specificities and predictive value parameters were calculated for each test. The medians of uric acid concentration did not differ significantly between any of the groups, whereas pre-prandial bile acids medians were significantly higher in the liver disease groups compared with the normal and renal disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65% while the specificity of uric acid in detecting liver disease overall was 59%. The sensitivity and specificity of uric acid in detecting congenital vascular liver disease was 68% and 59%, respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver disease was 63% and 60%, respectively. The overall positive and negative predictive values for uric acid in detecting liver disease were poor and the data in this study indicated uric acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due to its renal route of excretion.     

The effect of copper and heliotrope on the composition of bile in sheep

The effects of interrupting the enterohepatic circulation (EHC) of bile salts for seven hours and of feeding copper and heliotrope alone and combined for 13 weeks, on bile flow and excretion of copper, zinc, iron and alpha-mannosidase were studied in sheep. Interruption of EHC reduced bile flow rate and increased the concentration of copper, zinc, iron and bile acids while alpha-mannosidase's activity remained stable. Changes in concentration were related to changes in bile volume for copper and zinc only. Total output per hour was not changed. Biliary concentration of copper correlated with alpha-mannosidase's activity in control sheep and those given copper or heliotrope, supporting the hypothesis that lysosomes are involved in biliary secretion of copper in sheep. Increasing the intake of copper increased the rate of excretion of copper in bile. Copper output was lower when heliotrope was fed alone.     

Plasma 14C-cholic acid clearance in healthy dogs and dogs with cholestasis or a congenital portosystemic shunt

The clearance profiles of intravenously injected tracer doses of radioactively labelled cholic acid were investigated in healthy dogs, dogs with a congenital portosystemic shunt and dogs with cholestasis. The rate constants and residual plasma activity were significantly different in the healthy and diseased dogs, but it was not possible to differentiate between the dogs with portosystemic shunting and cholestasis because the results were determined not only by factors involved in plasma bile acid clearance but also by the enterohepatic circulation.     

丁酸对乳腺组织基因表达的调控作用及其机制

丁酸是重要的短链脂肪酸,可作为信号分子结合其受体在机体发挥一些重要的生理作用,如调节乳腺、肝脏及脂肪组织的脂质代谢。丁酸的作用机制是多方面的,其中许多机制与其参与基因表达的调控作用有关。丁酸不仅调节某一个基因的表达,还参与信号通路及基因网络的调节。本文综述了丁酸作为重要的乳成分合成前体物、组蛋白去乙酰酶(DHAC)抑制剂、G蛋白偶联受体的配体对乳腺组织基因表达的调控作用及其相关机制。     

源于肠道菌群的γ-氨基丁酸对机体的调节机制

γ-氨基丁酸(γ-aminobutyric acid,GABA)作为中枢神经系统主要的抑制性神经递质,一直被认为在大脑中合成。但是,近年来的研究发现肠道菌群也能够产生GABA,并通过神经通路、血液循环和免疫等方面调节机体,在焦虑抑郁、内脏疼痛、功能性肠病和代谢性疾病中发挥不可忽视的作用。现从GABA作用于机体的不同途径出发,主要阐述了源于肠道菌群的GABA对机体的调节机制,为GABA、肠道菌群的基础研究以及临床、生产应用提供参考和依据。     

The pathophysiology and laboratory diagnosis of congenital portosystemic shunts in dogs

Abstract Congenital portosystemic shunts generally arise as single vascular anomalies that cause the portal blood to bypass the liver and enter the systemic venous circulation directly. The liver is primarily affected, as it is deprived of perfusion by portal hepatotrophic factors such as insulin, glucagon, and amino acids. There is progressive hepatic atrophy, and as a consequence, dysfunction. Hepatic encephalopathy can result from increased levels of ammonia and gamma-aminobutyric acid within the systemic circulation. Variably toxic amines, captans and short chain fatty acids may act as false neurotransmitters. Hypoglycaemia will exacerbate the effects of these substances. Increased concentrations of ammonia and uric acid in the urine predispose to the precipitation of ammonium biurate crystals and the formation of calculi. Haematological changes include anaemia, microcytosis, hypoproteinaemia, leucocytosis, and coagulation abnormalities. Gastrointestinal effects are common. They may be displayed as anorexia, vomiting, ptyalism, pica, diarrhoea, or polyphagia. Most dogs are less than 1 year of age at initial presentation. Diagnosis from a laboratory viewpoint will involve a consideration of the history, clinical findings, haematology, serum biochemistry and urinalysis. If the findings are suggestive of a congenital portosystemic shunt, the demonstration of elevated fasting or, more consistently, post-prandial serum bile acid concentrations, and subsequent histological examination of a liver biopsy will provide a definitive diagnosis.     

The pathophysiology and laboratory diagnosis of congenital portosystemic shunts in dogs

Congenital portosystemic shunts generally arise as single vascular anomalies that cause the portal blood to bypass the liver and enter the systemic venous circulation directly. The liver is primarily affected, as it is deprived of perfusion by portal hepatotrophic factors such as insulin, glucagon, and amino acids. There is progressive hepatic atrophy, and as a consequence, dysfunction.

Hepatic encephalopathy can result from increased levels of ammonia and gamma-aminobutyric acid within the systemic circulation. Variably toxic amines, captans and short chain fatty acids may act as false neurotransmitters. Hypoglycaemia will exacerbate the effects of these substances. Increased concentrations of ammonia and uric acid in the urine predispose to the precipitation of ammonium biurate crystals and the formation of calculi.

Haematological changes include anaemia, microcytosis, hypoproteinaemia, leucocytosis, and coagulation abnormalities. Gastrointestinal effects are common. They may be displayed as anorexia, vomiting, ptyalism, pica, diarrhoea, or polyphagia. Most dogs are less than 1 year of age at initial presentation.

Diagnosis from a laboratory viewpoint will involve a consideration of the history, clinical findings, haematology, serum biochemistry and urinalysis. If the findings are suggestive of a congenital portosystemic shunt, the demonstration of elevated fasting or, more consistently, post-prandial serum bile acid concentrations, and subsequent histological examination of a liver biopsy will provide a definitive diagnosis.