Farnesol作用变异链球菌脱矿的实验研究

目的 Farnesol(法尼醇)作为密度感应分子,具有影响变异链球菌生物膜代谢以及介导肿瘤细胞凋亡的作用。文中研究Farnesol对变异链球菌脱矿的影响。方法将变异链球菌UA159菌悬液接种于放置牙釉质切片的培养皿中,分为5组,即变链+0μmol/L Farnesol组、变链+50μmol/L Farnesol组、变链+100μmol/L Farnesol组、变链+200μmol/L Farnesol组和对照组。对照组中加入无菌去离子水。采用扫描电镜观察釉质表面的变异链球菌生物膜,显微硬度仪检测实验前后釉质表面显微硬度(surface microhardness,SMH),并用粗糙度仪测定釉面粗糙度。结果随着Farnesol浓度的递增,变异链球菌生物膜生长受抑制,釉质表面粗糙度减少,釉质显微硬度的下降幅度减小,当Farnesol浓度为200μmol/L时釉质显微硬度值[(270.87±12.19)N/mm2]较[变链+50μmol/L Farnesol组、变链+100μmol/L Farnesol组、变链+0μmol/L Farnesol组的(224.63±18.98)、(228.06±10.40)、(198.57±8.19)N/mm2]明显升高(P<0.01),各实验组的SMH较对照组[(368.60±7.33)N/mm2]低,差异有统计学意义(P<0.05)。结论 Farnesol可抑制变异链球菌对牙釉质的脱矿作用。

Farnesol对变形链球菌脱矿作用的体外研究

目的研究Farnesol(法尼醇)对变形链球菌脱矿作用的影响。方法 BHI培养变形链球菌,将常规预备好的牙釉质切片放置于菌悬液中。实验组分别加入浓度为0、50、100、200μmol/L的Farnesol,对照组中加入无菌去离子水。采用原子吸收分光光度法检测不同时间点(24、48及72 h)菌悬液中钙离子的浓度。结果随着Farnesol浓度的递增,菌悬液中钙离子浓度逐渐降低,当Farnesol浓度为200μmol/L时菌悬液中钙离子的浓度与其余3组相比有显著性差异,实验组与对照组相比也有显著性差异(P<0.05)。结论 Farnesol可抑制变形链球菌对牙釉质的脱矿作用。

Farnesol对白假丝酵母菌细胞生长及活性的干扰作用

目的:评价Farnesol对白假丝酵母菌生长、细胞活性及形态的干扰作用;检测氟康唑、克霉唑、制霉菌素、特比萘酚、卡泊芬净在不同浓度Farnesol条件下对白假丝酵母菌的抗菌活性。方法:通过吸光浊度测定不同浓度组Farnesol对白假丝酵母菌生长作用的影响;采用MTT法检测Farnesol对白假丝酵母菌细胞活性的干扰作用;光镜及电镜扫描观察不同浓度组Farnesol作用下,白假丝酵母菌细胞形态改变;测定不同种类抗真菌药物在不同浓度组Farnesol条件下对白假丝酵母菌的抗菌活性。结果:Farnesol对白假丝酵母菌的生长及细胞活性具有抑制作用。低浓度Farnesol即可抑制假丝酵母菌菌丝的形成,随着Farnesol浓度的升高,菌株以孢子相存在且生长受到抑制;高浓度组Farnesol并不能完全抑制菌株生长。Farnesol对抗真菌药物的抗菌活性具有干扰作用,低浓度Farnesol环境可以改善氟康唑的"拖尾"现象。结论:Farnesol对白假丝酵母菌生长及细胞活性具有浓度依赖性的抑制作用。Farnesol抑制白假丝酵母菌菌丝形成,可干扰抗真菌药物的活性,低浓度改善氟康唑的"拖尾"现象。

真菌密度感应分子 Farnesol 在表皮葡萄球菌和白假丝酵母菌混合生物膜形成中的作用

目的探讨真菌密度感应分子Farnesol在表皮葡萄球菌和白假丝酵母菌混合生物膜形成中的作用。方法将表皮葡萄球菌标准株ATCC35984及白假丝酵母菌标准株ATCC10231混合培养建立体外生物膜模型,加入Farnesol或不加入Farnesol分为Farnesol处理组和对照组,孵育2、4、6、8、12、24、48、72、96h时用结晶紫染色法半定量检测生物膜形成能力;二甲氧唑黄(XTT)比色法评价生物膜的体外生长动力学;扫描电子显微镜观察生物膜超微结构;荧光定量PCR分析各组生物膜形成相关基因的表达情况。结果结晶紫染色法生物膜半定量检测显示,12、24hFarnesol处理组和对照组差异有统计学意义(P<0.05)。XTT比色法生长动力学检测显示,Farnesol处理组在4、48h与对照组比较,差异有统计学意义(P<0.05)。扫描电镜结果显示,对照组混合生物膜结构较Farnesol处理组致密复杂。荧光定量PCR结果显示,培养6hFarnesol处理组表皮葡萄球菌生物膜形成相关基因icaA、fbe、aap基因及白假丝酵母菌生物膜形成相关基因als3、hwp1、efg1基因的表达下调;培养24hFarnesol处理组表皮葡萄球菌生物膜形成相关基因aap基因及白假丝酵母菌生物膜形成相关基因als3、hwp1、efg1基因的表达下调。结论在真菌密度感应分子Farnesol的干预下,对照组形成的混合生物膜较Farnesol处理组结构更为致密及复杂,这种结构的改变可能与Farnesol处理组白假丝酵母菌生物膜形成相关基因als3、hwp1、efg1基因的表达下调相关性更密切。

内源性Farnesol对变异链球菌脱矿作用的研究

目的观察内源性Farnesol处理变异链球菌后牙釉质脱矿的变化。方法放置牙釉质切片于培养皿中,实验分5组,前3组加入变异链球菌菌悬液的同时分别添加去离子水、白色念珠菌24 h上清、白色念珠菌菌悬液,第4组加入白色念珠菌菌悬液,去离子水组为空白对照组。采用原子吸收分光光度法检测不同时间点(24、48、72 h)菌悬液中钙离子的浓度。结果加入白色念珠菌24 h上清组在24、48、72 h分别测得钙离子的浓度为(80.26±1.63)、(81.14±1.24)、(78.31±0.76)μg/mL,明显低于其它变异链球菌组,与对照组相比也有显著性差异(P<0.05)。变异链球菌作用牙釉质的脱矿过程受到白色念珠菌分泌的Farnesol的调控,其脱矿作用受到明显的抑制。结论内源性Farnesol可抑制变异链球菌对牙釉质的脱矿作用。

Two farnesyl pyrophosphate synthases,GhFPS1–2,in Gossypium hirsutum are involved in the biosynthesis of farnesol to attract parasitoid wasps

Sesquiterpenoids play an import role in the direct or indirect defense of plants.Farnesyl pyrophosphate synthases(FPSs)catalyze the biosynthesis of farnesyl pyrophosphate,which is a key precursor of farnesol and(E)-β-farnesene.In the current study,two FPS genes in Gossypium hirsutum,GhFPS1 and GhFPS2,were heterologously cloned and functionally characterized in a greenhouse setting.The open reading frames for full-length GhFPS1 and GhFPS2 were each 1029 nucleotides,and encoded two proteins of 342 amino acids with molecular weights of 39.4 kDa.The deduced amino acid sequences of GhFPS1–2 showed high identity to FPSs of other plants.Quantitative real-time PCR analysis revealed that GhFPS1 and GhFPS2 were highly expressed in G.hirsutum leaves,and were upregulated in methyl jasmonate(MeJA)-,methyl salicylate(MeSA)-and aphid infestation-treated cotton plants.The recombinant proteins of either GhFPS1 or GhFPS2 plus calf intestinal alkaline phosphatase could convert geranyl diphosphate(GPP)or isopentenyl diphosphate(IPP)to one major product,farnesol.Moreover,in electrophysiological response and Y-tube olfactometer assays,farnesol showed obvious attractiveness to female Aphidius gifuensis,which is an important parasitic wasp of aphids.Our findings suggest that two GhFPSs are involved in farnesol biosynthesis and they play a crucial role in indirect defense of cotton against aphid infestation.

Farnesol纳米胶束的构建及对变形链球菌的抑菌作用研究

目的:构建水溶性Farnesol纳米胶束,并研究其对变形链球菌的抑菌作用。方法:采用乳化溶剂扩散法制备Farnesol纳米胶束。通过Malvern粒度仪检测粒径、聚合物分散性系数(PDI)、Zeta电位3项指标,计算载药量及包封率;并考察其稳定性、水溶性、体外释放行为等。通过扫描电镜评价Farnesol纳米胶束对变形链球菌菌斑生物膜形态的影响。采用微板法检测菌悬液中钙离子浓度,探讨Farnesol纳米胶束对变形链球菌产酸及釉质脱矿的抑制作用。结果:Farnesol纳米胶束水溶液澄清,无沉淀。粒径为(19.78±0.21)nm,Zeta电势为(-12.2±0.4)mV,PDI为0.089±0.040,载药量为(8.3±0.5)%,包封率为(46.89±1.10)%,12 h累计释放70%。该纳米胶束能够抑制变形链球菌抑制菌斑生物膜的形成,降低产酸能力抑制釉质脱矿,且呈浓度依赖性。结论:Farnesol纳米胶束制备良好,具有水溶性、稳定性和缓释性等特点,并可抑制变形链球菌的生长,降低其产酸能力,对龋病的防治有重要的临床指导价值。

Effects of Farnesol on Drug-Resistant and Non-Resistant <i>Candida albicans</i>: Implications for Cosmetic and Pharmaceutical Applications

Background: Farnesol is added to numerous consumer products that intentionally, or inadvertently come in contact with tissues that may harbor the opportunistic yeast, Candida albicans. Objective: This study explores biological consequences of the exposure of Candida albicans from community infections or from a panel of antifungal drug resistant organisms on growth and survival of these organisms when exposed to farnesol. Methods: ATCC supplied Candida albicans from the MP8 drug resistance panel and an additional 12 strains of community-acquired Candida albicans were cultured in the presence of farnesol. With standard micobiologic techniques and flow cytometry evaluation, a series of experiments considered growth, morphology, viability and entrance into the quiescent persister phenotype of Candida with emphasis on differences between drug resistant and community organisms. Results: Differences growth yield, relative cell size and heat susceptibility distinguished the community organisms from the drug-resistant organisms. Using a subset of these organisms, exposure to farnesol resulted in diminished growth, inhibited hyphal growth, diminished cell membrane integrity and increased heat stress susceptibility. Data provided suggest that exposure to farnesol pushes cultures of Candida albicans toward the quiescent persister phenotype. Conclusion: Exposure of drug resistant and community strains of Candida albicans are modestly affected by farnesol in ways that may lessen their pathogenic potential. In contrast, the tendency of farnesol to engender greater numbers of quiescent organisms could support persistence of Candida.

Influences of trans-trans farnesol,a membrane-targeting sesquiterpenoid,on Streptococcus mutans physiology and survival within mixed-species oral biofilms

Trans-trans farnesol (tt-farnesol) is a bioactive sesquiterpene alcohol commonly found in propolis (a beehive product) and citrus fruits, which disrupts the ability of Streptococcus mutans (S. mutans) to form virulent biofilms. In this study, we investigated whether tt-farnesol affects cell-membrane function, acid production and/or acid tolerance by planktonic cells and biofilms of S. mutans UA159. Furthermore, the influence of the agent on S. mutans gene expression and ability to form biofilms in the presence of other oral bacteria (Streptococcus oralis (S. oralis) 35037 and Actinomyces naeslundii (A. naeslundii) 12104) was also examined. In general, tt-farnesol (1 mmol·L-1) significantly increased the membrane proton permeability and reduced glycolytic activity of S. mutans in the planktonic state and in biofilms (P<0.05). Moreover, topical applications of 1 mmol·L-1 tt-farnesol twice daily (1 min exposure/treatment) reduced biomass accumulation and prevented ecological shifts towards S. mutans dominance within mixed-species biofilms after introduction of 1% sucrose. S. oralis (a non-cariogenic organism) became the major species after treatments with tt-farnesol, whereas vehicle-treated biofilms contained mostly S. mutans (>90% of total bacterial population). However, the agent did not affect significantly the expression of S. mutans genes involved in acidogenicity, acid tolerance or polysaccharide synthesis in the treated biofilms. Our data indicate that tt-farnesol may affect the competitiveness of S. mutans in a mixed-species environment by primarily disrupting the membrane function and physiology of this bacterium. This naturally occurring terpenoid could be a potentially useful adjunctive agent to the current anti-biofilm/anti-caries chemotherapeutic strategies.

Farnesol inhibits development of caries by augmenting oxygen sensitivity and suppressing virulence-associated gene expression in Streptococcus mutans

Streptococcus mutans is a primary etiological agent of dental caries.Farnesol,as a potential antimicrobial agent,inhibits the development of S.mutans biofilm.In this study,we hypothesized that farnesol inhibits caries development in vitro and interferes with biofilm fonnation by regulating virulence-associated gene expression.The inhibitory effects of farnesol to S.mutans biofilms on enamel surfaces were investigated by determining micro-hardness and calcium measurements.Additionally,the morphological changes of S.mutans biofilms were compared using field emission scanning electron microscopy and confocal laser scanning microscopy,and the vitality and oxygen sensitivity of S.mutans biofilms were compared using MTT assays.To investigate the molecular mechanisms of farnesol's effects,expressions of possible target genes luxS,brpA,ffh,recA,nth,and smx were analyzed using reverse-transcription polymerase chain reaction(PCR) and quantitative PCR.Farnesol-treated groups exhibited significantly higher micro-hardness on the enamel surface and lower calcium concentration of the supernatants as compared to the-untreated control.Microscopy revealed that a thinner film with less extracellular matrix formed in the farnesol-treated groups.As compared to the-untreated control,farnesol inhibited biofilm formation by 26.4%with500 μmol/L and by 37.1%with 1,000 μmol/L(P< 0.05).Last,decreased transcription levels of luxS,brpA,ffh,recA,nth,and smx genes were expressed in farnesol-treated biofilms.In vitro farnesol inhibits caries development and S.mutans biofilm formation.The regulation of luxS,brpA,ffh,recA,nth,and smx genes may contribute to the inhibitory effects of farnesol.

Tyrosol和Farnesol对白念珠菌生物被膜形成作用的基因表达谱研究

目的研究Tyrosol和Famesol对不同时相白念珠菌生物被膜形成的调控机制。方法研究对象为白念珠茵标准株SC5314。设立Tyrosol处理组、Farnesol处理组、Tyrosol和Famesol联合处理组、对照组。生物被膜6h和24h收集细胞，提取RNA，反转录cDNA。cDNA与白念珠菌全基因组8K表达谱芯片杂交。采用LuxSean双通道激光扫描仪进行扫描。LttxSean3．0图像分析软件对芯片图像进行分析。借助KEGG基因库对芯片数据进行生物信息学分析。结果不同生物被膜时相，Tyrosol和Famesol对白念珠菌基因表达调控作用不同。Tyrosol和Farnesol调控生物被膜形成相关基因、菌丝相基因和酵母相基因。Tyrosol是生物被膜基因表达的正向调控效应因子。Farnesol是负向调控效应因子。Tyrosol和Famesol主要调控的基因包括生物学过程、分子功能及细胞成分相关基因，这些基因主要通过参与物质代谢通路调控白念珠菌生物学特点及生物被膜形成。结论Tyrosol和Famesol通过调控白念珠菌哇物被膜形成相关基因调控毕物被膜形成。

Tyrosol和Farnesol对白念珠菌生物被膜形成作用初探

目的研究密度感应分子（quorum sensing molecule）tyrosol（对羟基苯乙醇）和farnesol（法呢醇）对白念珠菌生物被膜形成的调控作用。方法在tyrosol和farnesol干预下构建白念珠菌临床株和标准株生物被膜，在倒置显微镜下观察细胞形态，应用RT-PCR技术检测密度感应分子对白念珠菌HTA1和EFG1基因表达的调控作用，并采用MTT法观察密度感应分子对细胞活性的影响。结果tyrosol对白念珠菌生物被膜的菌丝发生和细胞活性无明显促进作用，也无法中和farnesol对菌丝发生和细胞活性的抑制作用。tyrosol使白念珠菌生物被膜内细胞HTA1的表达增强，对EFG1的表达并无明显影响；tyrosol不能改变farnesol对HTA1和EFG1表达的抑制作用。结论tyrosol能在一定程度恢复口腔白念珠菌生物被膜内细胞的活跃状态，但当tyrosol与farnesol同时存在时，tyrosol的作用被后者的抑制效应所掩盖，细胞对farnesol更敏感。

Systematic analysis of protein expression in Candida albicans exposed to farnesol

Background:The phenotypic switching of Candida spp.plays an important role in the development of vulvovaginal candidiasis(VVC).Farnesol,as a quorum-sensing molecule in Candida albicans,has the ability to prevent yeast-to-hyphal conversion in vitro.However,the mechanism underlying this ability is unclear.This study aimed to investigate changes in protein levels to better understand how farnesol impacts processes contributing to VVC.Methods:The isobaric tag for relative and absolute quantitation technique was used to detect protein expression in C.albicans strain SC5314(ATCC MYA-2876)with or without farnesol exposure.Proteins with a threshold fold change greater than 1.5 were screened and considered differentially expressed proteins.All the altered proteins were analyzed using Gene Ontology annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)annotation,and metabolic pathway annotation.Results:Between the farnesol-exposed group and the farnesol-unexposd group,we detected 297 altered proteins among all 2047 tested proteins based on a threshold fold change of more than 1.5(P<0.05).Eighty-seven of the 297 altered proteins exhibited metabolic enzyme activity and participated in 85 metabolic pathways according to KEGG pathway analysis.Most of these metabolic pathways were associated with central carbon metabolism processes.In the sterol synthesis pathway,which involves the synthesis of farnesol,ERG25(methylsterol monooxygenase)and ERG4(delta 24(24(1))-sterol reductase)were both down-regulated in the farnesol-exposed group.All six altered proteases associated with the oxidative phosphorylation process were down-regulated in the farnesol-exposed group relative to the farnesol-unexposed group.Conclusions:The mechanisms underlying farnesol-induced phenotype switching involves the adjustment of metabolic activities and epigenetic modification.Exogenous farnesol had an evident,but non-deterministic effect on the synthesis of ergosterol.The potential drug activity of farnesol warrants further investigation.

群体感应分子Farnesol联合CSA对白色念珠菌生物膜作用的实验研究

目的探讨群体感应分子法尼醇(Farnesol)联合钙调神经磷酸酶抑制剂环孢菌素A(CSA)对白色念珠菌的生物膜形成、形态转换、生长及活性、耐药性、凋亡反应和氧化应激反应的作用及其相关机制。方法体外构建生物膜状态白色念珠菌,分别经CSA、Farnesol、Farnesol联合CSA处理后,用qRT-PCR法检测生物膜状态白色念珠菌中生物膜形成过程中的相关基因CDR1、CEK1、CPH1、EFG1、ERG11、GPR1、HAT1、MDR1、HWP1、ALS3、TUP1mRNA表达水平的变化。结果白色念珠菌均具有不同程度的产膜能力,且单用CSA、Farnesol抗真菌药物对白色念珠菌生物膜的抑制率很低,而联合使用时,受试菌生物膜生长状态受到明显抑制。从临床血流感染中分离获得1株强产生物被膜白色念珠菌,命名为CA NX05;经不同药物组处理后生物膜状态白色念珠菌中的生物膜菌丝形成相关基因CEK1、CPH1、EFG1、ERG11、GPR1、HAT1、HWP1、ALS3、TUP1与其耐药性相关基因CDR1、MDR1的mRNA表达量与空白处理组相比均显著降低(F_(CEK1)=15.725,F_(CPH1)=6.230,F_(EFG1)=87.817,F_(ERG11)=17.527,F_(GPR1)=21.793,F_(HAT1)=65.318,F_(HWP1)=550.531,F_(ALS3)=10.514,F_(TUP1)=16.580,F_(CDR1)=8.089,F_(MDR1)=7.228;F>P,P<0.05)。结论群体感应分子Farnesol联合CSA处理较CSA及Farnesol处理能更有效地抑制白色念珠菌生物膜的形成,从而使其对抗真菌药物的敏感性增加,为临床合理使用抗真菌药物提供了科学导向。

超高效液相色谱-串联质谱法测定白念珠菌群体感应分子的含量

目的建立一种简便、可靠和灵敏的超高效液相色谱-串联质谱(UHPLC-MS/MS)方法,用于检测白念珠菌分泌的3种群体感应分子(法尼醇、酪醇、3-吲哚乙醇)的含量。方法样品经乙酸乙酯萃取后,采用Agilent 6470型三重四极杆串联质谱仪,通过正离子监测模式,以卡马西平为内标,在Agilent Poroshell 120 EC-C18色谱柱(3.0 mm×100 mm,2.7μm)上进行色谱分离。采用梯度洗脱,流动相为0.1%甲酸水溶液(A)和乙腈(B),洗脱梯度为0~3 min 20%~40%B、3~4 min 40%~80%B、4~8 min 80%B,流速为0.5 mL/min,进样量为5μL,柱温为25℃,分析时间为8 min,平衡时间为2 min。采用电喷雾离子源、正离子多反应监测模式进行质谱分析。结果法尼醇、酪醇、3-吲哚乙醇的专属性和线性关系良好(r均>0.999),精密度和准确度均良好(日内、日间精密度均<5%,准确度的绝对值均<10%),平均回收率为90%~115%;3种条件(室温放置4 h、4℃自动进样器放置24 h及冻融3次)下的稳定性均符合方法学要求。在浮游型样品中,3种群体感应分子的含量均随培养时间的延长而增加;而在被膜型样品中,法尼醇和酪醇在被膜成熟阶段含量降低。结论该UHPLC-MS/MS方法可用于测定白念珠菌分泌的法尼醇、酪醇、3-吲哚乙醇的含量,为真菌群体感应分子的快速、准确检测提供参考。

法尼醇对白念珠菌生物膜葡聚糖的影响及白念珠菌耐药相关性

目的探索法尼醇对白念珠菌生物膜细胞壁葡聚糖的影响及白念珠菌的耐药相关性。方法采用浓度梯度递增法诱导构建白念珠菌耐药株,KONT真菌显色MIC药敏系统鉴定耐药株模型。本实验分为对照组、法尼醇处理组和耐药株组。利用透射电镜观察各组生物膜细胞壁,通过qPCR比较分析各组葡聚糖相关基因PIR1、PHR2、BGL2和GSC1的表达。结果本实验白念珠菌耐药株模型构建成功。透射电镜观察发现,法尼醇处理后各时相白念珠菌生物膜细胞壁出现形态改变。24 h生物膜中,对照组白念珠菌生物膜细胞壁的厚度为(220.10±2.25)nm;法尼醇处理组白念珠菌细胞壁电子颗粒减少,细胞壁厚度变薄为(145.90±4.05)nm;而耐药株组白念珠菌细胞壁电子颗粒增多,细胞壁厚度增加到(299.47±3.33)nm。qPCR结果显示,与对照组相比,法尼醇处理组PIR1和PHR2表达上调(P<0.05),GSC1表达下调(P<0.05);耐药株组PHR2表达下调(P<0.05),GSC1表达上调(P<0.01)。结论法尼醇可能通过调控葡聚糖相关基因PHR2、PIR1和GSC1影响白念珠菌细胞壁的形态和结构,而细胞壁的形态和结构与白念珠菌耐药性相关。

核苷(酸)类似物联合聚乙二醇干扰素对慢性乙型肝炎大鼠法尼醇X受体-成纤维细胞生长因子19通路、枯否细胞极化的影响

目的 :探究核苷(酸)类似物联合聚乙二醇干扰素对慢性乙型肝炎大鼠法尼醇X受体(FXR)-成纤维细胞生长因子19(FGF19)通路、枯否细胞极化的影响。方法 :选取SPF级SD雄性大鼠,随机分为正常组、模型组、核苷(酸)类似物(核苷酸)组、聚乙二醇干扰素(干扰素)组、联合组。除正常组外,均采用腹腔注射乙型肝炎病毒进行慢性乙型肝炎建模。建模成功后,对核苷酸组灌胃10 mg/kg拉米夫定,对干扰素组皮下注射5μg/kg聚乙二醇干扰素,对联合组给予拉米夫定联合聚乙二醇干扰素治疗,正常组、模型组同期灌胃同体积生理盐水。酶联免疫吸附法检测血清病毒,全自动生化分析仪检测肝功能,H-E染色法检测肝组织病理形态,免疫印迹法检测FXRFGF19通路蛋白表达,免疫组织化学法检测枯否细胞极化。结果 :与正常组相比,模型组血清乙型肝炎表面抗原(HBsAg)、乙型肝炎E抗原(HBeAg)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)含量、iNOS、CD163阳性表达率显著升高,肝组织FXR、FGF19蛋白表达显著降低。与模型组相比,核苷酸组、干扰素组、联合组血清HBsAg、HBeAg、ALT、AST、TBIL含量、iNOS、CD163阳性表达率显著降低。肝组织FXR、FGF19蛋白表达显著升高,联合组比干扰素组降低显著。结论 :核苷(酸)类似物联合聚乙二醇干扰素,可显著激活FXR-FGF19通路,并抑制枯否细胞M1极化,促进枯否细胞M2极化,对慢性乙型肝炎大鼠具有改善作用。

血清胆汁酸水平与2型糖尿病的相关性研究

2型糖尿病(type 2 diabetes mellitus, T2DM)作为一种代谢性疾病,已经成为继肿瘤、心血管病变之后第三大严重威胁人类健康的慢性疾病。糖尿病临床表型中以T2DM为主。T2DM发病机制相对复杂,目前认为胰岛β细胞功能缺陷、胰岛素抵抗是2型糖尿病发生的主要原因。同时糖尿病患者更易引起血脂、脂蛋白异常,增加各种糖尿病并发症的风险。有研究表明糖尿病患者常伴有总胆汁酸池的增加和胆汁酸成分的改变。胆汁酸除了在膳食脂肪的吸收和胆固醇的稳态中发挥作用,还参与许多信号通路的调控。此外,胆汁酸还通过调节自身的肝肠循环,维持三酰甘油、胆固醇的平衡,并参与能量和血糖水平的调控。本文主要针对血清胆汁酸与2型糖尿病的关系及其研究进展进行综述。

胆汁酸及其受体在非酒精性脂肪性肝病发病机制中的作用及药物治疗的研究进展

非酒精性脂肪性肝病(NAFLD)是以肝细胞内脂质蓄积为主要特征的肝脏代谢紊乱疾病,已成为全球范围内慢性肝病的主要病因。20%~30%的NAFLD会进展为非酒精性脂肪性肝炎(NASH),NASH的发展与多种代谢紊乱密切相关。胆汁酸及其受体功能在NASH的发病机制中起着重要作用,胆汁酸受体是治疗NASH重要的靶点。本文对胆汁酸及其受体在NAFLD和NASH发展中的作用,特别是关于法尼醇X受体(FXR)在不同组织(包括肝脏和肠道)中的功能的研究予以综述,介绍基于胆汁酸及其受体的NASH治疗药物的研究进展。