Cholic acid mitigates osteoarthritis by inhibiting the NF-κB/PERK/ SIRT1 signaling pathway

Introduction:Cholic acid(CA)is a natural steroid useful in treating chronic bronchitis and cholecystitis.On the other hand,its potential impact on osteoarthritis(OA)is unknown.Objective:Using an in vitro and in vivo osteoarthritis model,we sought to assess the chondroprotective properties of CA.Methods:We employed the Cell Counting Kit-8 to measure the impact of CA on chondrocyte activity to assess the toxicity of the cells.Multiple molecular biology experimental techniques were used to investigate potential signaling pathways that CA may use to prevent inflammation and give chondrocytes protection.Furthermore,how CA affects the OA model in Sprague-Dawley(SD)rats was evaluated.Results:CA significantly suppressed the up-regulation of the interleukin-1β(IL-1β),cyclooxygenase-2(COX-2),and matrix metalloproteinase 13(MMP-13)and the downregulation of aggrecan and type II collagen A1(COL2A)in chondrocytes treated tumor necrosis factor-alpha(TNF-α).Differentially expressed genes(DEG)enrichment revealed IL-17,TNF,chemokine,cytokine-cytokine receptor,toll-like receptor,and nucleotide oligomerization domain-like receptor were the primary signaling pathways.The enriched DEGs included CXCL6,CCL20,MMP3,CXCL3,CXCL11,CCL5,CXCL10,MMP9,MMP13,and CXCL2;these DEGs are involved in inflammatory responses and their expression induced by TNF-αwas reversed by CA treatment.CA inhibits p65 nuclear translocation and inhibitory subunit kappa B alpha(IκBα)phosphorylation induced by TNF-α.Furthermore,CA attenuated protein expression of protein kinase RNA-like endoplasmic reticulum kinase(PERK),inositol-requiring transmembrane kinase/endoribonuclease 1α(IRE1α),glucose regulatory protein 78(GRP78),and sirtuin 1(SIRT1),and down-regulation of phosphorylation of AMP-activated protein kinase-α(p-AMPKα)in TNF-α-treated chondrocytes.Conclusions:CA significantly ameliorated cartilage degradation in the OA rat model.CA alleviated the inflammatory response through the nuclear factor kappa B/PERK/SIRT1 axis and ameliorated cartilage degradation.

Study on the mechanism of cholic acid derivatives in traditional Chinese medicine based on the regulation of gene expression

Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles of Michigan Cancer Foundation-7(MCF-7)cells treated with or without 4 cholic acid derivatives were detected by gene chip technology.Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map(CMap)database.The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking.The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database,and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231(MDA-MB-231)cells.Results:Compared with the reference genome in the CMap database,the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic,anticancer,anti-inflammatory,and antiinfective drugs.Among them,4 derivatives were associated with antianxiety drugs,and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gammaaminobutyric acid(GABA)receptors.Moreover,the cytoskeletal pathway is one of the pathways enriched in the derivatives.Of them,ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells.Conclusion:The gene expression detection method,combined with CMap and pathway enrichment analysis,could be used to study the mechanism of the active ingredients of TCM.In addition,our research showed that cholic acid derivatives have a potential affinity for membrane receptors,where they can exert anxiolytic activity by modulating opioid receptor,GABA receptor,and dopamine receptor.Moreover,ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation,probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.

Effect of Cholic Acid on Fetal Cardiac Myocytes in Intrahepatic Choliestasis of Pregnancy

This study examined the effect of cholic acid （CA） on cultured cardiac myoeytes （CMs） from neonatal rats with an attempt to explore the possible mechanism of sudden fetal death in intra- hepatic cholestasis of pregnancy （ICP）. Inverted microscopy was performed to detect the impact of CA on the beating rates of rat CMs. MTT method was used to study the effect of CA on the viability of CMs. CMs cultured in vitro were incubated with 10 ~maol/L Ca2＋-sensitive fluorescence indicator fluo-3/AM. The fluorescence signals of free calcium induced by CA were measured under a laser scanning confocal microscope. The results showed that CA decreased the beating rates of the CMs in a dose-dependent manner. CA could suppress the activities of CMs in a time- and dose-dependent manner. CA increased the concentration of intracellular free calcium in a dose-dependent manner. Our study suggested that CA could inhibit the activity of CMs by causing calcium overload, thereby leading to the sudden fetal death in ICP.

Study on synthesis and distribution in vivo of 5-Fu-cholic acid conjugate

A series of hepatic targeting drugs, 5-Fu-cholic acid conjugate T1-T5, were synthesized. 5-Fu and cholic acid was selected as starting material, after N-hydroxymethylation, condensation, hydrogenolysis to obtain carboxylated 5-Fu 5a-e. Carboxylated 5-Fu 5a-e were condensated with intermediate 3-hydroxyethyl cholic acid benzyl ester 6 to get 7a-e, 7a-e were deprotected to get T1- T5.

Fine Structure of Hydrogen Bonds in Cholic Acid Revealed by 2DIR Spectroscopy

Based on cryogenic FT-IR spectroscopic studies of hydrogen bonds in cholic acid, two-dimensional FT-IR spectroscopy was applied to enhance our understanding of the hydrogen bonds of cholic acid. Fine spectral structures were revealed by asynchronous 2D FT-IR spectra. The co-relationship among various bands was discussed according to the synchronous 2D FT-IR spectrum.

SWELLING AND WETTABILITY OF LIGHT-CURED METHACRYLATE-BASED DENTAL RESINS PREPARED FROM CHOLIC ACID

2＇-methacryloxy-3α, 7α, I2α- trimethacryloyl cholic acid ethyl ester （CAGE4MA） has been prepared from cholic acid. Photo-polymeric resins were prepared from CAGE4MA. 2,2-bis[4-（2-hydroxy-3-methacrylyloxypropoxy）phenyllpropane （bis-GMA） was used for comparison, triethyleneglycol dimethacrylate （TEGDMA） was used as diluent. The polymerization was initiated by camphoroquinone （CQ）/N, N-dimethylaminoethyl methacrylate （DMAEMA） system. The conversion of CAGE4MA was 39% when the reaction time is 60s, which is lower than bis-GMA and TEGDMA. The swelling value of CAGE4MA resin was 0.41% in distilled water, which is much lower than those of bis-GMA resin （2.04%） and TEGDMA resin （4.77%） under the same conditions. Copolymers from CAGE4MA and TEGDMA have been prepared. With the increase of TEGDMA in mixture, the degree of conversion of CA GE4MA and swelling value increased. The swelling values of photocured resins in 0.1mol/L HCl were also measured.

SYNTHESIS AND THERMAL PROPERTIES OF A NEW CHOLIC ACIDCONTAINING COPOLYMER

A new copolymer was synthesized by free radical polymerization in solution from methyl 3α-methylacryloyl-7α, 12α-dihydroxy-5β-cholan-24-oate (MACAME) and maleic anhydride (MAN). The copolymer was characterized by FT-IR and functional group analysis. The reactivity ratios of the two monomers were estimated [r_1 = 11.6 (MACAME), r_2 = 0.01(MAN)] by conducting a series of copolymerizations with a variety of monomer feed compositions and analyzing thecopolymer composition. Thermogravimetric and differential scanning calorimetric analyses of the samples indicate that thecopolymer possesses good thermal stability. The temperature at which the copolymer samples experienced a 10% weight loss(T_(WL)) is over 287℃, and the T_g ranged from 174 to 185℃ for the copolymers.

The Synthesis and Anion Binding of Novel Cholic Acid-based Molecular Clefts Containing Unsymmetrically Disubstituted Urea Unit

A novel type of chiral molecular clefts consisting of a rigid deoxycholic acid methyl ester backbone and chiral unsymmetrically disubstituted urea side chain have been designed and synthesized. All these new receptors 3a^c and the corresponding key intermediates 1a^c and 2a^c are new compounds, their structures were confirmed by 1HNMR, IR, MS spectra and elemental analysis. These molecular clefts showed binding ability for halide anions.

Isotopic Shifts of the infrared Spectra of Cholic Acid and Sodium Cholate

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The Binding of Cholic Acid by Hemicellulose and Pectin of Yard-Long Bean [Vigna sesquipedalis （L.） Fruhw]

The aim of the study was to describe the binding of cholic acid by hemicellulose and pectin of yard-long bean at gastrointestinal system （in vitro）, through variation of acidity （pH 3, 5 and 7） and boiling time （raw/0, 5, 20 and 35 minutes） of yard-long bean. Two-way Anova （α= 5%） and functional groups analysis by infrared spectrophotometer were applied for the binding description. The results of the study showed： （1） The highest binding percentage of cholic acid by dietary fiber of yard-long bean at pH 3-raw treatment （76.603%）; （2） Cholic acid binding via C = O/ester or acid of hemicellulose, C-O-C/cyclic ether of pectin, while C = O/ester or acid of oectin through iron.

HPLC-MS/MS法同时测定清开灵口服液中7种成分的含量

目的 建立高效液相色谱-质谱联用(HPLC-MS/MS)法同时测定清开灵口服液中7种成分含量。方法 采用Waters ACQUITY UPLC BEH C_(18)色谱柱(2.1 mm×10 mm,1.7μm);以含10 mmol·L^(-1)乙酸铵和0.1%甲酸的水溶液(A)及甲醇(B)为流动相,梯度洗脱;电喷雾离子源,正、负离子多反应监测(MRM)模式进行定量分析。结果 腺苷、绿原酸、咖啡酸、栀子苷、黄芩苷、猪去氧胆酸和胆酸质量浓度分别在0.100 4~3.213、0.784 5~8.982、0.998~3.194、0.622 5~19.92、25.05~300.6、2.513~30.15和7.775~93.30μg·m L^(-1)范围内与峰面积呈良好线性关系(r≥0.999 0);平均回收率(n=6)分别为100.9%、98.74%、101.2%、100.2%、100.8%、99.97%和98.94%,RSD分别为1.58%、0.59%、1.78%、1.25%、0.65%、1.69%和1.07%。15批样品中腺苷、绿原酸、咖啡酸、栀子苷、黄芩苷、猪去氧胆酸和胆酸的含量范围分别为0.12~0.18、0.19~0.24、0.06~0.09、0.34~0.37、4.54~4.85、0.49~0.67和1.82~2.19 mg·m L^(-1)。15批样品测定结果较为接近。结论 该方法具有良好的灵敏度、准确性和重复性,可为清开灵口服液的质量控制和后续研究提供参考及数据支持。

胆酸和去氧胆酸抗惊厥作用的血清代谢组学研究

目的:探究胆汁酸单体化合物胆酸(cholic acid,CA)和去氧胆酸(deoxycholic acid,DCA)的抗惊厥作用机制。方法:将3周龄雄性SD大鼠随机分为对照组、模型组、丙戊酸钠组(sodium valproate/valproic acid,VPA,189 mg/kg)、CA组(60 mg/kg)和DCA组(60 mg/kg),每组9只,对照组及模型组为假给药,各给药组于造模前1 h预给药,连续给药16 d。采用(45.0±0.5)℃水浴建立惊厥大鼠模型,每隔1 d水浴1次,共计8次,观察记录模型组及各给药组大鼠惊厥发作时间、惊厥结束时间,对大鼠惊厥发作行为的严重程度进行评分。检测大鼠血清及海马组织中白介素1β(interleukin 1β,IL-1β)、肿瘤坏死因子α(tumor necrosis factor α,TNF-α)和IL-6含量及海马组织中谷氨酸(glutamic acid,Glu)和γ-氨基丁酸(γ-aminobutyric acid,GABA)含量,苏木精-伊红(hematoxylin-eosin,HE)染色观察海马神经元病理损伤。超高效液相色谱仪串联高分辨质谱技术对大鼠血清进行代谢组学分析。结果:与模型组相比,各给药组大鼠惊厥潜伏期均显著延长,惊厥持续时间显著缩短(P均<0.001);VPA组和DCA组惊厥发作等级显著降低(P <0.001,P <0.01),CA组差异无统计学意义。与对照组相比,模型组血清和海马组织中TNF-α,IL-6和IL-1β含量均显著升高(P <0.001),海马组织中Glu和GABA含量均显著升高(P <0.001);与模型组相比,DCA组和VPA组各项生化指标水平均显著降低(P <0.001),而与模型组相比,除血清中IL-1β和海马组织IL-6的水平外,CA组其他各项指标均显著降低(P <0.01)。海马组织HE染色结果显示,与对照组相比,模型组大鼠海马组织中锥体细胞胞体紧缩,体积变小,染色加深,嗜碱性增强,胞质胞核分界不清;与模型组相比,各给药组大鼠海马神经元细胞形态得到明显改善。其中,DCA组大鼠海马神经元细胞形态与VPA组相近。血清代谢组学分析结果经过数据处理、文献及数据库比对,共鉴定出312个差异化合物。通过主成分分析(principal component analysis,PCA)及正交偏最小二乘法判别分析,共筛选出9个差异化合物;代谢通路富集结果显示,CA和DCA的抗惊厥作用主要涉及柠檬酸循环、氨基酸代谢和丁酸代谢通路。结论:CA和DCA对热性惊厥大鼠的行为学和生化指标等均具有一定的改善作用,其作用机制可能与惊厥过程中的能量代谢、氨基酸代谢和丁酸等短链脂肪酸代谢有关。

A Simple and Novel Electrochemical Sensor Based on Phosphomolybdic-Polypyrrole Film Modified Electrode for Highly Sensitive Detection of Cholic Acid

A simpe electrochemical sensor for detection of cholic acid （CA） was designed by modifying phosphomolybdate （PMol2） doped polypyrrole （PPy） film on glassy carbon electrode （PMo12-PPy/GCE）. The electrochemical behavior of CA on PMo12-PPy/GCE was investigated by cyclic voltammetry and 0.5 order differential voltammetry. The results indicated that CA had high inhibitory activity toward the peak currents of PMo12-PPy/GCE. The reduction peak currents were linearly related to the logarithmic value of the concentration of CA from 1.0 × 10^- 7 to 1.0 × 10^-3 mol/L with a low detection limit of 1.0 × 10^- 8 mol/L. The developed sensor exhibited excellent sensitivity, selectivity and stability for detection of CA, and it could be successfully applied to detect the level of CA in the urine samples. Moreover, the response mechanism of CA on the PMo12-PPy/GCE was discussed in detail.

糖皮质激素联合腺苷蛋氨酸、熊去氧胆酸治疗药物性急性重度胆汁淤积性肝病的临床疗效

目的探讨糖皮质激素联合腺苷蛋氨酸(S-adenosyl-L-methionine,SAMe)、熊去氧胆酸(Ursodeoxycholic acid,UDCA)治疗药物性急性重度胆汁淤积性肝病(Drug-induced cholestatic liver disease,DICLD)的效果。方法选取2018年1月至2022年12月青海省第四人民医院收治的106例急性重度DICLD患者,采用随机数字表法将其分为两组,各53例。对照组给予SAMe、UDCA治疗,观察组给予SAMe、UDCA联合糖皮质激素(甲泼尼龙)治疗。治疗2周后检测并比较两组患者肝功能指标[碱性磷酸酶(Alkaline phosphatase,ALP)、总胆汁酸(Total bile acid,TBA)、γ-谷氨酰转移酶(γ-glutamyltransferase,γ-GT)及血清胆红素(Total bilirubin,TBil)]、生化指标[前白蛋白(Prealbumin,PA)、白蛋白(Albumin,ALB)]及免疫功能指标[可溶性黏附分子1(Soluble vascular cell adhesion molecule-1,sVCAM-1)、干扰素γ(Interferon-γ,IFN-γ)]水平并评估两组患者临床疗效。采用Spearman相关性建议分析临床疗效与生化、免疫功能指标的相关性,并观察两组治疗方案的安全性。结果观察组治疗总有效率为90.57%,高于对照组的73.58%(P<0.05)。治疗后,两组ALP、TBA、γ-GT、TBil、PA、ALB、sVCAM-1、IFN-γ水平均较治疗前降低(P<0.05),且观察组ALP、TBA、γ-GT、TBil、PA、ALB、sVCAM-1、IFN-γ水平均低于对照组(P<0.05)。Spearman相关性分析显示,患者临床疗效与PA、ALB水平呈正相关,与sVCAM-1、IFN-γ水平呈负相关(P均<0.05)。观察组、对照组药物不良反应率分别为18.87%、11.32%,两组比较差异无统计学意义(P>0.05)。结论糖皮质激素联合SAMe、UDCA能够提高急性重度DICLD患者疗效,改善肝功能及炎症因子水平,提高机体免疫功能,且安全性良好。

New steroid dimer derived from cholic acid as receptor for lanthanum(Ⅲ) and calcium(Ⅱ) nitrates

New steroid dimer,ethylene bridged bis-carbamate(3) was synthesized from cholic acid in few steps. Complexes of 3 with lanthanum(Ⅲ) and calcium(Ⅱ) nitrates were prepared in reaction of 3 and appropriate metal salts. They were characterized by spectral data(Infrared(IR) ,ultraviolet-visible(UV/Vis) ,nuclear magnetic resonance(NMR) spectroscopy and fast-atom bombardment(FAB) ,electrospray(ESI) and matrix-assisted laser desorption/ionization mass spectrometry(MALDI-MS)) and elemental analysis. The similarity in complexing behavior of steroidal dimer toward calcium and lanthanum ions was observed.

胆酸对急性酒精肝损伤小鼠的保护作用及机制研究

目的 研究胆酸对急性酒精肝损伤的保护作用,并从代谢组学的角度探讨胆酸干预急性酒精肝损伤小鼠的潜在生物标志物和其保护机制。方法 采用56%酒精灌胃造急性酒精肝损伤小鼠模型,通过组织病理学染色和各项生化指标检测胆酸的保护作用。采用液相色谱-质谱联用技术(LC-MS)检测各组小鼠血清代谢物,使用SIMCA-P14.1、SPSS、Metabo Analyst等进行数据分析,研究各组间的差异代谢物和胆酸的作用机制。结果 胆酸组的谷丙转氨酶(ALT)、谷草转氨酶(AST)、丙二醛(MDA)、白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)指标低于模型组,差异有统计学意义(P<0.05),且胆酸组的谷胱甘肽(GSH)、超氧化物歧化酶(SOD)指标高于模型组,差异有统计学意义(P<0.05)。通过血清代谢组分析,在模型组与正常组中鉴定出31个差异代谢物,并发现其富集于苯丙氨酸代谢、嘌呤代谢、萜类骨架生物合成和不饱和脂肪酸生物合成途径。在胆酸组与模型组中鉴定出34个差异代谢物,并发现其富集于苯丙氨酸代谢和嘌呤代谢途径。结论 胆酸能够显著缓解小鼠因大量摄入酒精而导致的肝脏氧化应激和炎症反应,通过对比各组间的差异代谢物和差异代谢通路,发现胆酸能够调节嘌呤代谢和苯丙氨酸代谢异常,表明胆酸对急性酒精肝损伤有一定的保护作用,其机制可能与改善嘌呤代谢和苯丙氨酸代谢有关。

妊娠期肝内胆汁淤积症孕妇血清总胆酸水平和胎儿心脏功能的相关性

目的探讨妊娠期肝内胆汁淤积症孕妇血清总胆酸水平和胎儿心脏功能的相关性。方法选择2021年1月至2022年12月在睢县妇幼保健院妇产科接诊的130例妊娠期肝内胆汁淤积症孕产妇(观察组)及同时间段在该医院妇产科实施检查的130例健康孕产妇(对照组)的数据资料实施回顾性分析。比较两组孕产妇的血清总胆酸、丙氨酸基转氨酶、γ-谷氨酰转肽酶水平。比较两组孕产妇的围产儿不良结局情况(早产、羊水粪染、宫内窘迫)。比较两组新生儿的脐带血心肌肌钙蛋白Ⅰ(cTnⅠ)、胎儿左心室Tei指数。分析孕产妇血清总胆酸和新生儿的脐带血cTnⅠ、胎儿左心室Tei指数的相关性。结果观察组孕产妇的血清总胆酸、丙氨酸基转氨酶、γ-谷氨酰转肽酶水平均显著高于对照组,差异有统计学意义(P<0.05)。观察组孕产妇的围产儿不良结局发生率均高于对照组,差异有统计学意义(P<0.05)。观察组新生儿的脐带血cTnⅠ、胎儿左心室Tei指数均显著高于对照组,差异有统计学意义(P<0.05)。孕产妇血清总胆酸和新生儿的脐带血cTnⅠ、胎儿左心室Tei指数均呈正相关,差异有统计学意义(r=0.683,0.573,P<0.05)。结论妊娠期肝内胆汁淤积症孕妇的血清总胆酸水平明显增高,血清总胆酸水平同胎儿心脏功能之间也具有密切的相关性。增高的胆酸会对胎儿心肌构成损伤,因此需要对孕妇给予重点关注。

不同厂家八宝惊风散中人工牛黄胆汁酸类活性成分的含量测定及差异分析

目的建立同时测定八宝惊风散中人工牛黄有效成分(胆酸、猪去氧胆酸和牛磺胆酸钠)含量的方法,比较不同厂家样品中3个成分的含量差异。方法采用超高效液相串联质谱法测定3个厂家9批八宝惊风散中胆酸、猪去氧胆酸和牛磺胆酸钠的含量,色谱柱为Phenomenex Luna®C18,流动相为乙腈-水(梯度洗脱),流速为0.5 mL/min,柱温为40℃,进样量为2μL。质谱采用负离子单四极杆模式,胆酸、猪去氧胆酸和牛磺胆酸钠的m/z分别为407.2、392.2、514.2。以3个成分的含量为指标,对9批样品进行聚类分析和主成分分析。结果胆酸、猪去氧胆酸和牛磺胆酸钠的线性范围分别为5.48~548.40、5.38~538.40、4.74~474.05 ng/mL(r≥0.9993);精密度、重复性、稳定性(24 h)的RSD均不高于3.7%(n=6),平均回收率分别为103.3%、103.3%、101.6%,RSD分别为3.3%、3.4%、4.2%(n=6)。9批样品中胆酸、猪去氧胆酸、牛磺胆酸钠的含量分别为0.702~1.711、0.599~2.049、0.664~1.752 mg/g。A厂家样品中3个成分的平均含量较高,批间差异最小;C厂家样品中3个成分的平均含量最低,批间差异较大。聚类分析基本可以区分不同厂家的样品;以主成分综合得分为指标进行聚类分析,结果与含量聚类分析结果基本一致。结论成功建立了同时测定八宝惊风散中人工牛黄3个胆汁酸类有效成分含量的方法。各厂家样品中3个成分的含量存在较大差异。

UPLC-MS/MS检测鸡蛋中胆酸及其衍生物

目的:建立式固相萃取结合超高效液相色谱—串联质谱法(UPLC-MS/MS)检测鸡蛋中胆酸、去氧胆酸和去氢胆酸的方法。方法:样品经甲醇提取,PRiME HLB净化后,经C18色谱柱(100 mm×2.1 mm, 3.0μm)分离,甲醇—0.1%氨水溶液(体积分数)为流动相,梯度洗脱,负离子扫描和选择反应监测模式(SRM)检测,外标法定量。结果:胆酸(CA)、去氧胆酸(DCA)、去氢胆酸(DHCA)在0.5~500.0 ng/mL质量浓度范围内呈良好的线性关系,相关系数>0.999。CA、DCA和DHCA的检出限为1.0μg/kg,定量限为3.3μg/kg。在加标水平为1~10μg/kg, CA、DCA和DHCA加标回收率为93.7%~102.5%,RSD为1.8%~9.2%。对随机抽取的30批次鸡蛋进行检测,28批次样品检出胆酸。结论:该方法快速,灵敏度和准确度高,可作为鸡蛋中胆酸类药物及其衍生物的检测方法。

邻苯二甲酸酯对胆汁淤积性肝病影响的研究进展

胆汁淤积性肝病是由于胆汁生成、排泄及代谢障碍,造成胆汁在肝脏沉积所致的一类常见肝胆疾病。目前胆汁淤积性肝病的致病因素尚未充分阐明,但有研究者认为环境因素可能在其中发挥重要作用。环境污染物邻苯二甲酸酯已被证实可干扰人类内分泌系统,对人体具有潜在毒性,危及肝肾功能,且可能增加肝内胆汁淤积的发生风险。基于此,本研究对邻苯二甲酸酯与胆汁淤积性肝病的关系进行综述,分别从临床研究、动物实验研究和体外实验研究及潜在机制进行总结,为胆汁淤积性肝病的预防以及临床治疗提供思路和参考。