Polymorphism of Human Organic Cationic Transporter1 (C480G) in Egyptian Chronic Myeloid Leukemia Patients on Imatinib

Background: Human organic cationic transporter1 (Hoct1) is a plasma membrane transporter responsible for the main influx of Imatinib into chronic myeloid leukemia (CML) cells. Single nucleotide polymorphisms (SNPs) in the gene coding for hOCT1 are important factors causing Imatinib resistance. We investigated the frequency of hOCT1 SNP C480G among Egyptian CML patients and its relation to early molecular response as an indicator of treatment outcome. Materials and Methods: Two groups of CML patients were included in this study. Group I consisted of 25 patients responding to Imatinib treatment (Imatinib responsive) and group II consisted of 25 patients resistant to Imatinib (Imatinib resistant). Response criteria were assessed according to the NCCN (National Comprehensive Cancer Network) guidelines 2017. Twenty healthy controls of matched age and sex were also included (group III). For all patients, we studied hOCT1 C480G at initial presentation using Taqman drug metabolism genotyping as well as BCR-ABL percent at diagnosis and after 3 months interval. Results: hOCT1 C480G was present in 32% of studied CML patients. CC (wild) was detected in 68% of group I and 64% of group II. CG (mutant heterozygous) was present in 28% of group I and 36% of group II while GG (mutant homozygous) was detected in only one case in group I. CG was also detected in 15% of control subjects There was no significant difference between hOCT1 C480G polymorphism and Early Molecular Response (χ2 = 0.089, p = 0.765). Conclusions: hOCT1 C480G polymorphism has no association with Imatinib resistance in Egyptian population. However, further studies on a larger number of patients are still needed to confirm this finding.

Influence of organic anion transporting potypeptide(SLCO1B1 and SLCO1B3)genetic polymorphisms on mycophenolic acid in Chinese kidney transplantation patients

Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations ( SLCO1B3 T334G,SLCO1B1 A338G) were detected in 68 recipi-

Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis

Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.

Isolation and Identification of Phosphate-accumulating Strain PAO3-1 and Its Phosphorus Removal Characteristics

A phosphate-accumulating bacteria strain PAO3-1 was isolated from biological phosphorus removal sludge supplied with sodium acetate as carbon source under stable performance. This strain has good enhanced biological phosphorus removal effect on normal activated sludge system. Phosphorus removal ratio was raised form 44% with no added strain to more than 82% with strain strengthening biological phosphorus removal. It is identified to be Alcaligenes sp. according to its morphology, biochemical characteristics and 16S rDNA sequence analysis. The cell of strain PAO3-1 is straight bacilli form, 0.4×1.1μm, no flagellum, gram negative and special aerobiotic. The optimal temperature and pH for growth are 32℃-37℃ and 5.5-9.5, respectively. The shape of slant clone is feathery. The phosphate accumulating rate of strain PAO3-1 was 8.1mgP/g cell·h, and 14.3 mgP/g cell·h when in phosphate-starving situation, which was 76.5% higher than that in non-starving situation. Its phosphate release rate of log course in anaerobic phase and in culture without phosphorus was 7.6mgP/g cell·h, while in stable course the rate was 6.1mgP/g cell·h. The rate in stable course was 19.7% lower than that in log course.

Nondoped-type White Organic Light-Emitting Diode Using Star-Shaped Hexafluorenylbenzene as an Energy Transfer Layer

White organic light-emitting diodes （WOLEDs） with a structure of indium-tin-oxide （ITO）/N,N＇-bis- （1-naphthyl）-N,N＇-diphenyl- （1, 1＇-biphenyl）-4,4＇-diamine （NPB）/1,2,3,4,5,6-hexakis（9,9-diethyl-9H-fluoren-2- yl）benzene （HKEthFLYPh）/5,6,11,12-tetraphenylnaphtacene （rubrene）/tris（8-hydroxyquinoline） aluminum （Alq3）/Mg：Ag were fabricated by vacuum deposition method, in which a novel star-shaped hexafluorenyl- benzene HKEthFLYPh was used as an energy transfer layer, and an ultrathin layer of rubrene was inserted between HKEthFLYPh and Alq3 layers as a yellow light-emitting layer instead of using a time-consuming doping process. A fairly pure WOLED with Commissions Internationale De L＇Eclairage （CIE） coordinates of （0.32, 0.33） was obtained when the thickness of rubrene was 0.3 nm, and the spectrum was insensitive to the applied voltage. The device yielded a maximum luminance of 4816 cd/m2 at 18 V.

Intestinal OCTN2-and MCT1-targeted drug delivery to improve oral bioavailability

Various drug transporters are widely expressed throughout the intestine and play important roles in absorbing nutrients and drugs,thus providing high quality targets for the design of prodrugs or nanoparticles to facilitate oral drug delivery.In particular,intestinal carnitine/organic cation transporter 2(OCTN2)and mono-carboxylate transporter protein 1(MCT1)possess high transport capacities and complementary distributions.Therefore,we outline recent developments in transporter-targeted oral drug delivery with regard to the OCTN2 and MCT1 proteins in this review.First,basic information of the two transporters is reviewed,including their topological structures,characteristics and functions,expression and key features of their substrates.Furthermore,progress in transporter-targeting prodrugs and nanoparticles to increase oral drug delivery is discussed,including improvements in the oral absorption of anti-inflammatory drugs,antiepileptic drugs and anticancer drugs.Finally,the potential of a dual transporter-targeting strategy is discussed.

A NEW POLYMER-BOUND 1,2-DIOL AS A PROTECTING AGENT FOR SYMMETRICAL DIALDEHYDE

A novel polymer-bound 1,2-diol, 3-polystyrylsulfonyl-1,2-propanediol (6) had been prepared by the reaction of sodium polystyrylsulfinate with allyl bromide, followed by oxidation and. hydrolysis or directly with 3-chloro-1,2-propanediol in the presence of a phase transfer catalyst, n-tetrabutylammonium iodide. The capacity of resin 6 for terephthaidehyde reached 1.43 mmol/g. The aldehydic groups attached to polymer 6 reacted with hydroxylamine hydrochloride or reduced by sodium borohydride giving p-formylbenzaldoxime (yield: 89%)and p-formyl-benzalcohol (yield: 734%), respectively. The high yields of these polymer-supported reactions showed that the polymer 6 possessed the effective isolation of its reactive sites.

Stereoselective cycloaddition of N-acyliminium cations withα,β-unsaturated ketones and esters

The cycloaddition of N-acyliminium cations with some deactivated alkenes such as α,β-unsaturate ketones and esters has been investigated. In most cases, the N-acyliminium cations produced from 3-hydroxy-2-arylisoindol-1-ones in the presence of BFa.OEt2 could be reacted with α,β-unsaturated ketones and esters to afford stereoselectively the cycloaddition products 6-acylisoindolo[2,1- a]quinolin-11-ones in moderate to high yields. C 2009 Wei Zhang. Published by Elsevier B.V, on behalf of Chinese Chemical Society. All rights reserved.

茯苓水提物对高尿酸血症大鼠rURAT1 rOAT1和rOCT2表达的影响

目的考察茯苓水提物对高尿酸血症大鼠肾脏组织中尿酸转运体1(rURAT1)、有机阴离子转运体1(rOAT1)和有机阳离子转运体2(rOCT2)表达的影响,探讨茯苓降低血尿酸水平的机制。方法将右侧肾脏摘除的48只大鼠随机分为6组:手术对照组、模型组、别嘌呤醇阳性对照组,茯苓水提物高、中、低剂量组。药物干预28d,实验期间定期检测血尿酸和血清肌酐水平,采用免疫印迹法检测各组大鼠肾脏组织中rURAT1、rOAT1和rOCT2的表达。结果茯苓水提物高、中、低剂量组的血尿酸水平均较模型组大鼠明显降低;肾脏组织中rOAT1和rOCT2的表达均较模型组大鼠明显升高,而其rURAT较模型组大鼠显著下降,差异均有统计学意义(P<0.05)。结论茯苓水提物通过调节肾脏组织中rURAT1、rOAT1和rOCT2的表达,从而发挥促进高尿酸血症大鼠尿酸的排泄作用。

Morphology Control over the Organic Nanoparticles of 1,3-Diphenyl-5-(9-anthryl)-2-pyrazoline

The organic nanoparticles of a blue-light-emitting molecule,1,3-diphenyl-5-(9-anthryl)-2-pyrazoline,were prepared by reprecipitation method using acetonitrile as the solvent for the molecular precursor. Three morphologies,spherical,doughnut-shaped and cubic,could be observed on the silicon substrate for the nanoparticles by the volume-controlled addition of acetonitrile. The evolution of particle morphology as a function of acetonitrile addition was attributed to the variation of the growth habits of the particles in the different environment. The nanoparticles exhibit the novel photoluminescence spectra as compared to those of monomer and the bulk crystals.

糖尿病肾病大鼠肾脏MATE1和OCT2表达及体内二甲双胍排泄变化研究

目的:研究糖尿病肾病状态下大鼠体内二甲双胍排泄的变化和肾脏中多药及毒性化合物外排转运体1(MATE1)和有机阳离子转运体2(OCT2)表达的变化,并探讨两者之间的关系。方法:雄性SD大鼠随机分为对照组(n=12)和造模组(n=12),链脲佐菌素腹腔注射诱导大鼠糖尿病肾病模型;大鼠尾静脉注射二甲双胍(10 mg/kg),考察其在大鼠体内的药物代谢动力学参数,膀胱插管实验考察大鼠体内各时间段的累积尿药排泄分数及肾清除率,测定大鼠肝脏和肾脏药物浓度;RT-qPCR和Western blot检测大鼠肾脏组织MATE1和OCT2的mRNA及蛋白表达水平。结果:与对照组相比,糖尿病肾病大鼠体内的二甲双胍血浆暴露量显著降低(P<0.01),二甲双胍清除率显著升高(P<0.01),二甲双胍在大鼠体内的稳态表观分布容积显著降低(P<0.01),平均滞留时间显著降低(P<0.01),半衰期显著缩短(P<0.05);糖尿病肾病大鼠2 h内二甲双胍的累积尿药排泄分数显著升高(P<0.05),肾清除率显著升高(P<0.01);糖尿病肾病大鼠肾脏中二甲双胍的药物浓度显著降低(P<0.05),肝脏中药物浓度无显著性差异;糖尿病肾病大鼠肾脏MATE1的mRNA表达水平显著升高(P<0.05),OCT2的mRNA水平显著降低(P<0.05),MATE1的蛋白表达水平显著升高(P<0.01),OCT2的蛋白表达水平显著降低(P<0.01)。结论:糖尿病肾病状态下大鼠肾脏MATE1表达升高,而OCT2表达下降;糖尿病肾病大鼠二甲双胍肾脏排泄的加快,可能主要与肾脏MATE1转运体表达升高相关。

OAT1/3在肾小管表达差异及竞争性抑制对急性马兜铃酸Ⅰ肾小管损伤的影响

目的 通过丙磺舒(PRB)抑制有机阴离子转运蛋白(OAT)1和3,观察马兜铃酸Ⅰ(AAⅠ)对大鼠肾小管上皮细胞的急性损伤,以探究AAⅠ进入肾小管上皮细胞的途径。方法雄性SD大鼠随机分为空白对照组、溶剂对照(PEG300)组、PRB(150 mg·kg^(-1))组、AAⅠ(80 mg·kg^(-1))组、AAⅠ(80 mg·kg^(-1))+PRB(150mg·kg^(-1))组,每2天ig给药1次,连续给药4次。观察大鼠肾脏指数;生化仪检测血清肌酐(CREA)和尿素氮(BUN)水平;苏木精-伊红(HE)染色观察肾脏组织病理学变化;免疫组化染色观察OAT1和OAT3在肾小管的组织定位和蛋白表达水平;免疫透射电镜观察OAT1和OAT3在肾小管上皮细胞的亚细胞定位和表达水平。结果 与溶剂对照组相比,AAⅠ组肾脏指数、CREA和BUN水平显著增加(P<0.01、0.001);AAⅠ+PRB组与AAⅠ组相比,肾脏指数、CREA和BUN水平显著降低(P<0.05、0.001)。HE染色结果显示,与溶剂对照组相比,AAⅠ组肾近端小管上皮细胞(PCTEC)出现空泡样变性、微绒毛脱落以及片状坏死脱落,而AAⅠ+PRB组与AAⅠ组相比,PCTEC空泡样变性率下降,无其他类型病理学变化;另外,肾远端小管上皮细胞(DCTEC)AAⅠ组与AAⅠ+PRB组呈现少量空泡样变性。免疫组化和电镜结果显示,OAT1主要在PCTEC基底膜侧表达,OAT3主要在DCTEC基底膜侧表达,且AAⅠ暴露后,与溶剂对照组比较,前者在近端小管(PCT)表达有下降趋势(P<0.05),后者在远端小管(DCT)表达有上升趋势(P<0.05)。结论 AAⅠ能够导致PCT和DCT的损伤,PRB抑制OAT1和OAT3后,能够改善肾脏功能,并减少肾小管上皮细胞的病理学损害;OAT1可能是AAⅠ进入PCTEC的主要通道,而OAT3则可能是其进入DCTEC的主要通道。

Oatp1和Oct1在大鼠下颌骨来源成骨细胞中的表达

目的:通过检测大鼠下颌骨成骨细胞中Oatp1和Oct1蛋白的表达,观察其在成骨细胞中的分布,探讨Oatp1和Oct1在成骨细胞跨膜转运中的作用及意义。方法:分离培养大鼠下颌骨成骨细胞并鉴定,应用免疫细胞化学及Western-Blot的方法检测大鼠下颌骨来源成骨细胞中Oatp1和Oct1蛋白的表达。结果:组织块法可成功培养大鼠下颌骨成骨细胞,Oatp1和Oct1在成骨细胞中有广泛表达,且主要分布在胞膜和胞质中。结论:大鼠下颌骨来源的成骨细胞可广泛表达Oatp1和Oct1,为研究药物在成骨细胞中的跨膜转运提供了基础。

去铁酮与人有机阳离子转运体及有机阴离子转运体1体外相互作用研究

目的：建立细胞裂解液中去铁酮测定的液相色谱-串联质谱（ LC-MS/MS）方法，体外考察去铁酮与人有机阳离子转运体（ hOCTs）及有机阴离子转运体1（hOAT1）的相互作用。方法：以Agilent Eclipse Plus C18柱（2．1 mm ×50 mm，3．5μm）为分析柱；0．1％甲酸-水（ v/v）和0．1％甲酸-乙腈（ v/v）为流动相，梯度洗脱；应用电喷雾离子源（ ESI源）、多反应监测（ MRM）模式进行检测；应用稳定表达hOCTs及hOAT1的细胞模型（ MDCK-hOCTs和MDCK-hOAT1）考察去铁酮对经典底物在细胞内积聚的影响；比较去铁酮在转空载体的mock细胞及MDCK-hOCTs中积聚的差异，以及经典抑制剂对其积聚的影响。结果：去铁酮在5～300 nmol/L的浓度范围内线性关系良好；准确度大于94％，日内相对标准偏差小于2％。300μmol/L去铁酮使hOCTs经典底物MPP＋在MDCK-hOCTs的积聚降低至阴性对照的70．4％～87．1％；去铁酮在MDCK-hOCTs细胞和mock细胞中的积聚无明显差别，且经典抑制剂对去铁酮的积聚无明显抑制作用；100μmol/L去铁酮对hOAT1经典底物6-CF在MDCK-hOAT1细胞中的积聚无显著影响。结论：本实验建立的方法适用于细胞裂解液中去铁酮的定量分析；去铁酮对hOCT1和hOCT3有一定的抑制作用，对hOCT2和hOAT1则无明显抑制作用；hOCTs在去铁酮跨膜转运中不起主导作用。

New insights in bilirubin metabolism and their clinical implications

Bilirubin,a major end product of heme breakdown,is an important constituent of bile,responsible for its characteristic colour.Over recent decades,our understanding of bilirubin metabolism has expanded along with the processes of elimination of other endogenous and exogenous anionic substrates,mediated by the action of multiple transport systems at the sinusoidal and canalicular membrane of hepatocytes.Several inherited disorders characterised by impaired bilirubin conjugation(Crigler-Najjar syndrome typeⅠand typeⅡ,Gilbert syndrome)or transport(Dubin-Johnson and Rotor syndrome)result in various degrees of hyperbilirubinemia of either the predominantly unconjugated or predominantly conjugated type.Moreover,disrupted regulation of hepatobiliary transport systems can explain jaundice in many acquired liver disorders.In this review,we discuss the recent data on liver bilirubin handling based on the discovery of the molecular basis of Rotor syndrome.The data show that a substantial fraction of bilirubin conjugates is primarily secreted by MRP3 at the sinusoidal membrane into the blood,from where they are subsequently reuptaken by sinusoidal membrane-bound organic anion transporting polypeptides OATP1B1 and OATP1B3.OATP1B proteins are also responsible for liver clearance of bilirubin conjugated in splanchnic organs,such as the intestine and kidney,and for a number of endogenous compounds,xenobiotics and drugs.Absence of one or both OATP1B proteins thus may have serious impact on toxicity of commonly used drugs cleared by this system such as statins,sartans,methotrexate or rifampicin.The liverblood cycling of conjugated bilirubin is impaired in cholestatic and parenchymal liver diseases and this impairment most likely contributes to jaundice accompanying these disorders.

基于高尿酸血症小鼠OCT1表达的萆薢渗湿汤降尿酸机制研究

目的:探讨萆薢渗湿汤对高尿酸血症小鼠的影响及机制。方法:昆明小鼠随机分为空白组、模型组和中药低、高剂量组,检测各组小鼠血清尿酸水平和肾、小肠和大肠各组织中OCT1表达水平。结果:与模型组比较,中药低、高剂量组小鼠血清尿酸水平明显降低,小鼠肾、小肠和大肠各组织OCT1表达量明显升高。结论:萆薢渗湿汤能明显降低小鼠血清尿酸水平,其机制可能是上调小鼠肾、小肠和大肠组织OCT1表达水平。

有机阳离子转运体3(OCT3)的生物学特点及其在相关神经精神疾病中的作用

有机阳离子转运体3(organic cation transporter 3,OCT3)是一种广泛分布于脑内的低亲和力单胺类递质转运体,也可以转运各类有机阳离子物质,最重要的特点是多在高亲和力单胺类递质转运体(即经典单胺类递质转运体)饱和或功能障碍时发挥代偿性的转运作用。OCT3可以在经典单胺类转运体功能障碍或数量减少时改变细胞内外单胺递质的水平,调节多种药物的代谢、疗效、不良反应,影响多种神经毒物的致病性和毒品的成瘾效应。该转运体的相关基因突变也影响了宿主对某些神经精神性疾病的易感性。本文先概述OCT3的蛋白分子结构、在脑内的分布、编码该分子的基因结构及翻译后调节的方式,再分别阐述该转运体底物的类型及转运机制,进而围绕OCT3的转运机制阐述其在抑郁症、应激相关性成瘾以及帕金森病(Parkinson’s disease,PD)中的作用。

The influence of OCT1 gene polymorphisms on the metformin response in Uygur patients with glucose metabolism disorder

Objective To determine the effects of genetic variation in the organic cation transporter 1(OCT1)on the short-term responses of the antidiabetic drug,metformin.Method A total of 22 patients recruited with type 2 diabetes or IFG were treated with metformin(2 000 mg/day)for 1 week.The patients were screened from Second Jikun hospital and Kashidonglu community medicine service,Urumqi,China and their surrounding districts.To examine the effects of metformin on plasma glucose,total cholesterol,low-density lipoprotein-cholesterol,high-density lipoprotein-cholesterol and triglyceride in relation with R61C,G465R and 420 del variants of OCT1(gene encoding organic cation transporter 1,mainly locating in liver,which is metformin's major target)in subjects.In all,R61C,G465R and 420del of OCT1 gene were examined using DNA extracted from whole blood and PCR-RFLP.Data concerning with gene and metformin treatment were handled by t-test.Result After metformin treatment,there were increases both in FPG and LDL(P=0.011and P=0.013 respectively).To divide all participants into mutant and wild groups,according to the polymorphisms of R61C,G465R and 420 del respectively,as well as carriers with one of the mutant genotypes at least and carriers with none of the mutant sites.Analysis was made to compared FPG,Chol,TG,and LDL and HDL between carriers of wild genotypes and carriers of other genotypes showed no statistic significance both before the metformin treatment and after the treatment.The same is the case with changes of FPG,Chol,TG,and LDL and HDL of wild genotype carriers and variant genotype carriers,except of LDL changes(P=0.05)in patients grouped by G465R polymorphisms and TG changes(P=0.03)in subjects differed by 420del genotypes.Conclusion In this study,it is suggested that OCT1 gene polymorphisms have little contribution to the clinical efficacy of blood glucose control by metformin among Uygur people with type 2 diabetes or IFG,but it may have possible relationship with the clinical efficacy on fat metabolism by metformin.

缺氧预处理对创伤性脑损伤大鼠缺氧诱导因子-1α、葡萄糖转运体3型及神经元核蛋白表达的影响

目的探讨缺氧预处理(HPC)对创伤性脑损伤(TBI)大鼠挫伤灶周围皮层组织中缺氧诱导因子-1α(HIF-1α)、葡萄糖转运体3型(GLUT-3)表达及神经元存活影响。方法 120只Sprague-Dawley大鼠按随机数字法分为对照组(12只)、TBI组(54只)、HPCT组(54只)。TBI组按Feeney自由落体撞击法建立大鼠TBI模型,HPCT组先给予3 d HPC(50.47 k Pa,3 d,3 h/d),之后同法致伤。采用RT-PCR及Western blotting检测伤后1、4、8、12 h及1、3、7、14 d挫伤灶周围HIF-1α、GLUT-3 m RNA及蛋白的表达,并分析HIF-1α与GLUT-3之间的相关性,采用免疫组化检测伤后14 d挫伤灶周围神经元核蛋白(Neu N)阳性表达率来观察神经元存活情况。多组间比较行单因素方差分析,用LSD法行两两比较分析2组间差异,相关性分析用Pearson相关分析,以P<0.05为差异具有统计学意义。结果 TBI组伤后4 h至3 d HIF-1α、GLUT-3的表达均明显增加(P<0.05)。HPCT组HIF-1α及GLUT-3的表达在伤后1 h即增强,伤后4 h至7 d HIF-1α、GLUT-3表达量和伤后14 d Neu N阳性细胞数均明显高于TBI组,差异均具有统计学意义(P<0.05)。相关性分析表明HIF-1α与GLUT-3 m RNA及蛋白的表达均呈正相关。结论 HPC可通过诱导皮层脑组织HIF-1α的表达,上调GLUT-3 m RNA及蛋白的表达,进而提高TBI后急性期神经元的存活率。

醋柴胡多糖对拉米夫定体外抗乙型肝炎病毒的增效作用研究

目的:考察醋柴胡多糖对拉米夫定抗乙型肝炎病毒(HBV)的增效作用,并初步探讨其作用机制。方法:将不同浓度的醋柴胡多糖、拉米夫定及二者联合作用于人肝癌细胞HepG2.2.15,同时设立对照组,孵育48 h,酶联免疫吸附试验试剂盒检测细胞上清液中乙型肝炎表面抗原(HBsAg)、乙型肝炎e抗原(HBeAg)分泌量,荧光探针定量聚合酶链式反应(PCR)检测细胞HBV脱氧核糖核酸(DNA)表达量,金(正均)氏公式定量分析醋柴胡多糖的增效作用。采用高效液相色谱法测定细胞内拉米夫定含量;Western blot法测定有机阳离子转运蛋白(OCT)1、OCT2、P糖蛋白(P-gp)和多药耐药蛋白2(MRP2)的表达量。结果:与拉米夫定单用组相比,醋柴胡多糖增加拉米夫定对HBsAg分泌的抑制作用,表现为相加作用、对HBeAg作用表现为协同增强,Q值达6.55、对HBV-DNA抑制作用表现为相加。醋柴胡多糖低剂量组、醋柴胡多糖低中剂量组、醋柴胡多糖低高剂量组可显著促进拉米夫定的摄取;醋柴胡多糖高剂量联用组可显著降低P-gp的表达;醋柴胡多糖单用及联用组均可显著提高OCT1的表达。结论:醋柴胡多糖可通过增加拉米夫定的摄取发挥协同抗HBV作用,其作用机制可能P-gp、OCT1有关。