蓝莓对免疫性肝纤维化大鼠细胞色素P4502E1表达的影响

目的 观察蓝莓对大鼠免疫性肝纤维化的预防作用及其对细胞色素P4502E1 (CYP2E1)表达的影响.方法 将50只健康清洁级Wistar大鼠随机分为正常对照组(A组)、肝纤维化模型组(B组)、蓝莓原浆预防组(C组)、复方鳖甲软肝片预防组(D组)、蓝莓原浆加复方鳖甲软肝片预防组(E组)共5组,每组10只.除正常对照组外,其余各组均腹腔注射猪血清制备大鼠肝纤维化模型,各预防组在造模同时分别给予蓝莓原浆或(和)复方鳖甲软肝片灌胃,1次/d,共12周.12周末处死大鼠,行肝脏病理组织学检查,测定各组大鼠血清ALT水平、肝组织匀浆超氧化物歧化酶(SOD)活性、丙二醛(MDA)及羟脯氨酸(Hyp)含量,采用实时荧光定量聚合酶联反应、Western blot和免疫组织化学法检测大鼠肝组织CYP2E1的mRNA及蛋白质表达. 结果 12周末处死大鼠,A、B、C、D、E各组大鼠血清ALT水平分别为(37.9±4.5) U/L、(49.2±9.8) U/L、(39.9±6.3) U/L、(40.5±5.7) U/L及(38.2±8.4)U/L,各组间差异无统计学意义;各预防组大鼠肝纤维化程度较B组明显减轻(F=95.097,P＜0.05); C、D、E各组大鼠肝组织匀浆Hyp分别为(472.7±44.1)μg/g、(416.1±39.4)μg/g和(429.5±55.1)μg/g,低于B组的(603.2±68.9) μg/g,F=39.315,P＜0.05,差异有统计学意义; SOD水平分别为(2.5±0.4) U/mg、(2.0±0.5)U/mg、(2.2±0.2) U/mg,高于B组的(1.6±0.4) U/mg,F=25.557,P＜0.05,差异有统计学意义;MDA分别为(0.83±0.06) mol/mg、(0.96±0.08) nmol/mg、(0.85±0.06)nmol/mg,低于B组的(1.24±0.15)nmol/mg,F=46.376,P＜0.05,差异有统计学意义;B、C、D、E组大鼠肝组织CYP2E1的mRNA及蛋白质表达高于A组,C、D、E组大鼠肝组织CYP2E1的mRNA及蛋白质表达低于B组,但差异均无统计学意义.结论 蓝莓对猪血清所致大鼠肝纤维化有一定的预防作用;免疫性肝纤维化时,大鼠肝组织CYP2E1的表达无明显改变;蓝莓对CYP2E1的表达无明显影响.     

酒精性肝病细胞色素P4502E1基因多态性研究

目的 探讨细胞色素P4502E1(CYP2E1)基因多态性与酒精性肝病(ALD)的关系.方法 将2004年10月至2005年10月兰州大学第一医院消化科住院及门诊患者80例分为ALD组(40例)和非ALD组(40例)以及健康体检中心103名体检者分为嗜酒组(40名)和正常组(63名).ALD组与嗜酒组患者均饮酒＞80 g/d,连续10年以上.非ALD组和正常组均不饮酒.采用聚合酶链反应-限制性片段长度多态性分析法(PCR-RFLP)检测ALD组、非酒精性肝病组、嗜酒组、正常组中CYP2E1的基因多态性,并进行相关性分析.结果 ALD组中C2等位基因型与对照组相比明显升高,P＜0.001,差异有显著性意义;在ALD组中随肝纤维化指标异常程度增加,C2基因型明显升高,差异具有显著性意义,P＜0.05.结论 ALD与CYP2E1基因相关,CYP2E1等位基因C2可能是ALD的危险因素.     

大鼠酒精性肝病细胞凋亡与细胞色素P4502E1和氧化应激的关系

目的:观察大鼠酒精性肝病组织病理形态学改变,探讨细胞凋亡与细胞色素P4502E1的表达以及和氧化应激的关系.方法:用酒精灌胃法制备酒精性肝病大鼠模型,模型组给予酒精8 g/kg,每天分2次灌胃连续8 wk,对照组给予等量的生理盐水灌胃.实验8 wk末,观察肝组织的病理形态学改变,用原位末端标记法(TUNEL)检测肝细胞凋亡,用免疫组化法检测肝组织中Caspase-3蛋白表达,用全自动生化仪检测ALT和AST的含量,用PCR法测定肝细胞色素P4502E1的基因表达,分别用硫代巴比妥酸法(TBA法)和黄嘌呤氧化酶法测定肝组织丙二醛(MDA)的含量和超氧化物歧化酶(SOD)的活力.结果:模型组凋亡的肝细胞明显增多,主要分布在中央静脉周围、点状和灶状坏死区;Caspase-3主要分布于中央静脉及肝细胞坏死灶周围细胞的胞质中.模型组肝细胞凋亡指数(AI)和Caspase-3蛋白表达强度明显高于对照组(AI:6.2%±1.7% vs 1.7%±0.8%;Caspase-3:66.7% vs 9.5%,P<0.05,P<0.01).CYP2E1表达:对照组c1基因频率为91.6%,c2基因频率为8.4%;模型组c1基因频率为53.4%,c2基因频率为46.6%,均有显著性差异(P<0.05).长期酒精摄入大鼠血清MDA含量增加(41.53±7.43μmol/L vs 15.72±2.06μmol/L,P<0.05),SOD活力下降(353.12±61.02 kU/L vs 636.82±138.60 kU/L,P<0.05),与酒精性肝病肝细胞凋亡程度有相关性(r=0.644,r=-0.511).结论:长期酒精摄入可引起大鼠酒精性肝病及及肝功能损伤,肝细胞凋亡明显增加.CYP2E1基因PstⅠ及RsaⅠRFLPs与酒精性肝病有关,其中c2基因可能与大鼠酒精性肝病的发生有关.MDA含量和SOD活力在酒精性肝病的肝细胞凋亡过程及脂质过氧化反应中发挥重要作用.     

细胞色素P4502E1酶与非酒精性脂肪肝的关系

目的:探讨细胞色素P4502E1(CYP2E1)酶基因多态性与非酒精性脂肪性肝病(NAFLD)的关系及NAFLD的遗传学发病机制.方法:采用聚合酶链反应——限制性片段长度多态性分析法(PCR-RFLP)对40例非酒精性脂肪肝患者,20例酒精性肝病患者,20例非脂肪肝对照者,20例正常对照者分析CYP2E1基因多态性,并进行相关性分析.结果:NAFLD中c2等位基因型与正常对照组(x~2=8.376,P=0.004)和非脂肪肝对照组(x~2= 6.769,P=0.005)相比明显升高,差异有统计学意义(P<0.01),NAFLD中基因型分布与酒精性肝病相比无明显改变,差异无统计学意义(P =0.896).在NAFLD中肝脏病变程度不同,c2等位基因频率不同,在脂肪性肝炎(P=0.04)和肝硬化(P=0.000)中,差异有统计学意义(P<0.05).结论:NAFLD与CYP2E1酶基因多态性有关,同时也为研究NAFLD遗传易感性提供了新的思路.     

细胞色素P4502E1基因在肝脏疾病中的意义

细胞色素Ｐ4 50 (ｃｙｔｏｃｈｒｏｍｅＰ4 50 ,ＣＹＰ)是一组结构和功能相关的基因编码的同工酶 ,其特征是与ＣＯ结合后在 4 50ｎｍ处有吸收峰的含血红素的单链蛋白质。其主要功能是对内源性及外源性化合物进行生物转化。一些疏水性外来物质 ,经ＣＹＰ转化后形成极性更大的物质 ,排出体外。某些情况下可能被转化为细胞毒、致癌、致突变作用更强的物质。因此 ,ＣＹＰ的生物学效应具有双重性。其中ＣＹＰ2Ｅ1是二甲基亚硝胺Ｄ -脱甲基酶 ,它不仅参与药物的代谢 ,而且还催化许多前致癌物和前毒物的活化过程。其活性存在明显的个体差异。本文对…     

细胞色素酶P4502E1介导的氧化应激对人肝星状细胞的活化作用

目的 研究细胞色素酶P4502E1(CYP2E1)介导的氧化应激对人肝星状细胞的活化作用. 方法 以CYP2E1为目的 基因,将CYP2E1表达载体PCI-CYP2E1及空载体PCI-neo转染到人肝癌细胞株HepG2细胞,分别为HepG2/CYP2E1,HepG2/PCI.检测HepG2/CYP2E1,HepG2/PCI及正常HepG23组细胞上清液中丙二醛(MDA)含量.将上述3种细胞分别与人肝星状细胞LX2共培养48 h,分别命名为CYP2E1/LX2组,PCI/LX2组,HepG2/LX2组,提取RNA、上清液,用羟脯氨酸(Hyp)试剂盒检测3组LX2上清液中Hyp含量,用逆转录多聚酶链反应检测LX2细胞内Ⅰ型胶原、基质金属蛋白酶2(MMP2)的mRNA水平,用酶联免疫吸附试验检测3组上清液中LX2分泌的Ⅰ型前胶原羧基肽(PICP)蛋白水平,用明胶酶谱法检测3组上清液中LX2分泌的MMP2酶活性.组间比较用单因素方差分析进行统计学分析. 结果 (1)HepG2/CYP2E1细胞、阴性对照组HepG2细胞及HepG2/PCI细胞的MDA值分别为(6.51±0.25)nmol/ml、(3.07±0.29)nmol/ml和(2.57±0.29)nmol/ml,F值为22.66,P值均<0.01.(2)HepG2/CYP2E1、HepG2、HepG2/PCI 3组细胞培养液中Hyp含量分别为(35.24±3.52)nmol/ml、(24.50±1.37)nmol/ml和(17.77±2.58)nmol/ml,F值为58.89,P值均<0.01; 3组LX2细胞Ⅰ型胶原mRNA水平表达,差异无统计学意义.CYP2E1/LX2组、阴性对照组HepG2组及PCI/LX2组LX2分泌的PICP蛋白吸光度值分别为540.01±11.38、262.57±15.61和231.59±12.76,F值为124.97,P值均<0.01; 3组LX2细胞内MMP2 mRNA水平表达、MMP2的酶活性,差异无统计学意义. 结论 CYP2E1可引起氧化应激,CYP2E可增加LX2细胞外Hyp的合成和分泌.CYP2E1活化了肝星状细胞,可促进其细胞外PICP合成与分泌.     

非酒精性脂肪性肝炎肝细胞内细胞色素P450ⅡE1的表达

目的　探讨非酒精性脂肪性肝炎（ＮＡＳＨ）肝组织内细胞色素Ｐ４５０ Ⅱ　Ｅ１（ＣＹＰ　Ⅱ　Ｅ１）的表达情况。方法　采用抗生蛋白链菌素－过氧化酶法（ＳＰ）检测ＮＡＳＨ大鼠肝组织ＣＹＰ　Ⅱ Ｅ１的表达情况。同时常规苏木素伊红染色观察肝脏病理学变化。结果ＮＡＳＨ模型组动物ＣＹＰ ⅡＥ_１阳性细胞显著增加；且多在中央静脉周围，这与肝脂肪性变趋于一致。结论 ＮＡＳＨ肝组织中存在着ＣＹＰ Ⅱ　Ｅ_１的高表达。     

复方中药对酒精性脂肪肝肝细胞色素P450ⅡE1表达的影响

目的 研究复方中药对酒精性脂肪肝肝细胞色素P450ⅡE1(CYPⅡE1)表达的影响。 方法 在大鼠饮水中逐步加入40％的乙醇(v/v)形成酒精性脂肪肝模型,同时给予复方中药干预,观察肝组织病理形态的变化和肝CYPⅡE1的表达,测定肝丙二醛(MDA)和超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、维生素E含量的变化,并与对照组比较。 结果 中药组的肝组织脂肪变性基本恢复正常,免疫组织化学和原位杂交证明复方中药能显著抑制脂肪肝肝CYPⅡE1的表达,同时肝内MDA和SOD、GSH、维生素E含量恢复到接近正常。 结论 复方中药能显著抑制酒精性脂肪肝肝CYPⅡE1的表达,具有防止酒精性脂肪肝的作用。     

非酒精性脂肪肝大鼠肝细胞色素P450 2E1基因及表达变化的意义

细胞色素P450 2E1(cytochrome P450 2E1,CYP 2E1),是细胞色素P450的乙醇诱导形式,它在非乙醇脱氢酶氧化途径中起重要作用,为酒精性肝病的主要发病机制。CYP 2E1基因及多型性与酒精性肝病的发生有密切关系,通过高脂饲料诱导的大鼠脂肪肝模型,探讨在脂肪肝的发展过程中肝CYP 2E1基因及表达变化规律,为脂肪肝的发生和治疗提供理论基础。     

表达细胞色素P2E1 C3A肝细胞系的建立及其对增殖的影响

细胞色素P450 2E1（Cytochrome-P450）2E1,CYP2E1）在非酒精性脂肪性肝病（NAFLD）的发病机制中发挥重要作用.CYP2E1广泛与细胞物质代谢,是否影响肝细胞增殖是一个值得探讨的问题,我们对CYP2E1对C3A肝细胞增殖的影响进行了初步探索.     

Expression of cytochrome P4502E1 gene in hepatocellular carcinoma

AIM: To investigate cytochrome P4502E1 (CYP2E1) gene expression in occurrence and progression of hepatocellular carcinoma (HCC). METHODS: The human liver arrayed library was spotted onto the nylon membranes to make cDNA array. Hybridization of cDNA array was performed with labeled probes synthesized from RNA isolated from HCC and adjacent liver tissues. Sprague-Dawley rats were administrated diethylnitrosamine (DENA) to induce HCC. CYP2E1 expression was detected by the method of RT-PCR and Northern blot analysis. RESULTS: CYP2E1 was found by cDNA array hybridization to express differently between HCC and liver tissues. CYP2E1 only expressed in liver, but did not express in HCC tissues and expressed lowly in cirrhotic tissues. In the progression of cirrhosis and HCC, the expression level of CYP2E1 was gradually decreased and hardly detected until the late stage of HCC. CONCLUSION: Using arrayed library to make cDNA arrays is an effective method to find differential expression genes. CYP2E1 is a unique gene expressing in liver but did not express in HCC. CYP2E1 expression descended along with the initiation and progression of HCC, which is noteworthy further investigations in its significance in the development of HCC.     

肝细胞色素P450 1A1、2E1在非酒精性脂肪肝发病中的作用

目的　研究肝细胞色素P4 5 0 1A1、2E1在非酒精性脂肪肝大鼠中的表达及其意义。方法　荧光分光光度计法检测高脂饲料诱导 4 0只大鼠脂肪肝模型中P4 5 0 1A1活性 (7 乙氧异唑O 脱乙基酶 ,EROD)和 2E1活性 (苯胺羟化酶 ,ANH) ,免疫组化和Westernblot方法测定肝细胞色素P4 5 0 1A1、2E1表达 ,逆转录聚合酶链反应测定其mRNA表达。结果　脂肪肝 2、4、8和 1 2周EROD活性分别为(32 5 .0 7± 5 9.6 8)、(345 .2 5± 4 9.2 8)、(4 6 8.95± 5 5 .2 8)和 (5 4 8.6 8± 4 3.2 5 )nmol·mg-1 ·min-1 ,与正常对照组的 (2 6 0 .4 2± 35 .32 )nmol·mg-1 ·min-1 比较明显增高 (P <0 .0 1 ) ,脂肪肝 2、4、8和 1 2周ANH活性分别为 (6 35 .6 8± 6 5 .4 8)、(735 .4 5± 76 .89)、(887.4 5± 85 .6 5 )和 (95 6 .5 8± 84 .4 7)nmol·mg-1 ·min-1 ,与正常对照组的 (5 0 0 .2 5± 78.34)nmol·mg-1 ·min-1 比较明显增高 (P <0 .0 1 ) ,肝细胞色素P4 5 0 1A1、2E1基因表达随脂肪肝程度的加重而增高。结论　脂肪肝引起的肝脏损害可能与肝细胞色素P4 5 0 1A1、2E1表达有关 ,两者共同参与脂肪肝的发生     

Chlorzoxazone pharmacokinetics as a marker of hepatic cytochrome P4502E1 in humans

Objective: Previous in vitro studies have demonstrated that hepatic P4502E1 metabolizes chlorzoxazone (CZX, a commonly used muscle relaxant) to 6-hydroxychlorzoxazone (6-OH-CZX). We thus assessed whether measurement of the plasma 6-OH-CZX/CZX ratio after a CZX challenge could serve as a marker of hepatic P4502E1 content.
Methods: Three subject groups were included: recently drinking alcoholics (  N = 6  ), abstinent alcoholics (  N = 5  ), and nonalcoholic subjects with liver disease (  N = 5  ) undergoing liver biopsy. Excess tissue was procured for immunochemical determination of hepatic P4502E1 content. Within an hour of the biopsy, 750 mg CZX was administered orally and serial plasma samples were collected for 6 h.
Results: Recently drinking alcoholic subjects had a higher area under the curve for plasma 6-OH-CZX (1.354 ± 0.258 μg · min · ml⁻¹) then abstinent alcoholic subjects (0.296 ± 0.080 μg · min · ml⁻¹, p < 0.005) and subjects with nonalcoholic liver disease (0.428 ± 0.061 μg · min · ml⁻¹,   p < 0.005  ). The use of the plasma 6-OH-CZX/CZX ratio at 90, 120, and 180 min discriminated between recently drinking alcoholic and nondrinking subjects. Hepatic P4502E1 content significantly correlated with the maximal 6-OH-CZX concentration (  r = 0.76  , p = 0.001) and other pharmacokinetic parameters. In the recently drinking group, the area under the curve for plasma 6-OH-CZX significantly decreased after 8 days of abstinence.
Conclusions: Measurement of plasma 6-OH-CZX after administration of a CZX challenge can serve as a marker of hepatic P4502E1 activity and thus help avoid adverse drug reactions secondary to P4502E1 induction, particularly in heavy drinkers.     

非酒精性脂肪肝大鼠肝细胞色素P450 1A1基因及表达变化的意义

目的研究非酒精性脂肪肝大鼠肝细胞色素P450 1A1基因和表达变化及其意义.方法雄性Wistar大鼠40只,随机分为两组,正常对照组8只,高脂饮食组2、4、8、12各8只,紫外分光光度计法检测P450 1A1活性(7-乙氧异恶唑0-脱乙基酶,EROD);免疫组织化学和Western blot方法测定肝细胞色素P450 1A1表达变化,逆转录聚合酶链反应测定肝细胞色素P450 1A1 mRNA表达变化.结果脂肪肝2、4、8和12周EROD活性分别为325.07±59.68、345.25±49.28、468.95±55.28和548.68±43.25 nmol·mg-1·min-1,与正常对照组260.42±35.32 nmol·mg-1·min-1比较明显增高(P＜0.01),肝细胞色素P450 1A1基因及蛋白表达随着脂肪肝程度的加重明显增强.结论非酒精性脂肪肝大鼠肝细胞色素P450 1A1基因和表达变化与脂肪肝引起的肝脏损害程度密切相关.     

Ethanol enhances retinoic acid metabolism into polar metabolites in rat liver via induction of cytochrome P4502E1

BACKGROUND & AIMS: Long-term and excessive ethanol intake results in decreased plasma and hepatic levels of retinoic acid (RA), the most active derivative of vitamin A. The decrease of RA by ethanol treatment has been proposed to be a cytochrome P450 enzyme (CYP)-dependent process. However, the role of the major ethanol-induced CYP, CYP2E1, in the metabolism of RA has not been defined. METHODS: In vitro incubations of RA with microsomal fractions of liver tissue containing CYPs from either ethanol-exposed or non-ethanol-exposed rats were carried out using chemical inhibitors and antibodies against various CYPs. In vivo, both ethanol-exposed and non-ethanol-exposed rats were treated with or without chlormethiazole, a specific CYP2E1 inhibitor, for 1 month. RA and its catabolic metabolites were analyzed by high-performance liquid chromatography and spectral analysis. RESULTS: Incubation of RA with the liver microsomal fraction from ethanol-exposed rats resulted in greater disappearance of RA and increased appearance of 18-hydroxy-RA and 4-oxo-RA compared with control rat liver microsomal fractions. The enhancement of RA catabolism by ethanol was inhibited by both CYP2E1 antibody and specific inhibitors (allyl sulfide and chlormethiazole) in a dose-dependent fashion, whereas the metabolism of RA into polar metabolites was abolished completely by nonspecific CYP inhibitors (disulfiram and liarozole). Furthermore, treatment with chlormethiazole in ethanol-fed rats in vivo restored both hepatic and plasma RA concentrations to normal levels. CONCLUSIONS: Ethanol-induced CYP2E1 plays a major role in the degradation of RA, which may provide a possible biochemical mechanism for chronic and excessive ethanol intake as a risk for both hepatic and extrahepatic cell proliferation and carcinogenesis.     

肝细胞色素P450 2E1在大鼠非酒精性脂肪肝形成中的作用

目的 研究肝细胞色素P450 2E1在大鼠非酒精性脂肪肝形成中的作用。方法 Wistar大鼠40只，随机分为正常对照组和高脂饲料2、4、8和12周组(其中每组各8只)：HE染色光镜观察肝脏组织病理改变；硫代巴比妥酸法测定肝脏组织丙二醛(MDA)的含量变化：免疫组织化学和Westemblot方法研究高脂饲料诱导的大鼠脂肪肝形成中肝细胞色素P450 2E1表达变化。结果 高脂饲料组大鼠肝脏内MDA含量明显高于对照组，随时间延长，逐渐增加：随着脂肪肝程度的加重，MDA含量逐渐增强，肝细胞色素P450 2E1蛋白表达亦明显增强。结论 非酒精性脂肪肝大鼠肝细胞色素P450 2E1表达变化与脂肪肝引起的脂质过氧化损伤程度密切相关。     

Detection of auto-antibodies against cytochrome P4502E1 (CYP2E1) in chronic hepatitis C

BACKGROUND/AIMS: Chronic hepatitis C (CHC) is often associated with auto-immune reactions. In the light of the role of alcohol in promoting CHC progression, we have investigated the possible presence of auto-reactivity against the ethanol-inducible cytochrome P4502E1 (CYP2E1) in CHC patients with and without alcohol consumption. METHODS: The IgG reactivity against recombinant human CYP2E1 was evaluated by solid-phase immunoassays in 102 CHC patients with different alcohol consumption and 59 HCV-free controls. RESULTS: Auto-antibodies against CYP2E1 were significantly (p<0.0001) increased in CHC patients as compared to controls. Anti-CYP2E1 IgG above the 97th percentile in the controls were evident in 41 (40%) CHC patients. Competition experiments revealed that CYP2E1 recognition was not due to the cross-reactivity with CYP2D6. The detection of anti-CYP2E1 IgG was unrelated to alcohol consumption and no difference in gender, age, aminotransferase levels and virus genotype was evident among the patients with or without anti-CYP2E1 auto-antibodies. However, anti-CYP2E1 auto-reactivity was significantly (p=0.025) associated with the severity of periportal/periseptal interface hepatitis. Moreover, confocal microscopy demonstrated that anti-CYP2E1 IgG associated with CHC recognized CYP2E1 exposed on the outer side of hepatocyte plasma membranes. CONCLUSIONS: HCV infection favours the breaking of self-tolerance against CYP2E1 that might contribute to hepatocyte injury.     

非酒精性脂肪肝肝细胞色素P450ⅡE1的表达与氧化抗氧化的关系

目的研究非酒精性脂肪肝肝细胞色素Ｐ４５０ⅡＥ１表达及与氧化抗氧化的关系。方法用免疫组织化学的方法研究高脂饲料诱导的大鼠脂肪肝肝细胞色素Ｐ４５０ⅡＥ１的表达,同时检测肝组织中雨二醛（ＭＤＡ）和超氧化物歧化酶（ＳＯＤ）、谷胱甘肽（ＧＳＨ）、维生素Ｅ（ＶｉｔＥ）含量的变化,并分析其相关性。结果高脂饲料诱导的大鼠脂肪肝肝细胞色素Ｐ４５０ⅡＥ１在腺泡３区的表达增强,并从３区弥散至２区,与正常组相比,脂肪肝肝组织中ＭＤＡ的含量显著升高（Ｐ＜０．０１）．而ＳＯＤ、ＧＳＨ、ＶｉｔＥ的含量显著下降（Ｐ值分别小于０．０１、０．０５、０．０１）。相关分析表明,肝ＣＹＰＨＥＩ的表达与ＭＤＡ呈非常显著的正相关（Ｐ＜０．０１）、而与ＳＯＤ、ＧＳＨ、ＶｉｔＥ呈显著的负相关ｕ值分别小于０．０５、０．０５、０．０１）。结论非酒精性脂肪肝肝细胞色素Ｐ４５０ⅡＥ１在腺泡３区的表达增强,并呈弥散性的分布,与酒精性脂肪肝的表达相似,并可能与脂质过氧化反应有关。