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Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1
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作者 Si Zou Yetao Gong +4 位作者 Xiujie Li Yanbin Wu Jinzhong Wu Jianguo Wu Ka-Hing Wong 《Food Science and Human Wellness》 SCIE CSCD 2024年第2期932-945,共14页
Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic ac... Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications. 展开更多
关键词 pTR-SeNps(polysaccharide-proteincomplex functionalized selenium nanoparticles) Acetaminophen-induced hepatotoxicity Nuclear factor erythroid 2-related factor 2 cytochrome p450 enzyme 2e1 Mitochondria
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CYP2E1-RsaⅠ、GSTT1基因多态性与胰腺癌遗传易感性的病例对照研究 被引量:4
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作者 张超贤 郭晓凤 许晓芳 《西安交通大学学报(医学版)》 CAS CSCD 北大核心 2010年第2期200-204,共5页
目的探讨吸烟和细胞色素P4502El-RsaⅠ(CYP2E1-RsaⅠ)、谷胱甘肽硫转移酶T1(GSTT1)基因多态性与胰腺癌发病之间的关系。方法采用病例-对照研究的方法,以150例胰腺癌患者及150例非癌对照者的外周血白细胞为样本,利用聚合酶链反应(po... 目的探讨吸烟和细胞色素P4502El-RsaⅠ(CYP2E1-RsaⅠ)、谷胱甘肽硫转移酶T1(GSTT1)基因多态性与胰腺癌发病之间的关系。方法采用病例-对照研究的方法,以150例胰腺癌患者及150例非癌对照者的外周血白细胞为样本,利用聚合酶链反应(polymerase chain reaction,PCR)技术分析了Ⅰ相代谢酶CYP2E1-RsaⅠ和Ⅱ相代谢酶GSTT1基因多态性。结果CYP2E1-RsaⅠ野生纯合型(c1/c1)和GSTT1基因缺陷型[GSTT1(-)]频率分布分别为38.7%、69.3%(病例组)和20.7%、44.7%(对照组),二者经χ2检验差异有显著性(χ2=15.75,P〈0.01;2χ=18.62,P〈0.01)。c1/c1基因型者患胰腺癌的风险显著增加(OR=3.19,95%CI=2.534.26)。GSTT1(-)者患胰腺癌的风险也显著增加(OR=2.85,95%CI=1.924.64)。基因突变的协同分析发现CYP2E1-RsaⅠ(c1/c1)/GSTT1(-)在胰腺癌组和对照组中的分布频率分别为30.7%和6.7%,二者经2χ检验有显著性差异(2χ=42.39,P〈0.01)。CYP2E1-RsaⅠ(c1/c1)/GSTT1(-)患胰腺癌的风险显著增加(OR=16.63,95%CI=8.9422.01)。病例组的吸烟率显著高于对照组的吸烟率(OR=2.74,95%CI=1.324.58,P〈0.01),CYP 2E1-RsaⅠ(c1/c1)及GSTT1(-)与吸烟有协同作用(OR=8.84,95%CI=5.5111.62;OR=20.40,95%CI=4.9829.53)。结论CYP2E1-RsaⅠ(c1/c1)和GSTT1(-)是胰腺癌的易患因素,二者对胰腺的发生有协同作用,吸烟与胰腺的易感性也有关,CYP2E1-RsaⅠ(c1/c1)、GSTT1(-)与吸烟在胰腺癌的发生上也有相互促进作用。 展开更多
关键词 胰腺癌 细胞色素p4502el-RsaⅠ(cyp2e1-RsaⅠ) 谷胱甘肽硫转移酶T1(GSTT1) 多态现象 吸烟
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CYP2E1和GST基因多态性对二甲基甲酰胺代谢及毒性的影响 被引量:7
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作者 徐承敏 钱亚玲 张幸 《中国工业医学杂志》 CAS 北大核心 2007年第1期38-41,共4页
二甲基甲酰胺(DMF)是一种广泛应用的工业原料。DMF的毒性与其在体内的代谢过程有关。CYP2E1是DMF的主要Ⅰ相代谢酶,Ⅱ相代谢酶谷胱甘肽-S-转移酶(glutathione S-transferase,GST)则可能在DMF的解毒过程中起重要作用。代谢酶的基因多态... 二甲基甲酰胺(DMF)是一种广泛应用的工业原料。DMF的毒性与其在体内的代谢过程有关。CYP2E1是DMF的主要Ⅰ相代谢酶,Ⅱ相代谢酶谷胱甘肽-S-转移酶(glutathione S-transferase,GST)则可能在DMF的解毒过程中起重要作用。代谢酶的基因多态性对毒物的代谢及毒作用有较大的影响。本文就CYP2E1和GST基因多态性与DMF的代谢及毒性的关系进行综述。 展开更多
关键词 二甲基甲酰胺 细胞色素p4502e1(cyp2e1) 谷胱甘肽-S-转移酶(GST) 基因多态性
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中国人群细胞色素CYP2E1基因多态性与肝癌易感性的Meta分析
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作者 周信娟 黄天壬 《中国癌症防治杂志》 CAS 2010年第4期273-275,共3页
目的探讨细胞色素P4502E1(CYP2E1)基因多态性与肝癌易感性的关系。方法计算机检索CBM、CNKI、VIP、Pubmed、Ovid等数据库,收集有关中国人群CYP2E1基因多态性与肝癌易感性的病例对照研究,以病例组和对照组CYP2E1基因型分布的比值比(od... 目的探讨细胞色素P4502E1(CYP2E1)基因多态性与肝癌易感性的关系。方法计算机检索CBM、CNKI、VIP、Pubmed、Ovid等数据库,收集有关中国人群CYP2E1基因多态性与肝癌易感性的病例对照研究,以病例组和对照组CYP2E1基因型分布的比值比(odds ratio,OR)为效应指标,对文献进行评价筛选、异质性检验,应用RevMan4.3软件对各研究原始数据进行统计,计算合并OR值及95%可信区间(confidential interval,CI)。结果最终纳入5篇病例对照研究,其中肝癌患者789例,对照864例,Meta分析结果OR及95%CI为1.15(0.94~1.41),说明CYP2E1基因型分布与肝癌的关联性无统计学意义。结论虽然中国人群CYP2E1基因型频率分布可能与患肝癌风险增加有关,但目前相关研究结果的Meta分析尚不能得出单一基因CYP2E1是肝癌易感性基因的肯定结论,需进一步开展严格设计的流行病学研究加以证实。 展开更多
关键词 细胞色素p4502e1(cyp2e1) 基因多态性 肝癌 MeTA分析
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细胞色素P4502E1及其基因多态性与酒精依赖的关系 被引量:3
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作者 黄佩佩 吕丽 刘传新 《四川精神卫生》 2020年第1期92-96,共5页
本文通过对细胞色素P4502E1(CYP2E1)及其基因多态性与酒精依赖的关系进行综述,以期为酒精依赖的早期干预提供参考。本文介绍了与酒精依赖相关的CYP2E1基因多态性以及与CYP2E1相关的酒精性疾病,在中国知网、万方、PubMed数据库检索相关文... 本文通过对细胞色素P4502E1(CYP2E1)及其基因多态性与酒精依赖的关系进行综述,以期为酒精依赖的早期干预提供参考。本文介绍了与酒精依赖相关的CYP2E1基因多态性以及与CYP2E1相关的酒精性疾病,在中国知网、万方、PubMed数据库检索相关文献,总结当前研究可能存在的不足,为后续研究提供参考。 展开更多
关键词 细胞色素p4502e1 cyp2e1 基因 酒精依赖 综述
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Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat 被引量:17
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作者 Wei Jiang Mei-Hua Guo Xin Hai 《World Journal of Gastroenterology》 SCIE CAS 2016年第46期10180-10188,共9页
AIM To evaluate the hepatoprotective effect of lycopene(Ly) on non-alcoholic fatty liver disease(NAFLD) in rat. METHODS A rat model of NAFLD was first established by feeding a high-fat diet for 14 wk. Sixty-five rats ... AIM To evaluate the hepatoprotective effect of lycopene(Ly) on non-alcoholic fatty liver disease(NAFLD) in rat. METHODS A rat model of NAFLD was first established by feeding a high-fat diet for 14 wk. Sixty-five rats were randomly divided into normal group, model group and Ly treatment groups. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglycerides(TG), total cholesterol(TC) in serum and low density lipoproteincholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), free fatty acid(FFA), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH) in liver tissue were evaluated, respectively. While the hepatoprotective effect was also confirmed by histopathological analysis, the expression levels of TNF-α and cytochrome P450(CYP) 2E1 in rat liver were determined by immunohistochemistry analysis.RESULTS A significant decrease was observed in the levels of serum AST(2.07-fold), ALT(2.95-fold), and the blood lipid TG(2.34-fold) and TC(1.66-fold) in the dose of 20 mg/kg Ly-treated rats(P < 0.01), compared to the model group. Pretreatment with 5, 10 and 20 mg/kg of Ly significantly raised the levels of antioxidant enzyme SOD in a dose-dependent manner,to 90.95 ± 9.56, 109.52 ± 11.34 and 121.25 ± 10.68(P < 0.05, P < 0.01), as compared with the model group. Similarly, the levels of GSH were significantly increased(P < 0.05, P < 0.01) after the Ly treatment. Meanwhile, pretreatment with 5, 10 and 20 mg/kg of Ly significantly reduced MDA amount by 30.87, 45.51 and 54.49% in the liver homogenates, respectively(P < 0.01). The Ly treatment group showed significantly decreased levels of lipid products LDL-C(P < 0.05, P < 0.01), improved HDL-C level and significantly decreased content of FFA, compared to the model group(P < 0.05, P < 0.01). Furthermore, the Ly-treated group also exhibited a down-regulated TNF-α and CYP2E1 expression, decreased infiltration of liver fats and reversed histopathological changes, all in a dosedependent manner(P < 0.05, P < 0.01). CONCLUSION This study suggests that Ly has a protective effect on NAFLD, down-regulates expression of TNF-α, and that CYP2E1 may be one of the action mechanisms for Ly. 展开更多
关键词 LYCOpeNe ANTIOXIDANT HepATOpROTeCTIVe Non-alcoholic fatty liver cytochrome p450 2e1
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Coexistence of hyperlipidemia and acute cerebral ischemia/reperfusion induces severe liver damage in a rat model 被引量:17
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作者 Wei-Hong Gong Wen-Xia Zheng Jun Wang Shi-Hui Chen Bo Pang Xia-Min Hu Xiao-Lu Cao 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第35期4934-4943,共10页
AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the ... AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver damage,which was confirmed by liver histology.In addition,HL combined with I/R also caused significantly increased hepatocyte apoptosis,as evidenced by increased TUNEL-positive cells(6.20 ± 0.29 vs 1.5 ± 0.22,4.47 ± 0.45 or 1.97 ± 0.47,P < 0.01),elevated expression of caspase-3 and lower expression of bcl-2.Furthermore,when compared to HL or I/R alone,HL plus I/R enhanced serum TNF-,IL-1,liver mitochondrial MDA and Ca 2+ levels,suppressed SOD and GSH-Px in liver mitochondria,and markedly up-regulated the activity(11.76 ± 2.36 vs 4.77 ± 2.31 or 3.11 ± 1.35,P < 0.01) and expression(3.24 ± 0.38 vs 1.98 ± 0.88 or 1.72 ± 0.58,P < 0.01) of CYP2E1 in liver.CONCLUSION:The coexistence of HL and acute cerebral I/R induces severe liver damage,suggesting that cerebral ischemic stroke would exaggerate the damage of liver caused by HL.This effect is possibly due to en-hanced CYP2E1 induction which further promotes oxidative damage,inflammation and hepatocyte apoptosis. 展开更多
关键词 HYpeRLIpIDeMIA High-fat diet Cerebral isch-emia/reperfusion liver damage Hepatocyte apoptosis cytochrome p450 2e1
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CYP2E1基因多态性与客家人群胃癌易感性的研究 被引量:3
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作者 李涛 赖春凤 +2 位作者 丘波 邹浩元 杨宇辉 《国际肿瘤学杂志》 CAS 2016年第7期495-498,共4页
目的:通过研究细胞色素P4502E1(CYP2E1)基因多态性位点rs2031920与客家人群胃癌遗传易感性的相关性,探讨遗传和环境因素在胃癌发病中的作用。方法采取病例-对照研究,选择经胃镜和病理检查确诊的梅州地区客家人群51例胃癌患者(胃... 目的:通过研究细胞色素P4502E1(CYP2E1)基因多态性位点rs2031920与客家人群胃癌遗传易感性的相关性,探讨遗传和环境因素在胃癌发病中的作用。方法采取病例-对照研究,选择经胃镜和病理检查确诊的梅州地区客家人群51例胃癌患者(胃癌组)和52例正常对照(对照组),对CYP2E1 rs2031920(C-1053T)位点进行基因型及等位基因检测,分析其在两组间的分布特征。结果CYP2E1 rs2031920位点在梅州地区客家人群中存在 CC、CT、TT 多态性,各基因型在胃癌组的分布频率为62.75%(32/51)、33.33%(17/51)、3.92%(2/51),在对照组的分布频率为59.62%(31/52)、34.61%(18/52)、5.77%(3/52),两组之间的差异无统计学意义(χ2=0.235,P =0.889)。CYP2E1基因rs2031920位点的等位基因 C、T 在胃癌组和对照组构成比分别为79.41%(81/102)、20.59%(21/102)和76.92%(80/104)、23.08%(24/104),差异无统计学意义(χ2=0.186,P =0.666)。经性别、年龄分层分析结果显示也无统计学意义(χ2=4.412,P =0.129;χ2=0.898,P =0.473)。结论 CYP2E1的基因多态性位点 rs2031920与客家人群胃癌的易感性不相关。 展开更多
关键词 细胞色素p450 cyp2e1 胃肿瘤 多态性 单核苷酸 客家人群 cytochrome p-450 cyp2e1
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细胞色素P4502E1基因Rsa Ⅰ/Pst Ⅰ位点多态性与中国人肺癌易感性关系的Meta分析 被引量:1
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作者 王方 杨海燕 《中华预防医学杂志》 CAS CSCD 北大核心 2010年第6期553-554,共2页
肺癌是一种由环境与遗传因素相互作用引起的多因素疾病.暴露相同的环境因素,其结局不尽相同,说明不同个体对环境致癌物具有不同的易感性.代谢酶的多态性影响个体对肺癌的易感性,有报道称细胞色素P450 2E1(CYP 2E1)基因CYP2E1 Rsa Ⅰ/P... 肺癌是一种由环境与遗传因素相互作用引起的多因素疾病.暴露相同的环境因素,其结局不尽相同,说明不同个体对环境致癌物具有不同的易感性.代谢酶的多态性影响个体对肺癌的易感性,有报道称细胞色素P450 2E1(CYP 2E1)基因CYP2E1 Rsa Ⅰ/Pst Ⅰ变异对中国人肺癌发生起保护作用,携带c1/c2或c2/c2的个体发生肺癌的危险性与c1/c1个体相比明显降低。 展开更多
关键词 细胞色素p4502e1基因 肺癌易感性 位点多态性 MeTA分析 Rsa 中国 个体发生 cyp2e1
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一氧化碳对CYP2E1介导的微粒体酒精氧化应激的保护作用
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作者 史燕如 唐玉涵 +3 位作者 高超 王迪 刘烈刚 姚平 《营养学报》 CAS CSCD 北大核心 2012年第1期28-31,共4页
目的探讨诱导I型血红素氧合酶(heme oxygenase-1,HO-1)催化血红素产生的代谢产物一氧化碳(CO)对大鼠肝微粒体细胞色素P4502E1(cytochrome P4502E1,CYP2E1)酶活性影响及其介导的酒精性氧化应激的保护作用。方法超速离心法制备大鼠肝脏微... 目的探讨诱导I型血红素氧合酶(heme oxygenase-1,HO-1)催化血红素产生的代谢产物一氧化碳(CO)对大鼠肝微粒体细胞色素P4502E1(cytochrome P4502E1,CYP2E1)酶活性影响及其介导的酒精性氧化应激的保护作用。方法超速离心法制备大鼠肝脏微粒体,加入血红素(hemin)、血红蛋白(Hb)、不同剂量的CO释放剂CORM-2(carbonmonoxide-releasing molecules-2),检测CYP2E1酶活性;在微粒体酒精氧化反应体系中加入血红素、血红蛋白及CORM-2,检测微粒体超氧化物歧化酶(SOD)活力及谷胱甘肽(GSH)、丙二醛(MDA)及氧自由基(ROS)水平。结果 hemin处理后肝微粒体CYP2E1的酶活性下降,联合Hb后CYP2E1酶活性明显升高,外源性CO则显示出类似的CYP2E1酶抑制效应;针对乙醇孵育的肝微粒体,hemin处理后明显抑制了肝微粒体MDA和ROS水平的升高,有效维持了GSH水平和SOD活力,联合Hb处理后明显抑制了上述保护效应,外源性CORM-2也显示出类似的保护效应,而灭活的CORM-2则无明显的保护效应。结论 CO对大鼠肝微粒体酒精性氧化应激具有保护作用,其机制可能与CO对CYP2E1酶活性的直接抑制有关。 展开更多
关键词 肝微粒体 I型血红素氧合酶 一氧化碳 酒精 细胞色素p4502e1(cyp2e1)
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The Physiological Mechanism of Improved Formaldehyde Resistance in Petunia hybrida Harboring a Mammalian cyp2e1 Gene 被引量:2
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作者 WANG Man XIANG Taihe +3 位作者 SONG Yaling HUANG Yingying HAN Yixuan SUN Yang 《Horticultural Plant Journal》 SCIE 2015年第1期48-54,共7页
Cytochrome P450 CYP2E1 is mainly present in hepatocytes in the livers of mammals,where it plays an important role in the metabolism of xenobiotic organic substances. Previous studies showed that transgenic petunia(Pet... Cytochrome P450 CYP2E1 is mainly present in hepatocytes in the livers of mammals,where it plays an important role in the metabolism of xenobiotic organic substances. Previous studies showed that transgenic petunia(Petunia hybrid) plants harboring a mammalian cyp2e1 gene(designated cyp2e1-transgenic petunia) exhibited increased resistance to formaldehyde stress. In this study,we used cyp2e1-transgenic petunia plants to analyze physiological indexes related to formaldehyde stress responses. The results indicated that under formaldehyde stress,the malondialdehyde content in cyp2e1-transgenic petunia plants was lower than in β-glucuronidase gene(gus)-transgenic and wild-type petunia plants. The activities of both superoxide dismutase and peroxidase in the cyp2e1-transgenic plants were higher than in gus-transgenic and wild-type plants. The alcohol dehydrogenase activity was slightly increased and more glutathione was consumed. Additionally,under formaldehyde stress,the levels of plant hormones including indole-3-acetic acid,zeatin and abscisic acid in cyp2e1-transgenic petunia plants displayed decreasing trends,whereas the level of gibberellic acid displayed an increasing trend. In contrast,the indole-3-acetic acid,zeatin and abscisic acid levels in gus-transgenic and wild-type petunia plants displayed increasing trends,whereas the gibberellic acid level displayed a decreasing trend. At 72 h after incubation of 0.5 g of cyp2e1-transgenic petunia plants in 40 mL of treatment solution containing formaldehyde at 50 mg·L^(-1),the formaldehyde content remaining in the treatment solution was close to zero while approximately half of original formaldehyde remained in the treatment solutions containing gus-transgenic and wild-type petunia plants. 展开更多
关键词 petunia hybrida cytochrome p450 cyp2e1 formaldehyde stress transgenic plant
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Hepatocellular carcinoma in alcoholic liver disease: mechanistic considerations and clinical facts 被引量:1
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作者 Rolf Teschke 《Hepatoma Research》 2019年第11期1-16,共16页
Alcoholic hepatocellular carcinoma(AHCC)represents a lethal stage,emerging in the course of severe injurious stages of alcoholic liver disease including cirrhosis.AHCC only affects a few alcohol consumers,certainly no... Alcoholic hepatocellular carcinoma(AHCC)represents a lethal stage,emerging in the course of severe injurious stages of alcoholic liver disease including cirrhosis.AHCC only affects a few alcohol consumers,certainly not all individuals who consume large amounts of alcohol over a long period of time,suggesting a role of yet unknown genetic risk or protection factors.Most likely,hepatic DNA is ultimately involved,attacked by intermediate products derived from reactive oxygen species(ROS)generated from cytochrome P4502E1 of the NADPH and oxygen dependent microsomal ethanol-oxidizing system whereby ethanol is metabolized.Ethanol and acetaldehyde are activated to procarcinogens,to be promoted to ultimate carcinogens by ROS and causatives for AHCC instead of any other putative chemical contained in alcoholic beverages.Prevention of HCC associated with cirrhosis is best accomplished by early recognition of alcohol abuse at the stage of alcoholic fatty liver rather than alcoholic hepatitis(AH)or alcoholic steatohepatitis(ASH),leading to the advice of consequent abstinence from alcohol.Abstinence early started effectively prevents AHCC development,as opposed to late begin of abstinence that lacks risk reduction.Although drug therapy may partially be effective in AH or ASH,no established drug options are available for a realistic therapy of AHCC.Liver transplantation is controversially discussed and can be considered,but may be an option for only a few patients on a case by case base.In conclusion,AHCC results from a ROS dependent conversion of ethanol and acetaldehyde to procarcinogens as promoters of AHCC. 展开更多
关键词 Alcohol alcoholic liver disease alcoholic cirrhosis alcoholic hepatocellular carcinoma microsomal ethanol-oxidizing system cytochrome p4502e1 reactive oxygen species CARCINOGeNS
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胆宁片防治非酒精性脂肪肝的实验研究 被引量:13
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作者 陈鹏 顾勤 +1 位作者 周晓波 杨洪宝 《吉林中医药》 2014年第4期399-402,共4页
目的研究胆宁片对大兔脂肪肝的防治作用。方法采用高胆固醇膳食致兔脂肪肝模型,研究胆宁片对大兔非酒精性脂肪肝的防治作用。结果模型组与胆宁片组的TC数值分别为(15.36±9.01)mg/dL、(2.67±5.35)mg/dL,TG分别为(1.11±0.4... 目的研究胆宁片对大兔脂肪肝的防治作用。方法采用高胆固醇膳食致兔脂肪肝模型,研究胆宁片对大兔非酒精性脂肪肝的防治作用。结果模型组与胆宁片组的TC数值分别为(15.36±9.01)mg/dL、(2.67±5.35)mg/dL,TG分别为(1.11±0.42)mmol/L、(0.56±0.2)mmol/L,LDL-C分别为(13.16±7.39)mmol/L、(1.98+5.00)mmol/L,HDL-C分别为(0.49±0.23)mmol/L、(0.90±0.29)mmol/L,2组数据相比较,差异有显著性统计学意义(P<0.01),模型组新西兰兔的肝脏组织CYP7A1 mRNA表达较胆宁片组低,其中模型组与胆宁片组条带值分别为(0.56±0.14)(1.02±0.09),差异有统计学意义(P<0.001)。而模型组CYP2E1 mRNA表达较胆宁片组高,其中模型组与胆宁片组条带值分别为(1.49±0.31)(1.22±0.20),差异有统计学意义(P<0.05)。结论胆宁片对实验性大兔脂肪肝有一定的治疗作用。 展开更多
关键词 胆宁片 非酒精性脂肪肝 胆固醇7α-羟化酶(cyp7A1) 肝脏细胞色素酶p4502e1(cyp2e1) 大兔 抗氧化
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连翘提取物对对乙酰氨基酚诱导小鼠肝损伤的保护作用 被引量:6
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作者 赵晨栋 王萌 +4 位作者 张昊 代国年 安志霞 沈雅丽 王桂荣 《中国畜牧兽医》 CAS 北大核心 2021年第10期3845-3854,共10页
试验旨在探究连翘提取物(FSE)预防性干预对对乙酰氨基酚(acetaminophen,APAP)诱导小鼠肝损伤的保护作用及其潜在作用机制。采用半仿生-生物酶法提取连翘有效成分,使用APAP构建小鼠肝损伤模型。随机将60只雌性昆明小鼠分入正常对照(NC)组... 试验旨在探究连翘提取物(FSE)预防性干预对对乙酰氨基酚(acetaminophen,APAP)诱导小鼠肝损伤的保护作用及其潜在作用机制。采用半仿生-生物酶法提取连翘有效成分,使用APAP构建小鼠肝损伤模型。随机将60只雌性昆明小鼠分入正常对照(NC)组、APAP肝损伤模型(LD)组、连翘提取物(FSE)对照组、连翘提取物高剂量(HFSE+LD)组、连翘提取物中剂量(MFSE+LD)组和连翘提取物低剂量(LFSE+LD)组,每组10只。HFSE+LD组、MFSE+LD组、LFSE+LD组分别按每天200、100、50μg/g灌胃给予连翘提取物,NC组和LD组分别灌胃等量生理盐水,每天2次,连续给药6 d。预防性给药3 d后,腹腔注射APAP,每天1次。末次给药12 h后,试验小鼠眼球采血并快速取出肝脏,检测血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)活性,以评价肝损伤程度;检测肝脏匀浆液中还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、丙二醛(MDA)和过氧化氢(H2O2)水平,以评价肝脏氧化应激程度;制作肝脏病理切片,经苏木精伊红(HE)染色后观察肝脏病理变化;采用探针药物法测定肝脏线粒体细胞色素P4502E1(CYP2E1)活性;采用实时荧光定量PCR检测肝脏线粒体CYP2E1 mRNA表达水平;采用Western blotting法检测肝脏CYP2E1蛋白表达情况。结果表明:与NC组相比,LD组小鼠血清中ALT、AST活性均显著增加(P<0.05);肝脏SOD活性、GSH含量均显著降低(P<0.05),MDA、H2O2含量,CYP2E1 mRNA及蛋白表达水平均显著升高(P<0.05),成功构建小鼠肝损伤模型。200、100和50μg/g的连翘提取物可显著降低肝损伤小鼠血清ALT和AST活性(P<0.05),显著提高肝脏中SOD活性(P<0.05);200、100μg/g连翘提取物可显著提高肝脏中GSH水平(P<0.05),显著降低肝脏中MDA、H2O2水平及CYP2E1的mRNA和蛋白表达量(P<0.05)。以上结果表明,连翘提取物可减轻APAP诱导的小鼠肝损伤程度且呈剂量依赖性,其潜在作用机制可能与所含活性物质的抗氧化作用以及对CYP2E1酶活性和表达的抑制有关。 展开更多
关键词 连翘提取物 对乙酰氨基酚 细胞色素p4502e1(cyp2e1) 肝损伤
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