丙戊酸钠对急性髓系白血病细胞株HL-60增殖和凋亡的影响

目的研究丙戊酸钠（VPA）对急性髓系白血病细胞株HL-60细胞的增殖抑制及诱导凋亡作用,探讨其可能作用机制。方法采用CCK-8法检测细胞生长抑制率;经瑞氏-姬姆萨（Wright—Giemsa）染色,光镜下观察经VPA处理后细胞的形态学改变;应用流式细胞仪检测细细胞周期和细胞凋亡率。结果VPA对HL-60细胞的增殖抑制作用呈时间和浓度依赖性。经2．0mmol／LVPA处理HL-60细胞48h后,显微镜下可见凋亡细胞胞体固缩、核固缩、核碎裂及凋亡小体。经1．0和2．0mmol／LVPA处理HL-160细胞48h后,流式细胞仪检查结果表明细胞凋亡率由处理前的（1．25±0．457）％分别上升为（3．27±0．984）％和（10．3±3．4）％,差并有统计学意义（P〈O．05）;G0／G1期细胞比例逐渐上升,S期细胞比例及细胞增殖指数（PI）呈下降趋势,细胞被阻滞在G0／G1期（P〈0．01）。结论VPA对HL-60细胞具有增殖抑制和诱导细胞凋亡作用。且呈剂量一时间依赖性;作用机制与细胞周期阻滞有关。     

细胞色素P4502E1基因RsaI／PstI位点多态性与中国人食管癌发病风险关系的Meta分析

目的通过Meta分析的方法系统评价细胞色素P45a2El（CYP2EI）基凶RsaI／PsiI位点多态性与中国人食管癌发病风险的相关性。方法检索PubMed、Embase、CBM,CNKI、VIP和WANFANG数据库中1990年1月1日至2011年11月30日有关CYP2E1基冈多态性与食管癌发病风险关系的文献,进行文献筛选、质量评：价和数据提取后,采用RevMan5．1软件进行Meta分析。结果最终纳入18篇病例对照研究共19个试验,其中食管癌患者1663例,对照2603例。Meta分析结果显示CYP2E1基因多态性与食管癌的关联有统计学意义[c2vs．c1：OR=0．64,95％Cl=0.50—0．81,JP=O．0003;c2／c2vs．c1／c1：OR=0．70,95％CI=0．56—0．89,P=0。003;c1／c2vs．c1／c1：OR=0．54,95％C,=0．38—0．75,P=0．0003;c2／c2vs,（c1／c1＋c1／c2）：OR=0．73,95％CI=0．58—0．92,P=0．008;（c1／c2＋c2／c2）vs．c1／c1：OR=0．48,95％vs：0．34—0．70,P=0．0001];汉族的亚组分析结果也显示cYP2E1基因多态性与食管癌的关联有统计学意义[c2vs．c1：OR=O．71,95％CI=0．57—0．89,P=0．002;c2／c2vs．c1／c1：OR=0．75,95％CI=0．59—0．95,P=0．02;c1／c2vs．c1／c1：OR=0．62,95％（1,=0．46—0．84。P=0．002;c2／c2vs．（c1／c1＋c1／c2）：OR=0．78,95％CI=0．61～0．99,P=0．04;（c1／c2＋c2／c2）vs．c1／c1：OR=O．56,95％CI=0．40—0.79,P=0．001]。结论对目前相关研究结果的Meta分析佩示CYP2EI基凶多态性与中国人群食管癌发生风险具有相关性,其RsaI／PstI位点的e2等位基阒可能是食管癌的保护或抑制冈素。     

Associations of genetic polymorphisms of the vitamin D pathway with blood pressure in a Han Chinese population

Vitamin D deficiency can lead to high blood pressure. Polymorphisms in the vitamin D hydroxylase gene have been associated with serum vitamin D levels in some Western countries. The aim of this study was to investigate whether polymorphisms of hydroxylase genes in the vitamin D metabolic pathway contribute to hypertension by affecting serum vitamin D status in a Han Chinese population. We selected four single nucleotide polymorphisms (SNPs; rs1993116 and rs10741657 of CYP2R1; rs4809957 and rs6068816 of CYP24A1) for genotyping in 525 control subjects and 324 hypertensive patients, and detected vitamin D levels in blood in subsets of these groups. The results showed that rs1993116 and rs10741657 were associated with a reduced risk of hypertension. The odds ratios, 95% confidence intervals, and p values from the adjusted additive and dominant models were 0.788 (0.644–0.963, p = 0.02) and 0.719 (0.545–0.949, p = 0.02) for rs1993116 and 0.805 (0.66–0.983, p = 0.033) and 0.733 (0.556–0.966, p = 0.028) for rs10741657. A protective effect of CYP2R1 with regard to hypertension was also found in males and non-smokers. The TT genotypes of rs1993116 and rs10741657 were associated with significantly lower systolic blood pressure in treated hypertensive patients (both p = 0.002). No association with hypertension was found for the two SNPs of CYP24A1, and no difference in vitamin D level was found among the three genotypes of the four SNPs. Our results suggest that CYP2R1 polymorphisms are associated with a reduced risk of hypertension independent of the vitamin D level in the Han Chinese population.     

Microsomal Ethanol‐Oxidizing System: Success Over 50 Years and an Encouraging Future

Fifty years ago, in 1968, the pioneering scientists Charles S. Lieber and Leonore M. DeCarli discovered the capacity for liver microsomes to oxidize ethanol (EtOH) and named it the microsomal ethanol‐oxidizing system (MEOS), which revolutionized clinical and experimental alcohol research. The last 50 years of MEOS are now reviewed and highlighted. Since its discovery and as outlined in a plethora of studies, significant insight was gained regarding the fascinating nature of MEOS: (i) MEOS is distinct from alcohol dehydrogenase and catalase, representing a multienzyme complex with cytochrome P450 (CYP) and its preferred isoenzyme CYP 2E1, NADPH–cytochrome P450 reductase, and phospholipids; (ii) it plays a significant role in alcohol metabolism at high alcohol concentrations and after induction due to prolonged alcohol use; (iii) hydroxyl radicals and superoxide radicals promote microsomal EtOH oxidation, assisted by phospholipid peroxides; (iv) new aspects focus on microsomal oxidative stress through generation of reactive oxygen species (ROS), with intermediates such as hydroxyethyl radical, ethoxy radical, acetyl radical, singlet radical, hydroxyl radical, alkoxyl radical, and peroxyl radical; (v) triggered by CYP 2E1, ROS are involved in the initiation and perpetuation of alcoholic liver injury, consequently shifting the previous nutrition‐based concept to a clear molecular‐based disease; (vi) intestinal CYP 2E1 induction and ROS are involved in endotoxemia, leaky gut, and intestinal microbiome modifications, together with hepatic CYP 2E1 and liver injury; (vii) circulating blood CYP 2E1 exosomes may be of diagnostic value; (viii) circadian rhythms provide high MEOS activities associated with significant alcohol metabolism and potential toxicity risks as a largely neglected topic; and (ix) a variety of genetic animal models are useful and have been applied elucidating mechanistic aspects of MEOS. In essence, MEOS along with its CYP 2E1 component currently explains several mechanistic steps leading to alcoholic liver injury and has a promising future in alcohol research.     

环氧二十碳三烯酸与老年糖尿病血管内皮舒张功能障碍的相关性

目的比较观察老年糖尿病(DM)、老年糖尿病肾病(DN)和健康老年人之间血清14,15-环氧二十碳三烯酸(14,15-EET)的代谢产物14,15-双羟二十碳三烯酸(14,15-DHET)的含量变化,并分析与血管内皮舒张功能障碍的相关性。方法 196例志愿者和患者分为3组:健康老年人组(A组)60例、老年DM组(B组)78例和老年DN组(C组)58例,每组男、女匹配。应用酶联法检测3组血清中14,15-DHET、前列环素(PGI2)代谢产物6-keto-PGF1α和血栓素TXA2代谢产物TXB2的含量,同时检测血糖、血脂等生化指标。采用彩色多普勒超声仪对肱动脉基础内径、血管内皮依赖性舒张功能(EDV)和硝酸甘油介导的血管内皮非依赖性舒张功能(NEDV)进行测定。结果 B组和C组分别与A组比较:(1)血清14,15-DHET和6-keto-PGF1α含量下降(P<0.01),TXB2含量升高(P<0.01);(2)TXB2/6-keto-PGF1α比值和TXB2/14,15-DHET比值升高(P<0.01);(3)糖化血红蛋白(HbA1c)、三酰甘油(TG)和总胆固醇(TC)、尿白蛋白排泄量(UAE)均升高(P<0.01);(4)EDV和NEDV降低(P<0.01)。(5)14,15-DHET含量与DM病程、HbA1c、UAE、TXB2、TXB2/6-keto-PGF1α比值和TXB2/14,15-DHET比值负相关,与EDV和NEDV正相关。结论老年DM和老年DN患者血清中血管内皮依赖性的舒血管因子代谢产物14,15-DHET含量下降发生在DM早期阶段。与PGI2一样,14,15-DHET含量变化可作为判断DM、DN相关的血管EDV和NEDV功能受损的重要指标之一。     

CYP2C9和VKORC1基因多态性对华法林剂量的影响

华法林是临床上广泛使用的口服抗凝药物,其治疗范围窄,个体差异大,尤其在治疗初期,易导致严重的出血并发症,如何合理、安全使用成为国内外研究者关注的重点和难点。华法林的疗效受多种因素的影响,以遗传因素中基因多态性较为突出。近年来,随着药物基因组学的快速发展,研究发现药动学和药效学多个相关基因的多态性造成了华法林的个体差异。现从基因多态性角度综述CYP2C9和VKORC1基因的遗传变异对华法林药物反应差异的影响。     

食品动物细胞色素P450的研究进展

细胞色素P450酶系是参与药物及各种内源性和外源性化合物在体内的主要代谢酶,目前研究猪、牛、羊、鸡和鱼等食品动物的细胞色素P450代谢酶越来越受到重视。研究食品动物细胞色素P450,对明确其代谢转化机制、指导兽医临床合理用药、新兽药设计与剂型改进、预防兽药相互作用、种属外推用药、食品动物兽药残留消除分析及人类食品安全评价,都具有十分重要的意义。     

肝再生增强因子,细胞色素P450与人肝癌细胞在体外耐药的关系

目的:研究肝癌顺铂耐药细胞HepG2/cDDP中人肝再生增强因子(Human augmenter of liver regeneration,hALR)对细胞色素P450(Cytochrome P450,CYP450)表达的影响,观察ALR是否通过作用CYP450与肝癌细胞耐药的形成有关.方法:建立体外肝癌顺铂耐药细胞...