The role of polymorphic cytochrome P450 gene(CYP2B6)in B-chronic lymphocytic leukemia(B-CLL)incidence and outcome among Egyptian patients

Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used drugs.This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide chemotherapy.DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy individuals.The presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed up.The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT vs.GG,OR=5.4,p<0.001)models.Following cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian patients.This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1

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.

酒精性肝损伤大鼠细胞色素P450 CYP2E1和细胞色素P450 CYP3A的代谢活性

目的观察酒精性肝损伤对大鼠细胞色素P450CYP3A(CYP3A)和细胞色素P450CYP2E1(CYP2E1)代谢活性的影响。方法采用ig给予白酒制备大鼠酒精性肝损伤模型,检测血清中谷丙转氨酶(GPT)和谷草转氨酶(GOT)活性,采用HE染色法光镜下观测酒精对肝脏损伤程度。大鼠ip给予CYP3A探针药物咪达唑仑10mg·kg-1或ig给予CYP2E1探针药物氯唑沙宗50mg·kg-1后,采用高效液相色谱法测定不同时间点大鼠血浆中咪达唑仑和氯唑沙宗的血药浓度,并应用3P87软件计算其药代动力学参数,以考察CYP2E1和CYP3A的代谢活性的变化。大鼠ig给予氯唑沙宗80mg·kg-1后,热板方法测定大鼠添足次数和添足反射潜伏期。结果酒精性肝损伤可致大鼠肝小叶结构不清,肝索排列紊乱,肝细胞体积增大,呈弥漫性中度水变性,肝窦受压,大部分肝细胞胞浆内见大小不等的脂肪空泡;与正常对照组相比,酒精性肝损伤组大鼠GPT和GOT活性分别增加了16.0%和20.0%(P<0.05,P<0.01)。酒精性肝损伤致大鼠CYP2E1对探针药物氯唑沙宗的代谢活性增强,AUC,t1/2和cmax分别降低了38.0%,30.5%和35.0%(P<0.05);酒精肝损伤组大鼠氯唑沙宗镇痛效果明显降低;酒精性肝损伤致大鼠CYP3A对探针药物咪达唑仑的代谢活性增强,AUC,t1/2和cmax分别降低了122.6%,54.9%和56.9%(P<0.01,P<0.05)。结论酒精性肝损伤可使大鼠CYP2E1和CYP3A代谢活性增强。

淡色库蚊细胞色素P450 CYP4E2r6基因的克隆、表达及鉴定

目的克隆并表达鉴定淡色库蚊细胞色素P450(CYP4E2r6)基因。方法根据昆虫细胞色素P450氨基酸保守序列设计一对简并引物,采用RT-PCR,从淡色库蚊四龄幼虫mRNA中扩增出目的基因片段。产物经T-A克隆、测序、比对,在抗性品系高表达的CYP4E2r6亚克隆入原核表达载体pGEX-6P1,在大肠杆菌BL21中进行原核表达,将细菌总蛋白进行SDS-PAGE及Westernblot鉴定。结果14个阳性克隆中9个为CYP4新序列,由GenBank登录上网(GenBank/NCBICB074944-51、CB270837,2003年);经鉴定属CYP4家族CYP4H、CYP4E、CYP4J亚家族;CYP4E2r6基因已成功表达。结论获得的CYP4E2r6融合表达蛋白为进一步研究CYP4基因与抗药性之间的关系奠定基础。

细胞色素P450 CYP2E1酶构型特征及其表达调控机制的研究进展

细胞色素P450CYP2E1酶参与代谢活化及失活多种前毒物、前致癌物和少数药物。在细胞色素P450超家族中,CYP2E1具有易介导自由基生成引发氧化应激反应的特征。CYP2E1表达水平可能是机体对环境和工业毒物或致癌物敏感程度的重要因素。研究表明,CYP2E1可被多种内、外源性物质所调控,并且CYP2E1的药理和毒理学功能与其以蛋白构型为基础的代谢行为密切相关。本文综述了CYP2E1基因多态性、酶构型特征与其代谢活性间的关系,并分析了其区别于其他细胞色素P450亚型的表达调控机制。

3Gyγ射线照射和丝裂霉素C对大鼠肝脏细胞色素P450含量及其同工酶CYP2B1、CYP2E1活性的影响

为研究3Gyγ射线全身照射和丝裂霉素C(MitomycinC,MMC)对雄性(Sprague-Dawley,SD)大鼠肝脏细胞色素P450含量、CYP2B1、CYP2E1活性的影响,分别给大鼠腹腔注射1mg/kgd的MMC(分1d,连续3d及6d用药三组),3mg/kg的MMC1d,3Gyγ射线全身照射,3Gyγ射线全身照射加1d3mg/kgMMC,另设空白对照和溶剂对照。各组处理结束后24h,处死大鼠取肝脏,制备微粒体,测P450含量、CYP2B1、CYP2E1活性。实验结果表明,给MMC1mg/kgd,1d后P450含量、CYP2B1活性变化无统计学差异(p>0.05),CYP2E1活性明显上升(p<0.01);连续3d或6d后,P450含量、CYP2B1、CYP2E1活性均无明显变化(p>0.05)。给3mg/kg的MMC1d,对P450含量、CYP2B1活性影响无统计学差异(p>0.05),CYP2E1活性上升明显(p<0.01);3Gyγ射线全身照射后,P450含量、CYP2B1活性无明显变化(p>0.05),CYP2E1活性下降(p<0.05);分析发现,3mg/kgMMC与3Gyγ射线之间没有交互作用。结果提示,γ射线可以抑制雄性SD大鼠肝脏CYP2E1活性,MMC对CYP2E1活性有诱导作用,但多次刺激使其耐受,P450含量、CYP2B1活性对γ射线、MMC不敏感。

ASA法测定细胞色素P4502D6酶缺陷等位基因CYP2D6E

目的 :建立细胞色素P4 50 2D6(CYP2D6)第 3 0 2 3位A→C突变造成CYP2D6酶活性缺陷的等位基因CYP2D6E的测定方法。方法 :利用等位基因特异扩增法 (ASA)为基本原理 ,设计两对引物分别扩增野生型等位基因和突变型等位基因。结果 :经 3 96例测定 ,发现 2例CYP2D6E与CYP2D6B的异突变型纯合子 ,其表现型均为慢代谢者。阳性对照说明本法重复性好 ,阴性对照显示本法无污染问题。结论 :本法比PCR -RFLP法更为快捷、更少污染。

来氟米特对急性化学性肝损伤小鼠肝Cyt.P450酶含量及CYP2E1 mRNA表达的影响

目的观察来氟米特(Lef)作用前后急性化学性肝损伤小鼠肝微粒体细胞色素P450(Cyt.P450)、细胞色素b5(Cyt.b5)含量及P4502E1(CYP2E1)mRNA表达水平的变化,进一步研究其治疗机制。方法采用CCl4诱导小鼠急性化学性肝损伤模型,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性,肝匀浆丙二醛(MDA)、谷胱甘肽(GSH)含量以及肝微粒体细胞色素P450(Cyt.P450)和细胞色素b5(Cyt.b5)含量,RT-PCR法检测小鼠肝脏细胞色素P4502E1(CYP2E1)mRNA表达水平,并作肝组织切片病理观察。结果Lef明显降低CCl4急性肝损伤小鼠血清ALT、AST水平;降低肝匀浆MDA含量;提高GSH含量并提高肝微粒体Cyt.P450、Cyt.b5含量;抑制CYP2E1 mRNA表达;减轻肝脏病理损伤。结论Lef治疗CCl4所致小鼠急性化学性肝损伤,可能与其诱导肝微粒体Cyt.P450表达,抑制CYP2E1 mRNA转录及抗脂质过氧化有关。

Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle,Fujian Province

AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 ( CYP2 E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitroscoamines and Iow molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2Elpolymorphisms are associated with risk s of gastric cancer.METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including dsmographic characteristcs, diet intake, and alcohol and tobacco consumption of indivduals in our study were completed by a standardized questionnaire. PCR-RFLP revealed three genotypes: heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1.RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 indivduals in gastric cancer group(6.6%),whereas there was only one in the control group (1.1%).However, there was no statistically significan difference between the two groups (two-tailed Fisher′s exact test, P =0.066). Indivduals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR = 1.50) and C2/C2(OR = 7.34) than indivduals in control group (X2 = 4.597, for trend P=0.032). The frequencies of genofypes with the C2allele ( C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele ( C1/C1 genotype )among indivduals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that indivduals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer.CONCLUSION: Polymorphism of CYP2E1 gene may have some effct in the development of gastric cancer in Changle county, Fujian Province.

Hepatoprotective effects of S-adenosyl-L-methionine against alcohol-and cytochrome P450 2E1-induced liver injury

S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic SAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection.

Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significanly correlated with cytochrome P450 suppression

AIM:To investigate the hepatoprotective activity of tea polyphenols(TP)and its relation with cytochrome P450(CYP450)expression in mice. METHODS:Hepatic CYP450 and CYPb5 levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP(25,50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100,200 and 400 mg/kg per day)for six days before paracetamol(1000 mg/kg)was given.Their acute mortality was compared with that of control mice. The mice were pre-treated with TP(100,200,and 400 mg/kg per day)for five days before paracetamol (500 mg/kg)was given.Hepatic CYP2E1 and CYP1A2 protein and mRNA expression levels were evaluated by Western blotting,immunohistochemical staining and transcriptase-polymerase chain reaction. RESULTS:The hepatic CYP450 and CYPb5 levels in mice of TP-treated groups(100,200 and 400 mg/kg per day)were decreased in a dose-dependent manner compared with those in the negative control mice.TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice.Furthermore,TP reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner.

Cytochrome P450 2E1 RsaI/PstI and DraI Polymorphisms Are Risk Factors for Lung Cancer in Mongolian and Han Population in Inner Mongolia

Objective： To explore the relationship between cytochrome P450 2E1 （CYP2E1） RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods： CYP2E1 RsaI/PstI and DraI polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 64 lung cancer patients, 150 healthy Mongolian and 150 healthy Han individuals. The distribution of genotype and allele frequencies of CYP2E1 RsaI/PstI and DraI polymorphisms were studied. Results： The risk of lung cancer was increased in individuals with CYP2E1 （cl/cl） and CYP2E1 （DD） with OR values of 2.431 （95%CI=1.082-5.460） and 2.778 （95%CI=1.358-5.683） respectively （P0.05）. When CYP2E1 RsaI/PstI and DraI polymorphisms were combined, the risk of lung cancer was reduced in individuals with CYP2E1 （cl/c2＋c2/c2 and DD＋CC） with OR values of 0.233 （95%CI=0.088-0.615, P0.05）. In smokers, the susceptibility to lung cancer was higher in the individuals with CYP2E1 （c1/c1） and CYP2E1 （DD） than in the individuals with c2 and C allele （P0.05, OR=2.643 and 4.308 respectively）. There was no significant difference in distribution of CYP2E1 genotype frequency between healthy Mongolian, Han population and lung cancer patients, healthy controls in Inner Mongolia. Conclusion： CYP2E1 （c1/c1） and CYP2E1 （DD） are predisposing factors of lung cancer in population in Inner Mongolia. CYP2E1 （c2﹢C） co-mutation may decrease the risk of lung cancer. Smoking exerts synergetic effect with CYP2E1 （c1/c1） and CYP2E1 （DD） on the occurrence of lung cancer.

柴胡水提液对大鼠肝CYP450酶含量及其亚型CYP3A、CYP2E1和CYP1A2活性的影响

目的:研究柴胡水提物对大鼠细胞色素CYP450酶含量及对亚型CYP3A、CYP2E1和CYP1A2活性的影响。方法:大鼠灌胃给予柴胡水提液7d后取肝脏称重并制备肝微粒体,紫外分光光度法测定肝微粒体细胞色素b5(Cytb5)、P450的含量及CYP3A的活性,高效液相法测定CYP2E1和CYP1A2的活性。结果:与空白对照组比较,柴胡水提液组大鼠肝指数无显著变化,CYP450含量减少但统计学意义(P>0.05),CYP1A2活性极显著降低(P<0.01),CYP2E1活性明显降低(P<0.05)。结论:柴胡水提液降低大鼠肝脏CYP450酶含量并抑制CYP2E1和CYP1A2的活性,由于抑制CYP450酶活性,减少对其他药代谢,提示若柴胡水提液与经CYP2E1和CYP1A2代谢的药物同用,有可能会影响这些药物的临床疗效,临床用药时应慎重考虑。

In vitro and in vivo cytochrome P450 3A enzyme inhibition by Aframomum melengueta and Dennettia tripetala extracts

Objective: To evaluate the in vitro and in vivo inhibitory effects of two commonly used herbs, Aframomum melengueta(A. melengueta) and Dennettia tripetala(D. tripetala) on CYP 3A enzymes. Methods: In vitro inhibition of the enzymes were assessed with microsomes extracted from female albino rats using erythromycin-N-demethylation assay(EMND) method while their in vivo effects were measured by estimating simvastatin plasma concentrations in rats. Pharmacokinetic parameters were determined using non-compartmental anaysis as implemented in Win Nonlin pharmacokinetic program. Results: EMND assay with intestinal microsomes indicated that aqueous extracts of D. tripetala and A. melengueta significantly(P < 0.05) inhibited intestinal CYP 3A activity at both 50 μg and 100 μg concentrations. Petroleum ether extract of D. tripetala and ethanol extracts of A. melengueta inhibited intestinal CYP3 A activity at 100 μg but not at 50 μg concentrations. All the extracts showed an in vitrodose dependent CYP 3A inhibition with liver microsomes. In vivo analysis showed that pretreatment with the extracts enhanced systemic absorption of simvastatin with reductions in metabolizing enzymes activity as indicated in significant increases in maximal concentration, area under curve, area under moment curve and mean resident time of simvastatin(P < 0.05). Conclusions: Herbal preparations containing these plants' extracts should be used with caution especially in patients on CYP450 3A substrate medications.

Identification and analysis of a processed cytochrome P450 pseudogene of the disease vector Aedes aegypti

Objective: To clone cytochrome P450 from Aedes aegypti(Ae. aegypti) and determine the characteristics using bioinformatics tools. Methods: Cytochrome P450 of Ae. aegypti was amplified using polymerase chain reaction, cloned and sequenced. Evolutionary relationship of the sequence was inferred and bioinformatics tools were used to predict subcellular localisation, signal peptide, transmembrane helix, phosphorylation, O-glycosylation, secondary and tertiary structures of the deduced protein. Results: Polymerase chain reaction rather amplified a cytochrome P450 pseudogene which was named CYP4H44P(Gen Bank accession number KF779932). The pseudogene has 1537 nucleotides and an open reading frame of 335 amino acids containing cytochrome P450 motifs except the Wxxx R motif. It is highly homologous to CYP4H28 and CYP4H28v2. Phylogenetic analysis and evolutionary divergence showed strong clustering with CYP4H28 alleles and least divergence from the alleles respectively. The deduced protein was predicted to be found in the cytoplasm and likely to be phosphorylated but devoid of signal peptide, transmembrane helix and O-glycosylated sites. The secondary and tertiary structures were also generated. Conclusions: A cytochrome P450 pseudogene, CYP4H44 P was cloned from Ae. aegypti. The pseudogene is homologous with CYP4H28 alleles and seems to have recently diverged from this group. Isolating this pseudogene is an important step for evaluating its biological role in the mosquito and for the evolutionary analysis of Ae. aegypti CYPs.

Expression of cytochrome P450 2A13 in human non-small cell lung cancer and its clinical significance

Lung cancer is one of the most important causes of cancer-related mortality worldwide. Human cytochrome P450 2A13 enzyme （CYP2A13） is predominantly expressed in the respiratory tract and could catalyze various carcinogens. In this study, we quantified CYP2A13 expression in non-small cell lung cancer （NSCLC） tissues and examined the relation between CYP2A13 and clinicopathologic factors. Thirty-five paired lung cancer and normal tissues were studied for the expression of the CYP2A13 gene by using real-time PCR and Western blot- ting assays. We also investigated the relationship between CYP2A13 expression and clinicopathologic factors such as age, gender, histology and lymph node status in tumor tissues. SPSS （17.0） statistical software was applied for data analysis. The real-time PCR results showed that there was no significant difference in the CYP2A13 mRNA transcript levels between tumor and paired normal tissues in the 35 samples and in 12 paired squamous cell car- cinomas. In adenocarcinoma, the expression of CYP2A13 mRNA in tumor tissues was 12.5% of that in adjacent tissues （P 〈 0.05） and it was not associated with age, gender, histology and lymph node status of the patients. The amounts of CYP2A13 proteins detected by Western blotting assays correlated well with those of the correspond- ing mRNAs. In conclusion, the expression of CYP2A13 was downregulated in lung adenocarcinoma. CYP2A13 may be involved in the development and progression of lung adenocarcinoma.

细胞色素P450(CYP450)遗传多态性研究进展

近年来对CYP450基因型和表型相关性的研究越来越受到重视,从临床合理用药方面来说,人们希望利用基因型分析来了解个体中药物代谢酶的活性,期望既能提高药物治疗水平同时又降低不良反应的发生;从新药研发角度来说,研究药物的代谢酶CYP450的功能能够指导新药的设计、筛选及优化。该文通过查阅国内外相关文献综述了近年来关于CYP450遗传多态性研究的进展,分别介绍了CYP2C19、CYP2C9、CYP3A4、CYP2D6、CYP1A2和CYP2E1这6种主要的药物代谢酶。研究CYP450对新药设计、筛选、评价及优化有重要意义。

细胞色素 P450 2E1 的研究进展

ＣＹＰ２Ｅ１在药物和人们经常接触的溶剂与环境污染物的代谢中具有重要作用。本文综述ＣＹＰ２Ｅ１的结构特点、基因、底物和探药以及影响其活性的主要因素。

CYP1A1、CYP2E1基因多态性与癌症易感性的研究进展

人类细胞色素P450(CYP450)在多种内源性及外源性物质的生物代谢中起重要作用。大多数CYP450存在基因多态性,其中CYP1A1、CYP2E1两个基因多态性与癌症的发生密切相关。本文综述了近年来人类细胞色素P4501A1(CYP1A1)和P4502E1(CYP2E1)与癌症易感性之间关系的研究进展。

二斑叶螨不同抗性品系最佳内参基因的筛选及CYP392E亚家族基因的表达分析

【目的】筛选二斑叶螨Tetranychus urticae敏感品系(SS)、抗阿维菌素品系(Av-R)和抗螺虫乙酯品系(Sp-R)中合适的内参基因,研究二斑叶螨不同抗性品系CYP392E亚家族基因表达水平的变化。【方法】采用实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)技术,对二斑叶螨α-tubulin,β-actin,ELFn,GAPDH,5.8S rRNA基因和SDHA共6个看家基因的表达稳定性进行分析以期筛选出合适的内参基因,并在此基础上进一步分析二斑叶螨不同品系P450酶系CYP392E亚家族基因的表达量差异。【结果】在二斑叶螨SS,Av-R和Sp-R品系中稳定性最高的内参基因为ELFn。以ELFn为内参基因,CYP392E7基因相对表达量在二斑叶螨Av-R品系中显著高于SS品系(P<0.05),为后者的2.18倍,而在Sp-R品系和SS品系中差异不显著;其余基因的相对表达量在2个抗性品系中均没有增加,Av-R品系的CYP392E4,CYP392E9和CYP392E10基因以及Sp-R品系的CYP392E1和CYP392E9基因相对表达量甚至显著下调,分别为SS品系的48%,74%,65%,63%和73%。【结论】在二斑叶螨SS,Av-R和Sp-R品系中ELFn为理想的内参基因,Av-R品系CYP392E4,CYP392E7,CYP392E9和CYP392E10基因相对表达量的显著变化可能与二斑叶螨对阿维菌素的抗性形成有关,Sp-R品系CYP392E1和CYP392E9基因也可能与二斑叶螨对螺虫乙酯的抗性形成有一定联系。