幽门螺杆菌毒力因子CagA的基因表达调控机制研究进展

全球约有一半人口感染了幽门螺杆菌(Helicobacter pylori,H.pylori),特别是发展中国家的感染率极高。目前,幽门螺杆菌感染已被列为胃癌发生的高危因素。幽门螺杆菌感染的致病机制被认为与环境因素、宿主易感性和细菌毒力等因素之间复杂的相互作用有关。文章主要对幽门螺杆菌毒力因子细胞毒素相关基因(cytotoxin-associated gene A,cagA)表达调控的分子机制进行综述,以便更好地理解cagA的致病性,为今后预防和治疗由幽门螺杆菌所引起的疾病提供理论参考。

In silico prospective analysis of the medicinal plants activity on the CagA oncoprotein from Helicobacter pylori

BACKGROUND Colonization with Helicobacter pylori(H.pylori)has a strong correlation with gastric cancer,and the virulence factor CagA is implicated in carcinogenesis.Studies have been conducted using medicinal plants with the aim of eliminating the pathogen;however,the possibility of blocking H.pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed.This type of study is expensive and time-consuming,requiring in vitro and/or in vivo tests,which can be solved using bioinformatics.Therefore,prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein.AIM To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H.pylori.METHODS In this in silico study,the structures of the phenolic compounds(ligands)kaempferol,myricetin,quercetin,ponciretin(flavonoids),and chlorogenic acid(phenolic acid)were selected from the PubChem database.These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H.pylori infection.The three-dimensional structure model of the CagA oncoprotein of H.pylori(receptor)was obtained through molecular modeling using computational tools from the I-Tasser platform,employing the threading methodology.The primary sequence of CagA was sourced from GenBank(BAK52797.1).A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands,utilizing the GRaSP online platform.Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4(ADT)software,and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software.Two sets of simulations were performed:One involving the central region of CagA with phenolic compounds,and another involving the carboxy-terminus region of CagA with phenolic compounds.The receptor-ligand complexes were then analyzed using PyMol and BIOVIA Discovery Studio software.RESULTS The structure model obtained for the CagA oncoprotein exhibited high quality(C-score=0.09)and was validated using parameters from the MolProbity platform.The GRaSP online platform identified 24 residues(phenylalanine and leucine)as potential binding sites on the CagA oncoprotein.Molecular docking simulations were conducted with the three-dimensional model of the CagA oncoprotein.No complexes were observed in the simulations between the carboxy-terminus region of CagA and the phenolic compounds;however,all phenolic compounds interacted with the central region of the oncoprotein.Phenolic compounds and CagA exhibited significant affinity energy(-7.9 to-9.1 kcal/mol):CagA/kaempferol formed 28 chemical bonds,CagA/myricetin formed 18 chemical bonds,CagA/quercetin formed 16 chemical bonds,CagA/ponciretin formed 13 chemical bonds,and CagA/chlorogenic acid formed 17 chemical bonds.Although none of the phenolic compounds directly bound to the amino acid residues of the K-Xn-R-X-R membrane binding motif,all of them bound to residues,mostly positively or negatively charged,located near this region.CONCLUSION In silico,the tested phenolic compounds formed stable complexes with CagA.Therefore,they could be tested in vitro and/or in vivo to validate the findings,and to assess interference in CagA/cellular target interactions and in the oncogenic differentiation of gastric cells.

基于PSO_WT与改进的CAGA_CNN算法的心音识别研究

为探究复杂场景下心音信号的准确识别方案,提出了基于PSO_WT与改进的CAGA_CNN算法融合的方案。首先构造PSO_WT对采集的心音数据集进行去噪;其次将去噪后的心音数据转化为波形图进行特征提取;再者基于改进的CAGA_CNN网络对心音信号进行识别。为了验证本文提出算法的有效性,进行了模型的性能分析以及基于不同的算法模型进行验证。实验结果表明,本文算法具有较好的降噪能力,以及更高的识别精度和收敛速度。

自身免疫性胃炎并发结肠息肉患者CagA、胃黏膜功能和自身抗体的变化

目的分析自身免疫性胃炎并发结肠息肉患者CagA、胃黏膜功能和自身抗体的变化。方法纳入自身免疫性胃炎患者122例作为AIG组,另外收集同期萎缩性胃炎患者180例作为对照组。AIG组根据结肠是否有息肉,分为有、无增生性息肉组或有、无腺瘤性息肉组。比较各组血清胃泌素、细胞毒素相关基因A(CagA)、抗胃壁细胞抗体(PCA)、抗内因子抗体(IFA)、胃蛋白酶原Ⅰ/Ⅱ以及幽门螺杆菌感染情况。结果122例AIG患者中,73例患者幽门螺杆菌感染阳性,46例CagA阳性,43例PCA阳性,46例IFA阳性。AIG组结肠多发性增生性息肉和腺瘤性息肉发生率高于对照组(P<0.05)。有增生性息肉组幽门螺杆菌感染阳性率高于无增生性息肉组,有腺瘤性息肉组幽门螺杆菌感染阳性率和CagA阳性率高于无腺瘤性息肉组(P<0.05)。结论自身免疫性胃炎易伴有结肠增生性成腺瘤性息肉,可能与幽门螺杆菌感染有关。

Helicobacter pylori Virulence Genes cagA, babA2, and vacA Detection in Dyspeptic Patients from Burkina Faso

The diverse clinical presentation of Helicobacter pylori (H. pylori) infection results from the interaction between bacterial virulence, host genetics, socio-demographic and environmental factors. This study aimed to characterize Helicobacter pylori virulence genes and the associated behavioral factors among dyspeptic patients in Burkina Faso. Two hundred and fifty (250) stool samples were collected from patients with dyspepsia seen at health centers in Ouagadougou, Burkina Faso. Bacterial deoxyribonucleic acid (DNA) was extracted using a commercial kit. Virulence genes were detected using conventional multiplex Polymerase Chain Reaction with specific primers. The overall prevalence of Helicobacter pylori of the 250 participants was 91.20%. CagA virulence gene was present among 20.19% of individuals, while babA2 and vacA were detected respectively among 9.65% and 67.54% of the population positive for Helicobacter pylori. Among vacA subtypes, vacAs1 was the most frequent, with 39.04%, followed by vacAi1 (19.74%), vacAi2 (17.54%), and vacAs2 with 10.96%. Regarding vacAm1 and vacAm2, they were less frequent at 6.14% each. “Handwashing three times or less per day” significantly increased the risk of having vacAi2 allele and H. pylori rRNA16s, with p-values of 0.013 and 0.020, respectively. The consumption of non-tap water increases the risk of carrying the cagA virulence gene. Additionally, H. pylori-positive patients living with more than four (4) people in their household had about two times the risk of having the vacAs1 allele. The present study shows the detection of Helicobacter pylori cagA, vacA subtypes, and babA2 by stool a PCR method in Burkina Faso. The strong association between sanitary habits and virulence factors depicts the composite interaction between ecological factors, gastric mucosa, and bacteria. Therefore, the synergic action of these factors should be considered when aiming for bacterial eradication and gastric pathology cure.

镇江地区H pylori的cagA基因及其3′可变区结构的变化

目的:评估镇江地区H pylori临床株的cagA基因阳性率、了解菌株CagA蛋白的可能分型、其羧端可变区EPIYA的数目以及与临床结果之间有无关联.方法:培养分离来自临床胃十二指肠疾病患者的H pvlori,提取基因组DNA,通过PCR方法检测H pylori cagA基因的状况.随机选择不同病种的cagA基因阳性(cagA^+)的PCR产物.通过转化质粒,进行cagA^+PCR产物测序,通过ExPASY-Tranlation软件获得cagA基因相应的CagA蛋白的氨基酸序列.国际标准株NCTC11637的cagA基因以及CagA蛋白序列通过搜索NCBI(www.ncbi.nlm.nih.gov)数据库获得.结果:60株H pylori临床株中,56例为cagA^+,阳性率达93.3%.20例测序的结果表明,CagA蛋白结构可分为2种类型,19株东亚型和1株西方型.所有19株东亚型均为Yamaoka分型的A型,所有20例菌株的EPIYA的数目均为3个,与临床结果无关联.结论:cagA基因阳性率在不同病种之间无差异.镇江地区H pylori临床株的CagA蛋白的一级结构,与日本、韩国菌株一样,主要为东亚型,其CagA蛋白羧端可变区EPIYA数目均为3个,与临床结果无关联.

幽门螺杆菌cagA基因全长克隆及序列分析

目的 探索扩增cagA基因全长的PCR方法 ,克隆中国 2株胃癌幽门螺杆菌 (Helicobacterpylori,Hp)分离株和1株十二指肠溃疡分离株及国际标准株SS1的cagA基因 ,初步探讨cagA序列和磷酸化位点变异及其临床意义。方法 针对已知cagA基因两侧及cag致病岛右侧反转重复序列设计PCR引物 ,扩增cagA基因并克隆测序 ,分析已知cagA序列同源性及其酪氨酸磷酸化位点。结果 3株中国Hp分离株cagA氨基酸序列的同源性约为 94% (93 9%、94%、94 5 % ) ,并都有pY117/118/12 2和EPIYA A、B、D 4个酪氨酸磷酸化位点。SS1株cagA与西方菌株同源性大于 85 % ,而与中国菌株的同源性小于 80 % ,具有pY117/118/12 2和EPIYA A、B、C 4个酪氨酸磷酸化位点。结论 建立的PCR方法可扩增cagA基因全长。CagA序列变异和磷酸化位点具有地区聚类特征 ,但与Hp感染临床结局无特殊关联。

Analysis of Translocation of the CagA Protein and Induction of a Scattering Phenotype in AGS Cells Infected with Helicobacter pylori

Objective To investigate whether the presence of structured CagA proteins in Western- and Eastern-type Helicobacter pylori （H. pylori） induces different incidences of gastric diseases. Methods CagA and phosphorylatd CagA were expressed in AGS gastric epithelial cells infected with wild type and mutant strains. The ability of individual CagA was determined by immunoprecipitation and Western blot assay. Morphological changes of these cells were observed under microscope to evaluate the appearance of elongation hummingbird phenotype. Results The sizes of CagA proteins in different strains were different, and no phosphorylated CagA proteins were detected in wild-type strains. Meanwhile, the kinetics of CagA status in AGS infected with H. pylori was detected. The molecular weight of phosphorylated CagA with the same size of CagA proteins in H. pylori was different in infections with different wild-type strains. CagA and phosphorylated CagA increased in a time-dependent manner after the infection. The hummingbird phenotype with H. pylori for time-course was observed under microscope. Instead of HPK5 strain, the wild-type 26695 strain induced hummingbird phenotype in a time-dependent manner. Conclusion Translocation and phosphorylation of CagA are necessary, but not sufficient, for the induction of hummingbird phenotype in AGS cells.

Discovery of unique African Helicobacter pylori CagAmultimerization motif in the Dominican Republic

BACKGROUND Helicobacter pylori(H.pylori)colonizes the human stomach and is a major cause of peptic ulcer disease and gastric cancer.However,although the prevalence of H.pylori is high in Africa,the incidence of gastric cancer is low,and this phenomenon is called to be African enigma.The CagA protein produced by H.pylori is the most studied virulence factor.The carcinogenic potential of CagA is associated with the Glu-Pro-Ile-Tyr-Ala(EPIYA)patterns and CagAmultimerization(CM)motifs.AIM To better understand the EPIYA patterns and CM motifs of the cagA gene.METHODS Gastric mucosal biopsy specimens were obtained from 258 patients with dyspepsia living in the Dominican Republic,from which 120 H.pylori strains were cultured.After the bacterial DNA extraction,the EPIYA pattern and CM motif genotypes were determined using a polymerase chain reaction-based sequencing.The population structure of the Dominican Republic strains was analyzed using multilocus sequence typing(MLST).Peptic ulcer disease and gastric cancer were identified via endoscopy,and gastric cancer was confirmed by histopathology.Histological scores of the gastric mucosa were evaluated using the updated Sydney system.RESULTS All CagA-positive strains carried the Western-type CagA according to the identified EPIYA patterns.Twenty-seven kinds of CM motifs were observed.Although the typical Western CM motif(FPLKRHDKVDDLSKVG)was observed most frequently,the typical East Asian CM motif(FPLRRSAAVNDLSKVG)was not observed.However,“FPLRRSAKVEDLSKVG”,similar to the typical East Asian CM motif,was found in 21 strains.Since this type was significantly more frequent in strains classified as hpAfrica1 using MLST analysis(P=0.034),we termed it Africa1-CM(Af1-CM).A few hpEurope strains carried the Af1-CM motif,but they had a significantly higher ancestral Africa1 component than that of those without the Af1-CM motif(P=0.030).In 30 cagA-positive strains,the"GKDKGPE"motif was observed immediately upstream of the EPIYA motif in the EPIYA-A segment,and there was a significant association between strains with the hpAfrica1 population and those containing the“GKDKGPE”motif(P=0.018).In contrast,there was no significant association between the CM motif patterns and histological scores and clinical outcomes.CONCLUSION We found the unique African CM motif in Western-type CagA and termed it Africa1-CM.The less toxicity of this motif could be one reason to explain the African enigma.

幽门螺杆菌cagA基因3’端可变区和CagA蛋白EPIYA基序研究进展

细胞毒素相关基因A（cagA）编码CagA蛋白，是研究最多的幽门螺杆菌（H．pylori）基因之一。CagA蛋白经由Ⅳ型分泌系统进入Hpylori黏附的胃上皮细胞，其C-端发生酪氨酸磷酸化，磷酸化的CagA可引起细胞骨架重排、诱导细胞发生形态学变化、增强细胞动力，造成细胞异常运动和增殖．最终导致癌变。因此cagA阳性H．pylori菌株较cagA阴性菌株毒力更强。cagA基因3’端可变区重复序列数目的差异造成了cogA基因结构的多态性以及CagA蛋白大小、功能和细菌毒力（致病性）的差异。因此，cagA基因3’端可变区及其蛋白的EPIYA基序与H．pylori感染临床结果的相关性，成为目前H.pylori研究的热点之一。

幽门螺杆菌cagA基因和血清CagA抗体与VacA表达关系的研究

目的：探讨幽门螺杆菌cagA基因和血清CagA抗体与VacA表达的关系。方法：用聚合酶镇反应法（PCR）测定由62例慢性胃炎、消化性溃疡和胃癌患者胃窦粘膜分离获得Hp菌株；用酶免疫技术测定患者血清HpCagA抗体；用Hela细胞培养法测定Hp菌株VacA活性。结果：cagA基因阳性和阴性Hp菌株表达VacA阳性率分别为40．00％和33．33％（P＞0.05）；血清CagA抗体阳性和阴性患者感染Hp菌株体外产生VacA阳性率分别为33．33％和42．11％（P＞0.05）。结论：HpcagA基因和血清CagA抗体与VacA表达之间无相互依赖关系，vacA基因是一个独立的标志物。

CagA^+和CagA^-幽门螺杆菌致病作用的实验研究

目的用三种幽门螺杆菌菌株感染 C57BL/C 小鼠,观察不同菌株在小鼠胃内集落形成能力及感染后对小鼠胃粘膜组织学影响。方法:野生型 CPY3401株(CagA^+)与野生型 CPY3401株同源并去掉 CagA 的突变株(CagA^-)以及悉尼株(CagA^+),分别以0.5ml,10~9CFU/ml 细菌悬液通过胃管注入鼠胃。用 ELISA 法检测感染前后血清 IgG抗体水平。8周后处死小鼠,留取胃标本行组织病理检查。结果:(1)悉尼株和野生型株在鼠胃粘膜集落形成良好,突变株较差;(2)感染野生型株和悉尼株鼠胃粘膜固有层可见中到重度炎细胞浸润;(3)血清 IgG 抗体在感染后2周开始升高,5周达到高峰,2周、5周 t 值分别为悉尼株组7.41和17.44,野生型株组5.41和7.90,与对照组比较有极显著差异(P<0.01)。结论 CagA^+的悉尼株和野生型株在 C57BL/C 小鼠胃内集落形成良好,并引起明显的炎细胞浸润及产生高水平血清 IgG 抗体,对理解 CagA^+菌株在人胃感染中的致病作用及临床治疗有指导意义。C57BL/C 小鼠模型可用于 H.pylori 感染及相关疾病的研究。

仁术健胃颗粒对慢性萎缩性胃炎患者幽门螺杆菌及其cagA基因的影响

[目的]观察仁术健胃颗粒对慢性萎缩性胃炎 (CAG)患者幽门螺杆菌 (Hp)及Hp-cagA基因的影响 ,进一步探讨其治疗机制。[方法]选择符合CAG伴Hp 感染气虚热郁证的患者共128例 ,随机分为治疗组85例 ,cagA阳性者53例 ;对照组43例 ,cagA阳性者29例。治疗组予仁术健胃颗粒1包 ,冲服 ,3次/d ,对照组予胃复春4片 ,口服 ,3次/d。观察治疗前后临床症状、胃镜征象、病理、Hp及Hp-cagA基因的变化。[结果]治疗组临床、胃镜、病理有效率分别为91 8 %、71 8 %、65 9 % ,对照组分别为86 0 %、55 8 %、41 7 % ,治疗组胃镜、病理有效率高于对照组 ,有统计学意义 (P<0 05) ;治疗组Hp 的根除率、有效率分别为36 5 % (31/85)、77 6 % (66/85) ,对照组为30 2 % (13/43)、69 8 % (30/43) ,无统计学意义 (P>0 05) ;但治疗组Hp-cagA基因阴转率 (64 2 % ,34/53)高于对照组(41 4 % ,12/29) ,有统计学意义 (P<0 05)。[结论]仁术健胃颗粒对CAG有一定的治疗作用 ,其作用机制可能与根除Hp,减轻、削弱Hp

cagA基因对胃粘膜上皮细胞增殖和凋亡的影响

目的 观察不同基因型Hp感染对胃上皮细胞增殖和凋亡的影响,进而探讨Hp增加胃癌发生危险性的机制。 方法 研究对象为19例Hp阴性的慢性浅表性胃炎和37例Hp阳性的慢性浅表性胃炎患者,应用ki-67免疫组化技术评价胃幽门窦上皮细胞增生,用切口末端标记法(TUNEL)检测胃上皮细胞凋亡,应用聚合酶链反应(PCR)技术检测Hp的cagA基因。 结果 Hp阳性患者的增殖指数(LI)和凋亡指数(AI)显著高于Hp阴性者(17±4对7.3±3.3和11.3±3.8对6.6±1.2,P<0.01),cagA^+或cagA^-Hp患者的LI和AI均显著高于Hp^-患者,cagA^+Hp患者(n=27)的LI明显高于cagA^-Hp患者(n=10)(18.6±5.8对13.8±4.2,P<0.05),而AI则明显低于cagA^-Hp患者(8.9±3.2对12.2±4.6,P<0.01),LI和AI与胃粘膜炎症程度无明显关系。 结论 Hp感染诱导胃上皮细胞过度增殖和凋亡,cagA^+Hp与cagA^-Hp促增殖和凋亡作用的能力明显不同。

幽门螺杆菌cagA、vacA抗体与胃十二指肠疾病的相关性研究

目的 :探讨幽门螺杆菌 (Hp)毒力基因cagA、vacA抗体与胃十二指肠疾病之间的关系。方法 :采用免疫印迹法检测 440例胃十二指肠疾病患者血清中的cagA、vacA抗体。结果 :cagA、vacA抗体在 440例患者中的检出率分别为 73 %、37.0 %。在慢性胃炎 (CG)、十二指肠球部溃疡 (DU)、胃癌 (GC)患者中 ,cagA、vacA抗体的阳性率分别为 62 .9% ,76 .1 %、96 .9%与 33 .0 %、31 .0 %、62 .5 % ;经u检验显示 :慢性胃炎组与十二指肠球部溃疡组比较 ,无明显差异。胃癌组与慢性胃炎组、十二指肠球部溃疡组比较 ,有显著性差异。结论 :本文通过患者血清中Hp抗体 (cagA和vacA)的检测 ,推知其cagA和vacA抗体的表达状况 ,可为胃十二指肠疾病的诊断提供依据 。

幽门螺杆菌毒力因子CagA通过靶向SHARPIN促进炎症反应的机制研究

目的幽门螺杆菌(H.pylori)引起的慢性炎症是胃癌的主要原因之一,本研究旨在探讨幽门螺杆菌的重要毒力因子细胞毒素相关蛋白A(CagA)促炎的作用及其调控机制。方法采用质谱鉴定CagA在AGS细胞内的相互作用蛋白,并通过免疫共沉淀、免疫荧光验证其相互作用。通过使用siRNA敲低后,免疫印迹法检测通路蛋白表达、qRT-PCR检测炎症因子mRNA水平、ELISA检测蛋白水平。使用血红素-伊红染色法(H&E)检测临床样本中CagA诱导的炎症反应。结果CagA与SHARPIN具有相互作用。与CagA敲除株相比,CagA激活了NF-κB信号通路并上调了炎症因子IL-6、IL-8、TNF-α的mRNA水平和蛋白表达(P均<0.05)。通过siRNA敲低SHARPIN后,炎症水平降低、NF-κB信号被部分抑制。临床样本中CagA^(+)样本炎症反应显著增加。结论CagA促进宿主炎症反应,干扰SHARPIN可部分抑制CagA所致炎症反应,表明CagA通过与SHARPIN结合这一新机制激活NF-κB信号通路促炎。

上海市崇明地区幽门螺杆菌耐药性分析及cagA基因检测

目的探讨上海市崇明地区含细胞毒素相关基因A(cagA)的幽门螺杆菌(Hp)的感染情况及cagA基因与Hp的耐药性关系。方法对150株临床分离菌株,采用PCR法检测Hp的cagA基因,同时采用纸片扩散法作药敏试验。结果崇明地区Hp对甲硝唑、替硝唑、阿莫西林、克拉霉素、阿奇霉素和呋喃唑酮的耐药率分别为32%、10、2、0、0和0。78.7%的Hp菌株含有cagA基因。结论本地区阿莫西林、阿奇霉素、呋喃唑酮可作为根除Hp的首选药物。本地区Hp感染以Ⅰ型菌株为主,含cagA基因Hp菌株对甲硝唑耐药率明显低于不含cagA基因Hp菌株。

幽门螺杆菌及其cagA因子对胃粘膜中原癌基因蛋白表达的影响

目的 :探讨幽门螺杆菌 (Hp)感染特别是其细胞毒素相关基因 (cagA因子 )与胃粘膜中bcl 2、Bax、p2 1 WAF1、p16 MTS1蛋白表达异常的关系 ,从而从分子水平初步探讨cagA是否为一致癌因子及其可能的致癌的机理。方法 :1、利用血抗Hp IgG、RUT、PCR Hp DNA 3种方法检测 2 70例病人的Hp感染情况及cagA+ Hp感染情况 ;2、利用免疫组化S P法检测胃癌演化系列胃粘膜中bcl 2、Bax、p2 1 WAF1、p16 MTS1蛋白的表达 ;3、利用SPSS统计软件包作统计学分析处理。结果 :1、在CSG、CAG、IM阶段 ,Hp感染促进胃粘膜中bcl 2、Bax的表达 ,cagA因子促进bcl 2、Bax、p2 1 WAF1、p16 MTS1的表达 ,(P <0 0 5 ) ;在胃癌阶段 ,Hp感染与胃腺癌粘膜中bcl 2、p2 1 WAF1、p16 MTS1的低表达相关 (P <0 0 5 ) ,但与cagA因子无关 (P >0 0 5 ) ;2、在男性CSG、CAG、IM系列胃粘膜中bcl 2、Bax表达先高后低 ,与cagA+ Hp感染率呈正相关 ,而 p16 MTS1、p2 1 WAF1表达先低后高 ,与cagA+ Hp感染率呈负相关 (P <0 0 5 )。结论 :Hp的cagA因子可能通过影响癌前病变患者胃粘膜中bcl 2、Bax、p2 1 WAF1、p16 MTS1的表达 ,成为胃腺癌发生的“启动子”之一 ;Hp可能通过非cagA因子途径影响bcl 2、p2 1 WAF1、p16 MTS1的表达 。

耐甲硝唑幽门螺杆菌cagA基因检测与rdxA基因突变研究

目的研究cagA基因、rdxA基因变异与幽门螺杆菌(Hp)甲硝唑耐药的关系。方法收集临床分离Hp 180株,用E-test法检测对甲硝唑的最低抑菌浓度(MIC),PCR扩增cagA、rdxA基因,并对rdxA基因进行测序。结果幽门螺杆菌对甲硝唑的耐药率为43.3%,其中甲硝唑高水平耐药菌54株,占69.2%;rdxA基因突变率为56.7%;cagA阳性菌中高耐药菌所占的比例和rdxA基因的突变率均明显高于cagA阴性菌。结论本地区幽门螺杆菌感染以高毒力菌株为主,rdxA基因突变在cagA基因阳性菌对甲硝唑产生高水平耐药可能起一定作用。