髓样分化蛋白-2及Toll样受体4在星形细胞瘤中的表达及临床意义

目的 检测不同级别星形细胞瘤中髓样分化蛋白-2(MD2)和Toll样受体4(TLR-4)的表达,并探讨其临床意义.方法 收集2019年1月 ～2020年8月于山东国欣颐养集团新汶中心医院接受手术切除治疗的低级别星形细胞瘤(LGA)患者50例及高级别星形细胞瘤(HGA)患者50例,所有患者的肿瘤组织样本于术中离体后立刻保...     

Toll样受体4与大鼠肺泡巨噬细胞内毒素耐受性的实验研究

目的　观察大鼠肺泡巨噬细胞对内毒素 (LPS)重复刺激的耐受性与其Toll样受体 4(TLR4)表达的变化 ,研究两者之间的联系。方法　将 30只Wistar雄性大鼠分离所得肺泡巨噬细胞 ,用随机数字表法分为正常对照组 (A组 ) ,LPS单次刺激组 (B组 )和LPS 2次重复刺激组 (C组 )。用酶联免疫吸附测定 (ELISA)法和逆转录 聚合酶链反应 (RT PCR)法分别检测各组大鼠肺泡巨噬细胞分泌肿瘤坏死因子α(TNF α)及TLR4、白细胞介素 1 0 (IL 1 0 )、IL 1 8mRNA表达的变化 ,WesternBlot检测TLR4蛋白表达的变化。结果　大鼠肺泡巨噬细胞TNF α分泌和TLR4、IL 1 0、IL 1 8mRNA表达及TLR4的蛋白表达水平 ,A组分别为 (0 4 5 0± 0 0 1 0 ) μg/L、1 1 6± 0 0 4、0 97± 0 0 3、1 32 0± 0 0 2 0、5 8 1± 0 4 ;B组分别为 (0 76 0± 0 0 30 ) μg/L、2 1 8± 0 0 9、1 83± 0 0 7、2 0 6 0± 0 0 6 0、1 4 8.3± 1 4 ;B组与A组比较差异有显著性 (P <0 0 1 ) ;C组分别为 (0 4 90± 0 0 5 0 ) μg/L、1 2 3± 0 0 3、1 1 5± 0 0 5、1 1 70± 0 0 4 0、96 5±0 7;C组与B组比较差异也有显著性 (P <0 0 5或 <0 0 1 )。结论　LPS重复刺激可使大鼠肺泡巨噬细胞对LPS产生耐受性 ;LPS耐受性的产生与TLR4表达     

髓样分化蛋白2对重症急性胰腺炎的影响

脂多糖（LPS）是革兰氏阴性菌（G-）细胞壁的主要成分,它能被Toll样受体4（TLR4）所识别,并且TLR4是LPS跨膜信号转导的主要受体。已有研究表明,TLR4的表达在发生胰腺炎的胰腺中存在上调趋势,且急性坏死性胰腺炎时,肝、肺等组织中TLR4 mRNA的表达明显增强。所以,在SIRS和早期MODS,TLR4受体的激动即可被认为是诱导炎症反应失控的最初因素之一。本文主要就髓样分化蛋白2（MD2）在TLR4信号转导过程中的重要作用,及在其诱导下产生的炎症反应对重症急性胰腺炎（SAP）的影响和临床意义加以阐述。     

缬沙坦对糖尿病大鼠动脉Toll样受体4和髓样分化因子88表达的影响

P<0.01),糖尿病和缬沙坦组间血糖差异无统计学意义(P>0.05);糖尿病组大鼠血管组织中TLR4和Myd88 mRNA与蛋白的表达明显高于正常对照组(均P<0.01),而缬沙坦组明显低于糖尿病组(均P<0.01).结论 缬沙坦降低糖尿病大鼠动脉血管组织中TLR4和Myd88表达,可能对糖尿病血管早期的炎性改变起防治作用.     

黄芩苷对脂多糖诱导的巨噬细胞Toll样受体4表达的影响

目的 研究黄芩苷对脂多糖诱导的小鼠巨噬细胞Toll样受体4和其下游信号分子抑制蛋白kB以及效应分子肿瘤坏死因子α表达的影响.方法 分别用脂多糖(终浓度1 mg/L)或脂多糖+黄芩苷(终浓度10、50和100 μmol/L)处理生长良好的小鼠巨噬细胞RAW264.7,逆转录聚合酶链反应和Western Blot检测细胞Toll样受体4表达情况和抑制蛋白kB含量变化,酶联免疫吸附法检测细胞上清液中肿瘤坏死因子α的浓度.结果 脂多糖刺激RAW264.7细胞可导致Toll样受体4表达增高,促进抑制蛋白kB降解,上调肿瘤坏死因子α表达;黄芩苷预处理能降低脂多糖诱导的Toll样受体4表达增高,降低抑制蛋白kB降解,下调肿瘤坏死因子α分泌.结论 黄芩苷可通过抑制Toll样受体4表达和降低抑制蛋白kB降解,影响Toll样受体4/抑制蛋白kB-核因子kB炎症信号途径,阻碍炎症因子肿瘤坏死因子α的生成,发挥抗炎作用,这可能是其抗动脉粥样硬化的作用机制之一.     

维生素K_2对大鼠血管平滑肌细胞钙化及Toll样受体2和4表达的影响

目的探讨维生素K_2对血管平滑肌细胞(VSMC)钙化及Toll样受体(TLR)2和TLR4表达的影响。方法体外培养A7r5VSMC分为正常组(基础培养液),钙化组(加入10mmol/Lβ磷酸甘油),干预组(钙化基础上加入维生素K_210-6 mmol/L),各组均干预14d。Von Kossa染色观察VSMC钙化发生情况;检测细胞钙含量和碱性磷酸酶(ALP)活性;实时定量PCR及Western blot检测TLR2和TLR4mRNA和蛋白表达水平。结果钙化组细胞钙含量及ALP活性较正常组分别增加11.5倍和9.3倍(P<0.01);干预组细胞钙含量及ALP活性较钙化组分别减少1.5倍和2.3倍(P<0.01)。与正常组比较,钙化组细胞TLR2、TLR4蛋白及mRNA表达升高;与钙化组比较,干预组细胞TLR2、TLR4蛋白及mRNA表达降低(P<0.05,P<0.01)。结论维生素K_2抑制细胞钙化的作用可能与TLR2和TLR4表达的下调有关。     

实验性结肠炎大鼠Toll样受体2和4表达及益生菌治疗的作用

目的 探讨和分析实验性结肠炎大鼠结肠Toll样受体2(TLR2)和Toll样受体4(TLR4)的表达及意义,并分析益生菌治疗的作用.方法 30只雄性Wistar大鼠均分为正常对照组(NC组)、模型对照组(UC组)和益生菌治疗组(PC组).UC和PC组建立2,4,6-三硝基苯磺酸(TNBS)实验性结肠炎大鼠模型.PC组大鼠给予双歧三联活菌悬液(2.2×109 CFU/只)治疗,1次/d,共4周.光镜下观察肠黏膜炎性反应并评分.Western印迹法和实时荧光定量PCR法检测大鼠结肠TLR2和TLR4蛋白及mRNA表达,分析其变化及益生菌治疗的作用.结果 NC、PC和UC组炎性反应评分分别为4.35±0.88、10.25±1.36和7.94±0.85.PC组炎性反应评分较UC组明显改善(P＜0.05),但高于NC组水平(P＜0.01).NC、UC、PC组TLR2和TLR4蛋白表达水平分别为10.26±4.24、47.20±4.62、36.64±3.67和8.16±4.50、25.84±4.46、19.71±3.28.二者在UC组的表达明显高于NC组(P＜0.01)和PC组(P＜0.05),PC组高于NC组(P＜0.01).NC、UC、PC组TLR2和TLR4 mRNA表达水平分别为240±140、10 570±2690、6640±1420和210±110、8580±2710、5290±1540.二者在UC组的表达明显高于PC组(P＜0.05)和NC组(P＜0.01),PC组高于NC组(P＜0.01).结论 实验性结肠炎大鼠结肠TLR2和TLR4表达明显增高,提示肠腔内抗原摄取增多.双歧三联活菌可明显降低二者的表达水平,提示该益生菌可能通过降低TLR2和TLR4表达减少肠腔抗原的摄取.     

阿托伐他汀对脓毒症大鼠急性肺损伤的保护作用及对细胞炎性蛋白-2和Toll样受体-4表达的影响

目的探讨阿托伐他汀对脓毒症大鼠急性肺损伤(ALI)的保护作用及其相关机制。方法采用盲肠结扎穿孔(CLP)方法构建大鼠脓毒症ALI模型,40只大鼠随机分为假手术组(S组)、模型组(M组)、阿托伐他汀低剂量组(L组,20 mg/kg)和阿托伐他汀高剂量组(H组,40 mg/kg),阿托伐他汀治疗组术后6 h和18 h腹腔注射不同剂量的阿托伐他汀,S、M组同时间给予等量的生理盐水腹腔注射。术后20 h处死大鼠收集血液及肺组织标本。测定实验各组动脉血气指标、肺水含量、支气管肺泡灌洗液中蛋白含量及细胞计数;酶联免疫吸附(ELISA)法检测血清中细胞炎性蛋白(MIP)-2及Toll样受体(TLR)-4水平;反转录PCR方法检测肺组织MIP-2及TLR-4 mRNA的表达。结果与M组比较,动脉血气指标、肺水含量、支气管肺泡灌洗液中蛋白含量及细胞计数在L组、H组均显著改善(P0.05),且H组改善更明显(P0.05)。与M比较,阿托伐他汀干预组血清MIP-2及TLR-4水平和肺组织MIP-2及TLR-4 mRNA的表达均明显降低(P0.05),且H组改善更明显(P0.05)。结论阿托伐他汀对脓毒症大鼠ALI具有保护作用,这种保护作用可能与其抑制MIP-2及TLR-4表达有关。     

白蛋白治疗对小鼠脑缺血早期脑组织Toll样受体4和骨髓分化因子88 mRNA表达的影响

目的研究人血白蛋白治疗对局灶性脑缺血再灌注小鼠脑组织Toll样受体4(TLR4)和骨髓分化因子88(MyD88)mRNA表达的影响。方法健康雄性成年昆明小鼠54只,随机分为假手术组(14只)、生理盐水组(20只)和白蛋白组(20只),每组又均分为再灌后6、24 h 2个时间点。采用左侧大脑中动脉线栓法制备小鼠局灶性脑缺血再灌注模型,RT-PCR法检测左侧脑组织TLR4、MyD88 mRNA的表达水平,并进行神经功能缺损评分。结果生理盐水组和白蛋白组脑缺血再灌注后6、24 h TLR4、MyD88 mRNA表达水平明显高于假手术组,且24 h表达水平升高更明显(P<0.05);但白蛋白组6、24 h TLR4、MyD88 mRNA表达量明显低于生理盐水组(P<0.05);24 h白蛋白组小鼠的神经功能缺损评分与生理盐水组比较有明显改善(P<0.05);24 h TLR4、MyD88 mRNA表达水平与神经功能缺损评分呈正相关(r=0.92,r=0.85,P<0.05)。结论白蛋白治疗可以下调脑缺血早期脑组织高表达的TLR4、MyD88 mRNA的水平,改善脑缺血后小鼠神经功能缺损。     

Toll样受体4及Tollip蛋白在大肠癌中的表达及临床意义

目的探讨Toll样受体4（TLR4）及Tollip蛋白在大肠癌发生、发展过程中的作用。方法采用免疫组化SP法检测TLR4和Tollip蛋白在51例大肠癌癌组织和20例癌旁正常组织中的表达,并分析两者与大肠癌临床分期、病理分级的相关性。结果TLR4及Tollip蛋白在大肠癌组织中的表达显著强于癌旁正常组织,且两者表达随肿瘤临床病理分期进展及病理分级降低而升高（P〈0．01）。结论TLR4、Tollip蛋白在大肠癌发生、发展过程中发挥一定免疫作用,可作为判断大肠癌进展程度的参考指标。     

Significance of MD-2 and MD-2B expression in rat liver during acute cholangitis

AIM: To investigate the expression of myeloid differentiation protein-2 (MD-2), MD-2B (a splicing isoform of MD-2 that can block Toll-like receptor 4 (TLR4)/MD-2 LPS-mediated signal transduction) and TLR4 in the liver of acute cholangitis rats.METHODS: Male Sprague-Dawley rats (SPF level) were randomly divided into four groups: (A) sham-operated group; (B) simple common bile duct ligation group; (C) acute cholangitis group; and (D) acute cholangitis anti-TLR4 intervention group (n = 25 per group). Rat liver tissue samples were used to detect TLR4, MD-2 and MD-2B mRNA expression by fluorescence quantitative PCR in parallel with pathological changes.RESULTS: In acute cholangitis, liver TLR4 and MD-2 mRNA expression levels at 6, 12, 24, 48 and 72 h were gradually up-regulated but MD-2B mRNA expression gradually down-regulated (P < 0.05). After TLR4 antibody treatment, TLR4 and MD-2 mRNA expression were lower compared with the acute cholangitis group (P < 0.05). However, MD-2B mRNA expression was higher than in the acute cholangitis group (P < 0.05). MD-2 and TLR4 mRNA expressions were positively correlated (r = 0.94981, P < 0.05) and MD-2B mRNA expression was negatively correlated with MD-2 and TLR4 mRNA (r = -0.89031, -0.88997, P < 0.05).CONCLUSION: In acute cholangitis, MD-2 plays an important role in the process of TLR4- mediated inflammatory response to liver injury while MD-2B plays a negative regulatory role.     

吸入一氧化氮对脂多糖所致大鼠急性肺损伤环氧合酶-2及TOLL样受体4表达的影响

目的 建立脂多糖致大鼠急性肺损伤的模型,观察一氧化氮对大鼠气道环氧合酶-2(cox-2)和Toll样受体4(TLR4)的分布及表达的影响.方法 健康雄性SD大鼠24只,按随机数字表法分为正常对照组、单用脂多糖(脂多糖组)、脂多糖加NO 20×10-6mg/L(低浓度NO组),脂多糖加NO 100×10-6mg/L(高浓度NO组).气管内滴注脂多糖(5 mg/kg)建立大鼠急性肺损伤模型.观察6 h后的肺水肿程度、免疫组织化学(SP染色)和实时荧光定量PCR检测肺组织中COX-2和TLR4的表达,以及分别吸入20×10-6、100×10-6mg/L浓度NO后的影响.所得数据采用单因素方差分析进行统计学分析,多个样本均数之间的两两比较采用LSD-t检验.结果 COX-2和TLR4在对照组大鼠气道内有广泛的分布和表达.脂多糖组大鼠肺水肿程度明显高于对照组,其主支气管和肺内细支气管上皮细胞内COX-2(6.5±2.8)及TLR4(44.9±11.3)表达高于对照组(分别为2.8 4±0.8、2.1±0.7),差异有统计学意义(t值分别为3.003、10.480,均P<0.01).低浓度NO组肺水肿程度明显减轻,其COX-2表达量(5.0±2.0)低于脂多糖组,但差异无统计学意义(t=1.227,P>0.05).而低浓度NO组TLR4(16.2±3.8)的表达量与脂多糖组(44.9±11.3)比较差异具有统计学意义(t=7.030,P<0.001).结论 COX-2和TLR4在大鼠气道内广泛分布,脂多糖刺激可使COX-2和TLR4的表达增强,吸入适当浓度NO可降低由脂多糖引起的COX-2和TLR4表达的增高.     

TLR2 and TLR4 polymorphisms influence mRNA and protein expression in colorectal cancer

AIM: To evaluate the effect of promoter region polymorphisms of toll-like receptor(TLR)2-196 to-174 del and TLR4-1607T/C(rs10759932) on m RNA and protein expression in tumor tissue and of TLR4+896A/G(rs4986790) on colorectal cancer(CRC) risk.METHODS: The TLR2-196 to-174 del polymorphism was investigated using allele-specific polymerase chain reaction(PCR) and the TLR4-1607T/C and TLR4+896A/G by PCR-restriction fragment length p o l y m o r p h i s m( R F L P). W e g e n o t y p e d 4 3 4 D N A samples from 194 CRC patients and 240 healthy individuals. The m RNA relative quantification(RQ) was performed in 40 tumor tissue samples by quantitative PCR Taq Man assay, using specific probes for TLR2 and TLR4 genes, and ACTB and GAPDH reference geneswere used as endogenous controls. Protein expression was analyzed by immunohistochemistry with specific primary antibodies.RESULTS: No association was found for TLR4-1607T/C and TLR4+896A/G by three statistical models(logadditive, dominant and recessive). However, based on dominant and log-additive models, the polymorphic variant TLR2-196 to-174 del was associated with increased CRC risk [dominant: odds ratio(OR) = 1.72, 95%CI: 1.03-2.89; P = 0.038 and log-additive: OR =1.59, 95%CI: 1.02-2.48; P = 0.039]. TLR2 m RNA expression was increased in tumor tissue(RQ = 2.36) when compared to adjacent normal tissue(RQ = 1; P 0.0001), whereas the TLR4 m RNA showed a basal expression(RQ = 0.74 vs RQ = 1, P = 0.452). Immunohistochemistry analysis of TLR2 and TLR4 protein expression was concordant with the findings of m RNA expression. In addition, the TLR2-196 to-174 del variant carriers showed m RNA relative expression 2.19 times higher than wild-genotype carriers. The TLR2 protein expression was also higher for the TLR2-196 to-174 del variant carriers [117 ± 10 arbitrary unit(a.u.) vs 95 ± 4 a.u., P = 0.03]. However, for the TLR4-1607T/C polymorphism no significant difference was found for both m RNA(P = 0.56) and protein expression(P = 0.26).CONCLUSION: Our findings suggest that TLR2-196 to-174 del polymorphism increases TLR2 m RNA expression and is associated with higher CRC risk, indicating an important role in CRC genetic susceptibility.     

Detailed Molecular Interactions between Respiratory Syncytial Virus Fusion Protein and the TLR4/MD-2 Complex In Silico

Molecular interactions between respiratory syncytial virus (RSV) fusion protein (F protein) and the cellular receptor Toll-like receptor 4 (TLR4) and myeloid differentiation factor-2 (MD-2) protein complex are unknown. Thus, to reveal the detailed molecular interactions between them, in silico analyses were performed using various bioinformatics techniques. The present simulation data showed that the neutralizing antibody (NT-Ab) binding sites in both prefusion and postfusion proteins at sites II and IV were involved in the interactions between them and the TLR4 molecule. Moreover, the binding affinity between postfusion proteins and the TLR4/MD-2 complex was higher than that between prefusion proteins and the TLR4/MD-2 complex. This increased binding affinity due to conformational changes in the F protein may be able to form syncytium in RSV-infected cells. These results may contribute to better understand the infectivity and pathogenicity (syncytium formation) of RSV.     

免疫抑制剂对小鼠肺泡巨噬细胞抗曲霉感染相关受体mRNA表达的影响

目的 探讨免疫抑制剂对小鼠肺泡巨噬细胞抗曲霉感染相关受体mRNA表达的影响.方法 30只昆明小鼠随机分为2组:正常对照组(6只)和免疫抑制组(24只,环磷酰胺150 mg/kg腹腔注射).免疫抑制组小鼠注射环磷酰胺后4 h、8 h、16 h及24 h,分别随机取6只进行支气管肺泡灌洗,收集肺泡巨噬细胞.正常对照组小鼠注射生理盐水24 h后处死,收集肺泡巨噬细胞.使用逆转录-聚合酶链反应检测小鼠肺泡巨噬细胞Toll样受体2(TLR2)、TLR4、树突状细胞相关C型凝集素1(Dectine-1)mRNA表达变化.结果 与正常对照组比较,腹腔注射环磷酰胺4 h后,TLR2 mRNA表达即出现显著下降(P＜0.01);在腹腔注射环磷酰胺8 h后TLR4 mRNA表达出现显著下降(P＜0.01);Dectine-1 mRNA在腹腔注射环磷酰胺后无明显变化.结论 免疫抑制剂环磷酰胺能够下调肺泡巨噬细胞抗曲霉感染相关受体TRL2和TLR4 mRNA的表达,对Dectine-1 mRNA的表达未见明显影响.     

Analysis of TLR4 and TLR2 polymorphisms in inflammatory bowel disease in a Guangxi Zhuang population

AIM: To study the polymorphisms of toll-like receptor 4 (TLR4) gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp and susceptibility to inflammatory bowel disease (IBD) in the Zhuang population from Guangxi, China.METHODS: A case-control study was performed from February 2007 to October 2011 which included 146 Zhuang patients with IBD in the experimental group and 164 healthy Zhuang subjects who acted as the control group. All patients and healthy subjects were from the Guangxi Zhuang Autonomous Region of China. Genomic DNA was extracted from intestinal tissue by the phenol chloroform method. TLR4 gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp were amplified by polymerase chain reaction (PCR), and then detected by PCR-restriction fragment length polymorphism (RFLP).RESULTS: The TLR4 gene Asp299Gly was digested using Nco I restriction enzyme, and a single band of 249 bp was observed which showed that it was a wild type (AA). The TLR4 gene Thr399Ile was digested using Hinf Irestriction enzyme and only the wild type (CC) was detected. In addition, the TLR2 gene Arg677Trp was digested using Aci I restriction enzyme and only the wild type (CC) was detected. The TLR2 gene Arg753Gln was digested using Pst I restriction enzyme. Only the wild type (GG) as a single band of 254 bp was observed during RFLP. Overall, no heterozygous or homozygous single nucleotide polymorphism mutations were found in patients with Crohn’s disease and ulcerative colitis both in the TLR4 gene Asp299Gly, Thr399Ile and the TLR2 gene Arg677Trp, Arg753Gln in the Zhuang population from the Guangxi Zhuang Autonomous Region of China.CONCLUSION: The TLR4 gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp polymorphisms may not be associated with IBD in the Zhuang population from the Guangxi Zhuang Autonomous Region of China.     

TLR2对小鼠IL-17分泌的影响及其在抗结核免疫中的作用

目的通过检测TLR2-/-小鼠和WT小鼠脾脏CD4+T淋巴细胞在TLR2结核菌配体刺激下IL-17的表达水平,阐明TLR2对Th17细胞的作用及其在抗结核免疫的意义。方法选取TLR2-/-小鼠和WT小鼠各6只,分离出小鼠脾脏淋巴细胞与TLR2结核菌配体(19KD脂蛋白、Mtb、Pam3Cys-SK)共刺激培养3 d,通过流式细胞技术检测CD4+T细胞IL-17的表达水平。结果在TLR2结核菌配体刺激下,WT小鼠的CD4+T细胞分泌的IL-17高于TLR2-/-小鼠,在Mtb刺激下两者之间有统计学差异(P<0.05)。结论结核菌通过TLR2直接影响IL-17表达,从而发挥抗结核免疫作用。     

Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population

AIM: To investigate toll-like receptor 2 (TLR2) -196 to -174 del, and TLR4 (+896A/G rs4986790 and +1196C/T rs4986791) polymorphisms at risk of chronic gastritis and gastric cancer in a Brazilian population and association of gastric lesions with risk factors such as smoking, alcohol intake and Helicobacter pylori infection.METHODS: In this case-control study, polymorphism at TLR2 -196 to -174 del was investigated by using the allele-specific polymerase chain reaction (PCR) method, while the PCR-restriction fragment length polymorphism technique was carried out to identify the TLR4 (rs4986790 and rs4986791) genotypes in 607 Brazilian individuals (208 with chronic gastritis-CG, 174 with gastric cancer-GC and 225 controls -C).RESULTS: The single nucleotide polymorphisms TLR4+1196C/T was not associated with risk of chronic gastritis or gastric cancer and the homozygous genotypes TLR4+896GG and TLR4+1196TT were absent in the studied population. However, the frequency of TLR2 -196 to -174 ins/del + del/del and TLR4+896AG genotypes was significantly higher (P < 0.01 and P = 0.01, respectively) in the cancer group (33.4% and 11.5%, respectively) than in the control group (16.9% and 4.5%, respectively). It was also observed that the G-C haplotype of the TLR4+896A/G+1196C/T (P = 0.02) and the combination of variant alleles of the TLR2/TLR4+896G (P = 0.02) are associated with susceptibility to gastric cancer. In addition, the multiple logistic regression showed that male gender [odds ratio (OR) = 2.70; 95% CI: 1.66-4.41; P < 0.01], alcohol intake (OR = 2.93; 95% CI: 1.76-4.87; P < 0.01), TLR2 -196 to -174 del (OR = 2.64; 95% CI: 1.56-4.44; P < 0.01) and TLR4+896G (OR = 3.19; 95% CI: 1.34- 7.61; P < 0.01) polymorphisms were associated with a higher susceptibility to developing this neoplasm.CONCLUSION: Our data indicate that TLR2 -196 to -174 del and TLR4+896G may increase the risk of gastric cancer in a Brazilian population.     

Toll样受体4在胰腺癌组织中的表达及其与肿瘤血管生成的关系

目的 探讨Toll样受体4(TLR4)在胰腺癌组织中的表达及其与肿瘤血管生成的关系.方法 采用免疫组化SP法检测62例经病理证实的胰腺癌手术切除标本及35例癌旁正常胰腺组织中TLR4蛋白表达,采用CD31抗体标记微血管内皮细胞,计算微血管密度(MVD).分析TLR4蛋白表达与胰腺癌临床病理特征以及MVD的相关性.结果 胰腺癌组织TLR4蛋白阳性表达率和MVD分别为74.2％ (46/62)和47.3±13.5,均显著高于正常胰腺组织的17.1％ (6/35)和12.6±4.8(P值均＜0.01).有淋巴结转移的胰腺癌组织中TLR4蛋白阳性表达率为83.8％,显著高于无淋巴结转移的60.0％(P=0.036);TNM分期为Ⅲ+Ⅳ期的胰腺癌组织中TLR4蛋白阳性表达率为85.3％,显著高于Ⅰ+Ⅱ期的60.7％(P =0.028).MVD与肿瘤的大小、淋巴结转移及TNM分期密切相关(P值分别为0.008、0.036、0.010).胰腺癌TLR4蛋白表达与MVD呈显著正相关(Υ=0.534,P＜0.01).结论 TLR4参与胰腺癌的发生、发展,其机制可能与促进肿瘤血管生成有关.