Toll样受体4在急性肺损伤中的作用

目的观察Toll样受体4(toll-like receptor 4,TLR4)基因突变型小鼠与野生型小鼠内毒素攻击致急性肺损伤(acute lung injury,ALI)的差异,分析TLR4在ALI中的作用。方法采用TLR4基因突变小鼠(C3H/HeJ品系,TLR4~(-/-)及野生型小鼠(CBA品系,TLR4~( / )),用内毒素攻击复制小鼠ALI模型,用显微病理及肺干湿重比(W/D)分析肺损伤程度,检测肺组织髓过氧化物酶(MPO)水平,探讨损伤差异的可能机制。结果用1,5 mg·kg~(-1)LPS溶液经尾静脉注射复制ALI模型,结果示TLR4突变小鼠肺组织大体及显微病理损伤较野生型小鼠减轻,同时肺组织水肿(W/D)亦较野生小鼠减轻,尤其是在大剂量(5mg·kg~(-1))时,差异有显著性[(4．08±0．1)vs．(4．55±0．2),n=10,t=12．71,P＜0．01]。突变小鼠肺组织PMN浸润水平较野生型低[MPO：1 mg·kg~(-1)组,(20．73±4．58)vs．(39．97±3．66),n=10,t=13．43,P＜0．01];5 mg·kg~(-1)组,[(24．0±3．94)vs．(48．5±4．07),n=10,t=15．33,P＜0．01],且两者均较假手术组高。结论TLR4可能通过介导中性粒细胞肺内聚集而导致ALI的发生发展。     

幽门螺杆菌致病机制分子生物学研究进展

1994年幽门螺杆菌已经被世界卫生组织国际癌症研究机构（IARC）列为Ⅰ类致癌原。据报道,在发达国家40%成人感染幽门螺杆菌（Hp）,发展中国家成人Hp感染率高达90%。我国属发展中国家,Hp感染率高,全国性流行病学调查结果显示了我国各省Hp感染率为40%～90%,平均为59%。     

Toll样受体4与急腹症

Toll样受体4(TLR4)为研究最广的先天性免疫受体,主要与免疫、感染相关;已证明与多种感染性疾病、急性脏器损伤及某些肿瘤相关。近年来发现TLR4与新生儿坏死性小肠结肠炎、急性胰腺炎、腹膜炎等急腹症密切相关。现对其研究进展加以综述,为急腹症进一步的研究提供向导。     

Toll样受体在丙型肝炎慢性化中的作用机制

世界上约有3%的人感染了丙型肝炎病毒(HCV),其中55%～85%的感染者发展成为慢性感染[1].不同的个体感染后的自然病程和结局存在较大差异.Toll样受体(TLRs)能够识别病毒的单链RNA,在病毒感染中参与病原体的识别和宿主反应.本文就TLRs在慢性丙型肝炎(CHC)发病机制中的研究进行综述.     

强直性脊柱炎髋关节病变中Toll样受体4表达的初步研究

目的 研究强直性脊柱炎（AS）髋关节病变中滑膜Toll样受体2和4（TLR2和TLR4）等受体的表达,以探讨髋关节病变的发病机制.方法 免疫组化染色法检测AS患者及对照组患者滑膜组织中TLR2、TLR4、髓样分化因子88（MyD88）、NFκB-p65表达情况.结果 AS组滑膜组织中TLR4、NFκB-p65表达阳性,TLR2、MyD88表达阴性,而对照组只NFκB-p65表达阳性,TLR2、TLR4、MyD88表达阴性.结论 AS患者髋关节病变存在TLR4高表达,并可能经MyD88非依赖性信号通路引起免疫炎症反应,导致髋关节破坏.     

幽门螺杆菌致病机制的研究进展

大量研究证实 ,幽门螺杆菌 (Hp)感染是慢性胃炎和消化性溃疡的主要病因 ,并与胃腺癌、胃MALT淋巴瘤的发生密切相关。随着Hp病因重要性的增加 ,目前有很多研究致力于Hp的致病因子及发病机制 ,本文就这方面的研究进展作一简要综述。1　Hp的定值Hp必须首先定植于人胃粘膜才能进一步发挥其致病作用 ,而人胃内的pH值 ( <2 )及胃的蠕动推进作用均不利于一般细菌在胃粘膜表面停留 ,但Hp却能特异地定植于胃粘膜表面 ,引起寄居部位各种不同程度的病理变化 ,这与Hp产生的多种毒力因子有关 ,使其Hp具有以下特性。1 1　运动性 :Hp菌体呈螺旋状 ,其…     

Toll样受体2和4在老年慢性左心力衰竭中的表达

目的探讨Toll样受体2(TLR2)和T0ll样受体4(TLR4)在老年慢性左心力衰竭患者外周血单核细胞表面的表达。方法根据NYHA心功能分级和左室射血分数(LVEF)将健康对照者和慢性左心力衰竭患者分成对照组、心功能I级、Ⅱ级、Ⅲ级和Ⅳ级组。采用流式细胞仪检测外周血单核细胞表面TLR2和TLR4的表达。结果左心力衰竭患者不同心功能组中TLR2和TLR4的表达均显著高于对照组(均P<0.05),且随着心功能分级的升高而明显上升。LVEF随着心功能分级的升高而逐渐下降,且与对照组比较,均P<0.05。结论 TLR2和TLR4可能作为一种危险因素参与老年慢性左心力衰竭的发生发展。     

Toll样受体10基因启动子区rs10004195基因多态性与幽门螺杆菌感染的相关性分析

目的探讨Toll样受体10(TLR-10)基因启动子区rs10004195基因多态性与幽门螺杆菌(H.pylori)感染的相关性。方法选取13C-尿素呼气试验确诊的H.pylori阳性201例与阴性182例,用测序方法检测TLR10启动子区rs10004195基因型。结果病例rs10004195基因型分布符合Hardy-Weinberg平衡(P0.05)。H.pylori阳性组AA基因型频率(26.9%)明显高于H.pylori阴性组(18.1%)(χ2=4.150,P0.05,OR=1.66,95%CI:1.02~2.71)。结论 TLR10启动子区rs10004195基因多态性与H.pylori的易感性有关,AA基因型者易感染H.pylori。     

Toll样受体-4、9基因多态性与胃癌发病风险的相关性研究

目的研究Toll样受体(TLR)-4、TLR-9基因多态性与胃癌发病风险的相关性。方法选取2016年1月至2019年12月招募江苏省无锡市及安徽省宣城市325例胃癌患者(病例组)及同期招募该地区经体检检测结果为健康且自述无消化道疾病史的人群402例(对照组)作为研究对象,TLR-4、TLR-9基因多态性分析采用Mass-array基因芯片分析,幽门螺杆菌(Hp)感染检测采用免疫胶体金法检测抗体。结果病例组中吸烟、饮酒比例高于对照组,差异有统计学意义(P0.05)。TLR-9 rs187084基因多态性位点的GA、GA/GG基因型与胃癌发病风险相关。年龄60岁胃癌患者的TLR-9 rs187084基因多态性位点的GA及GA/GG基因型均与胃癌发病风险相关(P0.05)。非贲门部位的胃癌患者TLR-9 rs187084基因多态性位点的GA及GA/GG基因型均与胃癌发病风险相关(P0.05)。结论年龄60岁及非贲门部位胃癌患者TLR-9 rs187084基因多态性位点的GA及GA/GG基因型均与胃癌发病风险相关。     

消化性溃疡幽门螺杆菌感染与Toll样受体4基因多态性的相关性研究

HP感染是引起人类慢性胃炎、消化性溃疡及胃癌等疾病的病因之一，但研究发现在HP感染者中仅有极少数会发生上述疾病。HP致病机制与细菌数量、毒力以及环境因素、宿主易感性、胃肠黏膜内环境等有关。人类TLR4通过识别病原相关分子构型（PAMPs），激活先天性免疫应答机制，同时还诱导共刺激分子CD80的表达，     

Toll样受体4在免疫相关细胞中的作用

Toll样受体(TLRs)是参与固有免疫的重要蛋白分子,也是连接固有免疫和适应性免疫的桥梁。TLR4是TLRs家族的重要成员之一。TLR4通过调控中性粒细胞和单核巨噬细胞的活化,可促进细胞因子的释放,启动固有免疫应答。同时TLR4能促进树突状细胞的成熟,激活初始T细胞,启动适应性免疫应答。在T细胞和B细胞的适应性免疫应答中,TLR4可促进细胞分泌细胞因子,介导全身炎症反应,并调控记忆性细胞的生成。本文就TLR4在中性粒细胞、树突状细胞、单核巨噬细胞、T淋巴细胞和B淋巴细胞中的作用进行综述。     

树突细胞及其Toll样受体4在特发性血小板减少性紫癜发病中的作用

目的 研究特发性血小板减少性紫癜(ITP)患者树突细胞(DC)免疫表型及其Toll样受体4(TLR4)的表达,探讨其在ITP发病机制中的作用.方法 取ITP完全缓解患者及未达完全缓解患者治疗前后及正常人外周血,分离单个核细胞,加入细胞因子rhGM-CSF及rhIL-4诱导DC,用流式细胞术检测DC表型;酶联免疫吸附法检测DC培养上清液中IL-12p70.应用RT-PCR检测DC的TLR4表达.结果 21例ITP完全缓解患者治疗前DC的CD80和CD86阳性表达率分别为(51.60±13.47)%和(61.50±15.93)%,15例未达完全缓解者CD80和CD86分别为(53.29±19.49)%和(62.91±18.43)%,均高于正常对照的(36.03±15.43)%和(40.28±11.49)%(P＜0.01).治疗后ITP缓解患者组CD80和CD86表达率分别降为(36.48±15.19)%和(44.05±17.70)%,与治疗前比较差异有统计学意义(P＜0.01),与对照组相比差异无统计学意义(P＞0.05);未完全缓解组CD80和CD86分别降为(52.30±20.98)%和(49.79±20.28)%,但与治疗前相比差异均无统计学意义(P＞0.05),CD80仍高于正常对照组(P＜0.05),而CD86与对照组比较差异亦无统计学意义(P＞0.05).地塞米松(DXM)治疗缓解组患者治疗前DC培养上清IL-12p70为(67.52±14.43)pg/ml,明显高于正常对照的(39.78±10.03)pg/ml(P＜0.01),治疗后IL-12 p70的表达降至(43.90±8.49)pg/ml,与治疗前比较差异有统计学意义(P＜0.01),与正常对照组相比无明显差异;而未缓解组患者DC培养上清IL-12p70则由治疗前的(65.35±12.52)pg/ml降至(48.45±9.68)pg/ml(P＜0.01),但仍高于正常对照(P＜0.05).治疗缓解组ITP患者DC的TLR4 mRNA相对表达水平为0.69±0.17,明显高于正常对照组的0.31±0.09(P＜0.01),治疗后ITP患者DC的TLR4 mRNA相对表达水平降为0.35±0.11(P＜0.01),与正常对照组相比无明显差别;未缓解组DC的TLR4 mRNA相对表达水平由治疗前的0.65±0.09降至治疗后的0.52±0.21(P＜0.01),但后者仍高于正常对照组(P＜0.01).结论 DC可能通过其Toll样受体及细胞因子的分泌在ITP发病中起重要作用.     

Helicobacter pylori infection in Finland

Helicobacter pylori causes chronic gastritis worldwide and it is the most important single factor in peptic ulcer disease. Up to half of H. pylori infected individuals develop atrophic gastritis over years and decades. H. pylori infection has also been classified as a class I carcinogen in human gastric cancer. Most infections are obtained in childhood, in Finland mainly before the age of 7 years but the exact transmission routes are not known. The infection shows an age-dependent pattern, the infection being rare among children but gradually becoming more prevalent among older age groups. As new infections are few in adults and the infection only rarely disappears without effective anti-microbial therapy, the occurrence of the infection in the old actually reflects the prevalence of the infection in their childhood. In developed countries, such as Finland, a rapid decline of H. pylori prevalence rate has been demonstrated. In order to speed up this natural decline of the infection, a unique population based 'screen and treat' project was started in Vammala, a semiurban south-western community in Finland. In this survey, young inhabitants were offered diagnosis and treatment for H. pylori.     

Helicobacter pylori infection in Finland

Helicobacter pylori causes chronic gastritis worldwide and it is the most important single factor in peptic ulcer disease. Up to half of H. pylori infected individuals develop atrophic gastritis over years and decades. H. pylori infection has also been classified as a class I carcinogen in human gastric cancer. Most infections are obtained in childhood, in Finland mainly before the age of 7 years but the exact transmission routes are not known. The infection shows an age‐dependent pattern, the infection being rare among children but gradually becoming more prevalent among older age groups. As new infections are few in adults and the infection only rarely disappears without effective antimicrobial therapy, the occurrence of the infection in the old actually reflects the prevalence of the infection in their childhood. In developed countries, such as Finland, a rapid decline of H. pylori prevalence rate has been demonstrated. In order to speed up this natural decline of the infection, a unique population based ‘screen and treat’ project was started in Vammala, a semiurban south‐western community in Finland. In this survey, young inhabitants were offered diagnosis and treatment for H. pylori.     

Management of Helicobacter pylori infection

Helicobacter pylori is the cause of peptic ulcer, gastric cancer and gastric lymphoma. Diagnosis of H. pylori infection can be made using invasive and noninvasive tests. Invasive tests based on endoscopy, such as histology, are recommended when a gastric malignancy is suspected. Alternatively, noninvasive tests, such as the urea breath test and stool tests are useful for H. pylori diagnosis and follow-up. Triple therapy with either amoxicillin or metronidazole, clarithromycin and proton pump inhibitor given twice daily for 7–14 days is the recommended first-line treatment, after having checked the individual clarithromycin antimicrobial susceptibility. A triple therapy with levofloxacin, amoxicillin and proton pump inhibitor for 10–14 days should be used as second-line treatment, where the strains are susceptible to fluoroquinolone. Alternatively, bismuth-based quadruple therapy is recommended.     

Management of Helicobacter pylori infection

Helicobacter pylori is the cause of most peptic ulcer disease and a primary risk factor for gastric cancer. Eradication of the organism results in ulcer healing and reduces the risk of ulcer recurrence and complications. Testing and treatment have no clear value in patients with documented nonulcer dyspepsia; however, a test-and-treat strategy is recommended but for patients with undifferentiated dyspepsia who have not undergone endoscopy. In the office setting, initial serology testing is practical and affordable, with endoscopy reserved for use in patients with alarm symptoms for ulcer complications or cancer, or those who do not respond to treatment. Treatment involves 10- to 14-day multidrug regimens including antibiotics and acid suppressants, combined with education about avoidance of other ulcer-causing factors and the need for close follow-up. Follow-up testing (i.e., urea breath or stool antigen test) is recommended for patients who do not respond to therapy or those with a history of ulcer complications or cancer.