小儿幽门螺旋杆菌感染与缺铁性贫血的相关性分析

目的:分析并探讨小儿幽门螺杆菌感染与缺铁性贫血的相关性。方法:选择2012年2月至2013年2月本院门诊患儿412例,行血常规、血清铁、血清铁蛋白、HP-IgG抗体检测。结果:HP感染患儿IDA26例,IDA患病率为20.4%(26/127),HP未感染患儿IDA19例,IDA患病率为6.7%(19/285)。两者比较差异有统计学意义(x2=17.21,P=0.00)。对比两组患儿MCV、MCH、MCHC指标,差异具有显著性(P均0.05)。45例IDA患儿中26例有HP感染,感染率为57.8%(26/45),367例非IDA患儿中有101例HP感染,感染率为27.5%(101/367)。两者比较差异有统计学意义(x2=17.21,P=0.00)。结论:HP感染同IDA发病有显著相关性,HP感染可以是导致IDA的原因。     

Helicobacter pylori Infection Induces Anemia,Depletes Serum Iron Storage,and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice

Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world’s population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6–9 weeks of age, and were necropsied at 27–29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001). Infected mice had a lower red blood cell count (p<0.0001), hematocrit (p < 0.001), and hemoglobin concentration (p <0.0001) than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp) was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001). Expression of bone morphogenic protein 4 (Bmp4), a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001). Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp SS1-infected INS-GAS mice will be an appropriate animal model for further study of the effects of concurrent H. pylori infection and anemia on iron homeostasis and adult iron-dependent brain gene expression.     

幽门螺杆菌致人胃病的小鼠模型研究

目的建立幽门螺杆菌致人胃病的小鼠模型.方法用Ⅰ型幽门螺杆菌(Helicobacter pylori,Hp)对三种SPF级小鼠(BALB/c、NIH、 KM)采用循环滴喂攻击等方法处理,从菌体定值、抗体水平、病理变化三个方面分14、39、69、105 d进行测试.结果 Hp可持续定植于各供试小鼠胃粘膜上,并刺激Hp抗体(IgG)维持一较高水平,Hp在小鼠上主要引起以胃粘膜变性坏死为主,伴有淋巴细胞浸润的炎症反应,这为Hp致人胃病的症状相似.结论为Hp的致病机理,治疗药物和疫苗研究提供了良好的小动物模型.     

Helicobacter pylori Induces Inflammation in Mouse Urinary Bladder and Pelvis

Helicobacter pylori was transurethrally inoculated into the mouse urinary tract. The organism established infection and induced inflammation in the urinary bladder and pelvis. During the infection, urinary pH was elevated, probably due to the production of NH3 by bacterial urease. H. pylori was recovered from the urinary bladder, kidney and urine of the infected mice. Histopathologically, severe neutrophil infiltration was observed in the mucosal layer of both organs. H. pylori was detected on the surface of the epithelial cells. These results indicate that low pH and bacterial flora were not essential factors in establishing the mucosal infection with H. pylori. This experimental system is useful to investigate the pathogenicity of H. pylori in mucosal organs.     

Ferrous Iron Induces Nrf2 Expression in Mouse Brain Astrocytes to Prevent Neurotoxicity

Free radical damage caused by ferrous iron is involved in the pathogenesis of secondary brain injury after intracerebral hemorrhage (ICH). NF‐E2‐related factor 2 (Nrf2), a major phase II gene regulator that binds to antioxidant response element, represents an important cellular cytoprotective mechanism against oxidative damage. We hypothesized that Nrf2 might protect astrocytes from damage by Fe²⁺. Therefore, we examined cytotoxicity in primary astrocytes induced by iron overload and evaluated the effects of Fe²⁺ on Nrf2 expression. The results demonstrated that 24‐h Fe²⁺ exposure exerted time‐ and concentration‐dependent cytotoxicity in astrocytes. Furthermore, Fe²⁺ exposure in astrocytes resulted in time‐ and concentration‐dependent increases in Nrf2 expression, which preceded Fe²⁺ toxicity. Nrf2‐specific siRNA further knocked down Nrf2 levels, resulting in greater Fe²⁺‐induced astrocyte cytotoxicity. These data indicate that induction of Nrf2 expression could serve as an adaptive self‐defense mechanism, although it is insufficient to completely protect primary astrocytes from Fe²⁺‐induced neurotoxicity.     

Gastric Infection with Kazachstania heterogenica Influences the Outcome of a Helicobacter suis Infection in Mongolian Gerbils

Background:  The Mongolian gerbil model is often used to investigate the interactions between different gastric Helicobacter species and the gastric tissue. A preliminary screening of a gerbil population intended for use in Helicobacter suis infection studies revealed a natural yeast infection in the stomach of these animals. After identification, we have investigated the effect of the gastric yeast infection on the outcome of an experimental H. suis infection in Mongolian gerbils.
Materials and methods:  Yeast cells were isolated from the stomachs of Mongolian gerbils. Identification was done by Internally Transcribed rRNA Spacer 2 Region PCR fragment length analysis. To investigate a possible pathologic role of this yeast, Mongolian gerbils were infected experimentally with this yeast. Co-infection with the newly isolated H. suis was performed to investigate possible interactions between both micro-organisms.
Results:  Kazachstania heterogenica was found colonizing the stomach of Mongolian gerbils, mainly in the antrum. Few pathologic changes were seen in the stomachs of infected animals. Experimental co-infection of gerbils with this yeast and the newly isolated H. suis showed a significant increase in inflammation in animals infected with both micro-organisms compared to animals infected only with H. suis .
Conclusions:  K. heterogenica colonizes the stomach of Mongolian gerbils in exactly the same regions as gastric Helicobacter species. The uncontrolled presence of this yeast in the gerbil stomach can lead to an overestimation of the inflammation caused by Helicobacter in this animal model.     

Toxoplasma gondii Infection Induces Suppression in a Mouse Model of Allergic Airway Inflammation

Allergic asthma is an inflammatory disorder characterized by infiltration of the airway wall with inflammatory cells driven mostly by activation of Th2-lymphocytes, eosinophils and mast cells. There is a link between increased allergy and a reduction of some infections in Western countries. Epidemiological data also show that respiratory allergy is less frequent in people exposed to orofecal and foodborne microbes such as Toxoplasma gondii. We previously showed that both acute and chronic parasite T. gondii infection substantially blocked development of airway inflammation in adult BALB/c mice. Based on the high levels of IFN-γ along with the reduction of Th2 phenotype, we hypothesized that the protective effect might be related to the strong Th1 immune response elicited against the parasite. However, other mechanisms could also be implicated. The possibility that regulatory T cells inhibit allergic diseases has received growing support from both animal and human studies. Here we investigated the cellular mechanisms involved in T. gondii induced protection against allergy. Our results show for the first time that thoracic lymph node cells from mice sensitized during chronic T. gondii infection have suppressor activity. Suppression was detected both in vitro, on allergen specific T cell proliferation and in vivo, on allergic lung inflammation after adoptive transference from infected/sensitized mice to previously sensitized animals. This ability was found to be contact- independent and correlated with high levels of TGF-β and CD4(+)FoxP3(+) cells.     

Hepatitis C Virus Infection Causes Iron Deficiency in Huh7.5.1 Cells

Patients with chronic hepatitis C virus (HCV) infection frequently develop systemic iron overload, which exacerbates morbidity. Nevertheless, iron inhibits HCV replication in cell culture models and thereby exerts antiviral activity. We hypothesized that the cellular iron status is crucial for the establishment of HCV infection. We show that HCV infection of permissive Huh7.5.1 hepatoma cells promotes an iron deficient phenotype. Thus, HCV leads to increased iron regulatory protein (IRP) activity, accumulation of IRP2 and suppression of transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) in the host. These data suggest that HCV regulates cellular iron levels to bypass iron-mediated inhibition in viral replication.     

霉菌、幽门螺杆菌及双菌种感染在胃溃疡、胃癌中检出的意义

探讨霉菌、幽门螺杆菌(Hp)单菌种感染和霉菌、Hp(双菌种)同时感染在胃癌及胃溃疡中的组织病理学变化、发病情况及意义。采用常规石蜡切片,HE染色和PAS、Giemsa特殊染色、免疫组织化学染色及PCR方法,对223例慢性浅表性胃炎、111例慢性萎缩性胃炎、116例胃溃疡、121例胃癌纤维胃镜活检标本进行回顾性研究。结果显示,慢性浅表性胃炎、慢性萎缩性胃炎未检出双菌种感染。胃溃疡双菌种感染11例,检出率9.5%;胃癌双菌种感染21例,检出率17.4%。双菌种感染在胃癌及胃溃疡中的发现,表明双菌种感染可能是导致胃溃疡、胃癌发生的又一致病因素。     

胃幽门螺杆菌感染与口臭的相关性研究

目的:探讨胃幽门螺杆菌感染与口臭发生的相关性。方法:选取48例口臭患者为研究对象,另选取96例无口臭的健康志愿者为无口臭组,通过13C呼气试验检测所有研究对象幽门螺杆菌的感染情况,比较两组幽门螺杆菌的感染率。根据是否感染幽门螺杆菌分为感染组和无感染组,比较两组口臭的发生率,分析幽门螺杆菌感染与口臭发生的相关性。结果:口臭组和非口臭组患者幽门螺杆菌的感染率分别为79.17%,27.08%,口臭组显著高于无口臭组,差异有统计学意义(x2=35.16,P0.05)。口臭与幽门螺杆菌的感染显著相关(r=0.4)。幽门螺杆菌感染组患者和未感染组口臭的发生率分别为70.31%和3.75%,感染组显著高于未感染组,差异有统计学意义(x2=70.89,P0.05)。幽门螺杆菌的感染与口臭的发生率显著相关(r=0.69)。结论:幽门螺杆菌感染与口臭的发生有密切的相关性,是引起口臭的一个重要因素。     

幽门螺杆菌感染促进胃炎儿童胃粘膜细胞的增殖

本研究旨在探讨幽门螺杆菌感染对小儿慢性胃炎患者细胞增殖的影响,使用内镜检查消化不良患者的上消化道症状,使用改良的Giemsa染色检测胃粘膜活组织中幽门螺杆菌,用苏木精/曙红和改良的吉姆萨染色活组织,并通过光学显微镜研究染色后胃粘膜样品组织病理学变化,RT-PCR检测各组胃粘膜细胞中调控细胞凋亡的Bcl-2、Bcl-xl、Bax和PCNA的mRNA表达,提取胃粘膜细胞蛋白质,利用蛋白质免疫印迹分析蛋白质浓度。组织化学染色结果表明,与对照相比,患有胃炎和幽门杆菌感染后的胃炎患者胃粘膜细胞明显增加,且幽门螺杆菌感染后细胞增殖更显著(p<0.05);幽门螺杆菌感染后Bcl-2和Bcl-xl,PCNA在患者体内表达显著上调(p<0.05),而细胞促凋亡因子Bax基因在胃炎患者感染幽门螺杆菌后被显著下调(p<0.05),蛋白免疫印迹分析Bcl-2,Bcl-xl,Bax和PCNA蛋白表达趋势与基因表达一致,说明结果可靠。幽门螺杆菌感染会显著提高慢性胃炎儿童患者胃粘膜细胞的增殖。