七氟醚预处理对全身缺氧损伤小鼠脑NO含量和NOS活性的影响

目的观察七氟醚(Sev)预处理后全身缺氧损伤小鼠的生存状况,测定脑内一氧化氮(NO)含量及一氧化氮合酶(NOS)活性,探讨七氟醚预处理的保护作用。方法 6~7周龄健康雄性昆明小鼠120只,随机分为3组:Sev 0.5 h组、Sev 24 h组及对照组(P组),每组40只。Sev 0.5 h组吸入1.0%Sev 30 min,在空气中洗脱30 min后放入体积分数5%O2+95%N2环境中持续20 min;Sev 24 h组每天吸入体积分数1.0%Sev30 min,连续2 d,第3天放入体积分数5%O2+95%N2环境中持续20 min;P组不吸入Sev,直接放入体积分数5%O2+95%N2环境中持续20 min。观察小鼠在体积分数5%O2环境中20 min内的生存时间、生存率,测定脑组织NO含量和NOS活性。结果与P组比较,Sev 0.5 h组小鼠生存率提高、生存时间延长(P<0.05),脑组织NO含量降低,NOS活性增高(P<0.05);而Sev 24 h组与P组比较差异无统计学意义(P>0.05)。Sev 0.5 h组与Sev 24 h组比较,生存率提高,生存时间延长(P<0.05),NO含量和NOS活性差异有统计学意义(P<0.05)。结论 Sev预处理能对全身缺氧损伤小鼠产生保护作用,通过即刻效应提高小鼠在低氧环境中的生存率,延长其生存时间,降低脑组织中的NO含量,提高NOS活性,减轻脑组织缺氧损伤。     

海参岩藻聚糖硫酸酯对巨噬细胞的调节作用及信号通路研究

目的研究海参岩藻聚糖硫酸酯(SC-FUC)对巨噬细胞的调节作用及相关信号通路,探究其调节机体免疫的作用机制。方法噻唑蓝(MTT)比色法检测巨噬细胞的增殖情况;中性红法检测吞噬活性;Griess试剂法测定培养上清液中NO含量;RT-PCR检测巨噬细胞下游细胞因子IL-6、IL-10、Toll样受体和相关信号分子My D88、TRIF、NF-κB的mRNA表达量。结果 SC-FUC对巨噬细胞增殖、吞噬能力和NO分泌均有促进作用,在作用前期(6h和12h)效果更为明显。SC-FUC能上调细胞因子IL-6和IL-10的mRNA表达量,上调TLR4、TLR5、TLR9的表达量,促进信号分子My D88、TRIF和NF-κB的mRNA表达量。结论 SC-FUC能够激活巨噬细胞,促进其分泌NO、IL-6、IL-10等细胞因子,从而发挥免疫调节作用。SC-FUC激活巨噬细胞的信号通路与细胞表面TLR4、TLR5、TLR9及NF-κB通路相关。     

多巴胺联合西地那非治疗新生儿肺动脉高压的临床研究

目的 探讨多巴胺联合西地那非治疗新生儿肺动脉高压的临床疗效.方法 选取2011年6月—2014年11月天津市西青医院收治的肺动脉高压患儿90例,随机分为对照组和治疗组,每组45例.对照组患儿口服或鼻饲枸橼酸西地那非片0.5~1.0 mg/(kg·次),1次/6 h.治疗组患儿在对照组治疗的基础上,静脉滴注盐酸多巴胺注射液5μg/(kg·min),输液泵持续静脉滴入.两组均连续治疗3 d.观察两组患者的临床疗效,同时比较两组治疗前后动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、肺动脉压(PAP)、动脉血氧饱和度(SaO2)、血清内皮素(ET-1)、缺氧诱导因子(HIF-1α)、一氧化氮(NO)、促红细胞生成素(EPO)、Ca2+的变化.结果 治疗后,对照组和治疗组总有效率分别为82.22%、95.56%,两组总有效率比较差异具有统计学意义(P<0.05).两组PaO2、SaO2、NO均较治疗前显著升高,PaCO2、PAP、EPO、HIF-1、ET-1较治疗前显著降低,同组治疗前后差异有统计学意义(P<0.01);治疗组这些观察指标的改善程度优于对照组,两组比较差异有统计学意义(P<0.05).两组Ca2+均较治疗前显著升高(P<0.05),但两组比较差异无统计学意义.结论 多巴胺联合西地那非治疗新生儿肺动脉高压具有较好的临床疗效,可显著调节缺氧相关因子水平,值得临床推广应用.     

复方田七胃痛片联合四联疗法治疗难治性消化性溃疡的临床研究

目的探讨复方田七胃痛片联合以埃索美拉唑镁肠溶片为基础的四联疗法治疗难治性消化性溃疡的临床疗效。方法选择2013年3月—2015年3月辽宁省人民医院消化内科收治的消化性溃疡患者149例,随机分为对照组(75例)和治疗组(74例)。对照组口服埃索美拉唑镁肠溶片20 mg/次,2次/d;果胶铋胶囊3粒/次,3次/d;克拉霉素片0.5 g/次,2次/d;阿莫西林胶囊1 g/次,2次/d。治疗组在对照组的基础上口服复方田七胃痛片4片/次,3次/d。8周后评价疗效。比较临床疗效、镜下疗效、幽门螺杆菌的消除情况以及胃窦黏膜一氧化氮(NO)和内皮素(ET)水平。结果治疗组临床疗效的有效率、显效率分别为97.30%、86.49%,对照组的有效率、显效率分别为85.33%、66.67%,两组比较的差异具有统计学意义(P0.05)。治疗组的镜下疗效有效率为98.65%,高于对照组(90.67%),两组比较差异具有统计学意义(P0.05)。治疗组的根除率(91.89%)高于对照组(76.00%),两组比较差异具有统计学意义(P0.05)。治疗后两组NO水平升高,ET水平下降,与治疗前比较差异均具有统计学意义(P0.01);与对照组比较,治疗组NO水平上升,ET水平下降,两组差异具有统计学意义(P0.01)。结论复方田七胃痛片联合以埃索美拉唑镁肠溶片为基础的四联疗法具有较好的临床疗效,加快溃疡愈合,消除幽门螺杆菌,其机制可能与提高胃窦黏膜NO水平、降低ET水平有关。     

冠心病患者周围血一氧化氮、肿瘤坏死因子变化的意义及开搏通的影响

本文通过对４８例冠心病（ＣＨＤ）患者外周血一氧化氮（ＮＯ）、肿瘤坏死因子（ＴＮＦ）的测定及开搏通治疗前后的对比，结果显示：ＣＨＤ患者周围血ＮＯ明显降低（Ｐ＜０．０１），ＴＮＦ显著高于正常（Ｐ＜００１），且与病情严重程度相一致，接受开搏通治疗三周后，ＮＯ有所回升，ＴＮＦ明显下降，治疗前后比较有显著差异（Ｐ＜００１），提示ＮＯ，ＴＮＦ参与ＣＨＤ的发病过程开搏通具有治疗意义。     

诱癌过程中鼠肝组织一氧化氮合酶的表达与改变

目的：研究ＮＯ合酶在肝癌发生过程中的表达与改变。方法：以化学致癌剂２－ＦＡＡ喂饲ＳＤ大鼠，对鼠肝细胞在癌变过程中的组织学改变、一氧化氮合酶（ＮＯＳ）的表达和动态变化进行了研究。结果：当肝细胞轻度损伤时，肝组织中ＮＯＳ活性与对照组相比明显下降；当肝细胞表现为癌前病变和肝细胞完全癌变时，肝组织中ＮＯＳ的合成增加其比活性仍低于正常对照鼠；肝组织中ＮＯＳ与ＮＯ水平呈明显正相关（ｒ＝０５７，Ｐ＜００１），而与总ＲＮＡ浓度无相关性。结论：研究资料提示ＮＯＳ在诱癌早期的表达处于抑制状态以对肝细胞起保护作用；而肝癌形成阶段，ＮＯＳ加速表达以杀伤肿瘤细胞     

阻塞性睡眠呼吸暂停低通气综合征患者血浆ET-1、NO水平的变化及nCPAP对其影响

目的　观察阻塞性睡眠呼吸暂停低通气综合征 (OSAHS)患者经鼻持续气道内正压通气 (nCPAP)治疗前后血浆ET 1、NO水平的变化 ,并探讨其临床意义。方法　选择OSAHS无EH者 (A组 ) ,OSAHS合并EH者 (B组 ) ,正常对照 (C组 ) ,三组行PSG监测。用放免法测血浆ET 1 ,NO采用硝酸还原酶法。A、B两组施以nCPAP治疗。用袖带加压法观察血压。结果　①与C组相比 ,A组AHI、ET 1 /NO增高 ,最低SaO2 下降 ,治疗后情况相反 ;A组治疗前后ET 1 /NO分别与AHI、最低SaO2 均明显相关 (r分别为 0 40 8、- 0 569)。②与C组相比 ,B组MBP、AHI、ET 1 /NO增高 ,最低SaO2 下降 ,治疗后情况相反 ;B组治疗前后MBP分别与ET 1 /NO、AHI、最低SaO2 均明显相关 ,r分别为 0 439、0 51 5、- 0 455。结论　①OSAHS可引起血压升高 ,某些血管舒缩因子比例失衡可能在OSAHS合并EH中起一定的病理作用 ;②nCPAP对治疗OSAHS合并EH及预防OSAHS高的心脑血管并发症均有益处     

Relative contribution of different l-arginine sources to the substrate supply of endothelial nitric oxide synthase

In certain cases of endothelial dysfunction l-arginine becomes rate-limiting for NO synthesis in spite of sufficiently high plasma concentrations of the amino acid. To better understand this phenomenon, we investigated routes of substrate supply to endothelial nitric oxide synthase (eNOS). Our previous data with human umbilical vein (HUVEC) and EA.hy.926 endothelial cells demonstrated that eNOS can obtain its substrate from the conversion of l-citrulline to l-arginine and from protein breakdown. In the present study, we determined the quantitative contribution of proteasomal and lysosomal protein degradation and investigated to what extent extracellular peptides and l-citrulline can provide substrate to eNOS. The RFL-6 reporter cell assay was used to measure eNOS activity in human EA.hy926 endothelial cells. Individual proteasome and lysosome inhibition reduced eNOS activity in EA.hy926 cells only slightly. However, the combined inhibition had a pronounced reducing effect. eNOS activity was fully restored by supplementing either l-citrulline or l-arginine-containing dipeptides. Histidine prevented the restoration of eNOS activity by the dipeptide, suggesting that a transporter accepting both, peptides and histidine, mediates the uptake of the extracellular peptide. In fact, the peptide and histidine transporter PHT1 was expressed in EA.hy926 cells and HUVECs (qRT/PCR). Our study thus demonstrates that l-citrulline and l-arginine-containing peptides derived from either intracellular protein breakdown or from the extracellular space seem to be good substrate sources for eNOS.     

Immunology of Helicobacter pylori: insights into the failure of the immune response and perspectives on vaccine studies

Helicobacter pylori infects the stomach of half of the human population worldwide and causes chronic active gastritis, which can lead to peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The host immune response to the infection is ineffective, because the bacterium persists and the inflammation continues for decades. Bacterial activation of epithelial cells, dendritic cells, monocytes, macrophages, and neutrophils leads to a T helper cell 1 type of adaptive response, but this remains inadequate. The host inflammatory response has a key functional role in disrupting acid homeostasis, which impacts directly on the colonization patterns of H pylori and thus the extent of gastritis. Many potential mechanisms for the failure of the host response have been postulated, and these include apoptosis of epithelial cells and macrophages, inadequate effector functions of macrophages and dendritic cells, VacA inhibition of T-cell function, and suppressive effects of regulatory T cells. Because of the extent of the disease burden, many strategies for prophylactic or therapeutic vaccines have been investigated. The goal of enhancing the host's ability to generate protective immunity has met with some success in animal models, but the efficacy of potential vaccines in humans remains to be demonstrated. Aspects of H pylori immunopathogenesis are reviewed and perspectives on the failure of the host immune response are discussed. Understanding the mechanisms of immune evasion could lead to new opportunities for enhancing eradication and prevention of infection and associated disease.