关键词： 活性改变   炎症状态   混合功能氧化酶   CYP450   CYP1A2   基因家族   环境致癌物   亚铁血红素  

摘要： 肝脏细胞色素P450（cytochromeP450，CYP450）氧化酶又称混合功能氧化酶和单加氧酶，广泛存在于动物、植物、微生物的各种组织中，是负责大多数临床药物、环境致癌物、外源毒物及内源活性物质生物转化的主要酶系统，具有重要的药理、生理及病理学意义。CYP450是一类亚铁血红素一硫醇盐蛋白的基因超家族，由不同的基因家族和亚家族组成，其中与药物代谢关系最为密切的主要有CYP1A2、

关键词： 慢性心力衰竭   炎症状态   毛冬青  

摘要： 目的观察毛冬青对SD大鼠慢性心力衰竭(CHF)炎症相关因子及心功能的影响。方法将60只雄性SD大鼠随机分为模型组和假手术组,模型组50只,假手术组10只。结扎腹主动脉建立CHF模型,将模型复制成功的大鼠随机分为4组:毛冬青低剂量组,毛冬青高剂量组,卡托普利组和模型组。分别给予毛冬青、卡托普利或生理盐水灌胃,2周后行经胸超声心动图检测,测定血清白介素-1β(IL-1β)和核因子κB(NF-κB)。结果毛冬青高、低剂量组CHF大鼠血清IL-1β、NF-κB水平明显低于模型组,差异有统计学意义(P<0.05)。心脏彩超显示:毛冬青高、低剂量组大鼠提高射血分数(EF)和短轴缩短率(FS)与模型组比较差异有统计学意义(P<0.05)。结论毛冬青可以改善慢性心力衰竭的炎症状态和心功能。

关键词： Epidemiology   Hearing   Inflammation   Hearing loss   Sensory  

摘要： Background. Although research has linked systemic inflammation to various diseases of aging, few studies have examined the potential role it may play in the development of age-related hearing impairment. Methods. Among 1,073 participants free of hearing impairment (pure-tone average 0.5, 1, 2, 4 kHz <= 25 dB HL) in the population-based Epidemiology of Hearing Loss Study (1998-2000), serum C-reactive protein, and interleukin-6 were measured at three time points (1988-1990, 1998-2000, and 2009-2010), and tumor necrosis factor-alpha was measured at one time point (1998-2000), whereas hearing impairment was measured again in 2003-2005 and 2009-2010 to determine the 10-year cumulative incidence. Results. Inflammatory marker levels from a single time point (1998-2000) were not associated with an increased risk of developing hearing impairment. Associations between long-term serum C-reactive protein levels and incident hearing impairment differed by age (p =.031). Participants less than 60 years with consistently high (>3 mg/L) or increasing levels of serum C-reactive protein over 10 years were nearly two times (hazard ratio: 1.96, 95% confidence interval: 1.19, 3.23) as likely to develop hearing impairment over the subsequent 10-year period, an association not seen in participants more than or equal to 60 years. A statistically significant association (p-trend =.041) was also observed between number of markers in the highest group at baseline and incident hearing impairment in this younger age group. Conclusions. Associations between long-term serum C-reactive protein levels and incident hearing impairment were observed in the cohort as a whole, but differed significantly by age group, with statistically significant associations observed in adults less than 60 years, participants moving through the peak risk period for hearing impairment over the course of the study.

关键词： Inflammation   L-NAME   obesity   vascular function  

摘要： We tested the hypothesis that a decrease in bioavailability of nitric oxide (NO) would result in increased adipose tissue (AT) inflammation. In particular, we utilized the obese Otsuka Long Evans Tokushima Fatty rat model (n = 20) and lean Long Evans Tokushima Otsuka counterparts (n = 20) to determine the extent to which chronic inhibition of NO synthase (NOS) with Nx-nitro-L-arginine methyl ester (L-NAME) treatment (for 4 weeks) upregulates expression of inflammatory genes and markers of immune cell infiltration in retroperitoneal white AT, subscapular brown AT, periaortic AT as well as in its contiguous aorta free of perivascular AT. As expected, relative to lean rats (% body fat = 13.5 +/- 0.7), obese rats (% body fat = 27.2 +/- 0.8) were hyperlipidemic (total cholesterol 77.0 +/- 2.1 vs. 101.0 +/- 3.3 mg/dL), hyperleptinemic (5.3 +/- 0.9 vs. 191.9 +/- 59.9 pg/mL), and insulin-resistant (higher HOMA IR index [3.9 +/- 0.8 vs. 25.2 +/- 4.1]). Obese rats also exhibited increased expression of proinflammatory genes in perivascular, visceral, and brown ATs. L-NAME treatment produced a small but statistically significant decrease in percent body fat (24.6 +/- 0.9 vs. 27.2 +/- 0.8%) and HOMA IR index (16.9 +/- 2.3 vs. 25.2 +/- 4.1) in obese rats. Further, contrary to our hypothesis, we found that expression of inflammatory genes in all AT depots examined were generally unaltered with L-NAME treatment in both lean and obese rats. This was in contrast with the observation that L-NAME produced a significant upregulation of inflammatory and proatherogenic genes in the aorta. Collectively, these findings suggest that chronic NOS inhibition alters transcriptional regulation of proinflammatory genes to a greater extent in the aortic wall compared to its adjacent perivascular AT, or visceral white and subscapular brown AT depots.

关键词： ovarian cancer   malnutrition   rapid turnover protein   inflammation   cachexia   interleukin-17  

摘要： Poor nutritional status is common in ovarian cancer. It is well known that the nutritional status of a patient with malignant disease is associated with survival, and that it can be assessed by serum levels of rapid turnover proteins (RTPs), such as retinol binding protein, prealbumin and transferrin. Systemic inflammation, usually observed in the form of elevated C-reactive protein (CRP) or neutrophil/lymphocyte ratio (NLR), occurs by various mechanisms involving numerous pro-inflammatory cytokines. These include interleukin (IL)-17 and other soluble protein mediators, such as soluble IL-2 receptor (sIL-2R) and vascular endothelial growth factor (VEGF). In this study, circulating levels of RTP were decreased in advanced stages of ovarian cancer, and significant inverse correlations were found between RTP levels and serum levels of CRP or NLR. CRP levels were also correlated with serum levels of VEGF and sIL-2R. Moreover, NLR, VEGF and sIL-2R levels, and IL-17 production, were all inversely correlated with RTP levels. These findings indicate that chronic inflammation may be associated with compromised immune function, such as an impaired T-cell response, via various inflammatory proteins, including sIL-2R, VEGF and IL-17. The key mechanisms leading to cancer cachexia, in which nutritional impairment is a major clinical issue, appear to be primarily immune reactions caused by chronic inflammation. Anti-inflammatory treatments may be effective in clinically improving various symptoms associated with these mechanisms.

关键词： 替米沙坦   腹膜透析   微炎症状态  

摘要： 目的观察替米沙坦对持续性非卧床腹膜透析(CAPD)患者血中炎症因子及生化指标的影响。方法选择CAPD患者64例,均服用替米沙坦治疗,观察用药前及治疗8、16周后血中超敏C-反应蛋白(hs-CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、转铁蛋白(TF)、白蛋白(Alb)、尿素氮(BUN)、肌酐(Cre)的变化。结果经替米沙坦治疗8、16周后血清hs-CRP、IL-6、TNF-a水平较治疗前降低(P<0.05、P<0.01);治疗16周后TF、Alb较治疗前增高(P<0.05);治疗后血清BUN及Scr水平与治疗前比较无统计学差异(P>0.05)。结论替米沙坦治疗后患者体内的炎症因子和营养指标均得到了明显的改善,这种改善随治疗时间延长而愈加明显。

关键词： 免疫细胞   运动行为特征   炎症反应   光学成像技术  

摘要： 物理创伤、化学损伤和病原物侵袭均能够引发机体的炎症反应。光学成像技术已逐渐用于炎症反应的活体研究。光学成像技术具有高时空分辨率的特点，可以直观可视化地研究炎症微环境中免疫细胞的聚集、吞噬、凋亡及细胞接触等过程。中性粒细胞、单核巨噬细胞（MMs）和树突细胞（DC）等免疫细胞在炎症反应中发挥重要的抗原吞噬和抗原提呈作用，但是，这些免疫细胞在炎症反应中的运动行为特征仍不完全清楚，尤其缺乏同时对多种免疫细胞进行长时程活体非侵入式监测所获得的时空动态信息。因此，本研究利用足垫和淋巴结外植体成像模型，对中性粒细胞、MMs细胞和DC细胞在卵清蛋白（OVA）诱导的迟发型超敏反应（DTH）和细菌炎症反应中的时空动态运动行为特征进行了阐释。本研究一方面从运动学角度深入了解了免疫细胞在炎症反应中的功能，另一方面从免疫细胞运动的角度展示了雷帕霉素（Rapamycin/RAPA）在抗炎作用中的免疫抑制效应。\n 主要结果如下：\n 1）建立了用于研究炎症反应中免疫细胞运动行为特征的活体多层次光学成像方法。运用整体荧光成像技术动态监测免疫细胞的聚集，采用大视野扫描显微成像技术研究免疫细胞的动态分布，同时通过共聚焦时实扫描成像来获得免疫细胞的动态信息。\n 2）运用活体光学成像技术研究了雷帕霉素对DTH的免疫抑制效果。结果显示，在炎症反应的触发阶段，中性粒细胞和MMs细胞在抗原刺激后的24 h明显聚集。雷帕霉素给药处理的炎症反应中，抗原刺激后4h雷帕霉素促进了中性粒细胞的聚集并增加了血管的通透性；抗原刺激后48 h中性粒细胞在炎症部位的聚集明显受到抑制（抑制率>50％），同时推迟了MMs细胞在炎症部位的募集。雷帕霉素处理的炎症反应中，抗原刺激后4 h免疫细胞的运动特征同其在DTH反应抗原刺激后24 h的运动特征类似，这些运动参数包括免疫细胞的平均运动速度、滞留时间、平均位移和限制性系数等。结合对细胞因子的检测结果，可以推测雷帕霉素缩短了DTH反应的准备阶段，同时减弱了反应期的反应强度，这一过程可能涉及T辅助2型细胞（Th2）或调节性T细胞（Treg）。\n 3）研究了雷帕霉素对DC表型和功能的调节作用。研究结果表明，雷帕霉素减小了DC细胞的体积，显著降低了共刺激分子CD80的表达；抑制了DC细胞的抗原吞噬能力和DC细胞刺激作用下抗原特异性或非特异性淋巴细胞的增殖能力，停止雷帕霉素药物处理一段时间后这种抑制效果可以被逆转。此外，雷帕霉素明显缩短了DC与T细胞长时间接触（>15分钟）的比率，该比率的降低在雷帕霉素抑制DTH反应中发挥着重要作用。\n 4）建立了研究足垫细菌炎症反应的非侵入性三色成像模型，可对细菌、中性粒细胞和 MMs细胞进行同步成像。研究发现，诱发炎症反应的大肠杆菌（***）三天内大大减少；中性粒细胞在细菌刺激后4 h迅速聚集，4-24 h运动活跃，48-72 h运动能力减弱，并出现大量的细胞碎片。同时，MMs细胞在炎症反应后24 h到72h大量聚集，但此时其运动速度减慢、滞留时间增加、运动范围缩小。此外，吞噬了细菌的MMs细胞，在快速运动时发生了细胞结构的解体。这些结果进一步揭示了机体免疫系统抵抗病原物的动态行为变化。\n 综上所述，本研究建立了用于免疫细胞动态特征研究的多层次光学成像方法，并成功获取炎症反应过程免疫细胞的聚集、分布、迁移和接触等动态信息。雷帕霉素对免疫细胞运动特征的影响，揭示了其可能的抗炎机制。此外，本研究还建立了用于细菌炎症反应研究的非侵入式三色成像模型。本研究所建立的活体免疫光学成像技术可以从组织水平到细胞水平对多种免疫细胞在免疫反应中的动态变化进行观测。利用免疫光学成像技术对雷帕霉素抗炎作用的深入探讨说明这些技术可以应用于更多的免疫反应研究和免疫治疗效应评价。

关键词： 益气通瘀法   全身炎症反应   凝血功能   多器官功能障碍综合征  

摘要： 目的观察益气通瘀法对多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)患者全身炎症反应和凝血功能的影响。方法将2010年5月—2011年12月南京中医药大学附属医院收治的符合MODS诊断标准的40例患者随机分为对照组(19例)及试验组(21例),对照组给予西医常规治疗,试验组在对照组治疗基础上给予益气通瘀汤药,观察两组患者用药前、用药后第3、7、14天的炎症反应和凝血功能。结果用药后第7天,试验组IL-1、IL-6、PT水平较同期对照组降低(P<0.05);第14天,试验组TNF-α及D-二聚体(D-dimer,DD)水平较同期对照组降低(P<0.05)。两组APTT及纤维蛋白质(fibrinogen,FIB)治疗后第3、7、14天比较差异均有统计学意义(P>0.05)。结论益气通瘀法可减轻患者的全身炎症反应,改善外源性凝血功能。

关键词： 社区获得性感染   肺炎   全身炎症反应综合征   N-末端脑钠肽前体  

摘要： 目的探讨社区获得性肺炎(CAP)合并与未合并全身炎症反应综合征(SIRS)患者N-末端脑钠肽前体(NT-proBNP)水平变化及临床意义。方法选择2012年1月—2013年3月我院住院的CAP患者148例,依据是否合并SIRS分为CAP非SIRS组78例和CAP合并SIRS组70例。采用酶联免疫吸附法测定两组患者的血清NT-proBNP水平,并行肺炎严重指数(PSI)评分。结果 CAP合并SIRS组NT-proBNP水平较CAP非SIRS组升高〔188.0(471.8)和62.5(135.3),P=0.009〕。CAP患者NT-proBNP水平与PSI评分呈正相关(r=0.292,P=0.001)。结论 CAP合并SIRS患者NT-proBNP水平升高,依据NT-proBNP水平可区分CAP是否合并SIRS,并可作为CAP患者病情严重程度及预后的判断指标。

关键词： 连续性血液净化   一氧化氮合酶   降钙素   原   全身炎症反应综合征   脓毒血症  

摘要： 目的:研究连续性血液净化(CRRT)对治疗全身炎症反应综合征(SIRS)及脓毒血症(Sepsis)的临床疗效及对患者一氧化氮合酶(NOS)和降钙素原(PCT)的影响,为CRRT和SIRS治疗提供新思路。方法:收集收住本院急诊ICU、内科ICU及外科ICU的SIRS及Sepsis患者病例,记录在血液净化治疗前及治疗后24、48、72h的生命体征、氧合指数(PaO2/FiO2)、血生化、血常规、血气分析、APACHE II评分的变化,并采用比色法检测患者血清NOS含量变化,采用免疫发光法检测患者血清PCT含量变化。结果:CRRT治疗后24、48、72h血生化及血常规指标均有显著改善,各时间点NOS值及PCT值较治疗前均显著降低,差异具有统计学意义(P<0.05)。结论:CRRT治疗能显著改善SIRS/Sepsis患者的临床症状,其治疗作用与清除损伤性作用因子NOS及PCT相关。