连翘提取物和连翘挥发油对酵母致热大鼠的解热机制研究

对比观察连翘提取物和连翘挥发油对酵母菌所致发热大鼠的解热效应和机制。酵母菌皮下注射复制大鼠发热模型。测基础体温后,随机分为空白组、模型组、连翘提取物组(25生药g/kg)和连翘挥发油组(26.7生药g/kg)四组,动态观察给药后大鼠2 h体温和下丘脑c AMP和PGE2含量。结果表明连翘提取物和连翘挥发油均可显著降低酵母致热大鼠的体温(P0.01或P0.05),能显著降低下丘脑中c AMP(P0.05)含量;另外连翘提取物能显著降低下丘脑中PGE2(P0.05)含量。连翘提取物有下调下丘脑中c AMP、PGE2作用,连翘挥发油通过下调下丘脑c AMP发挥解热作用,可用于临床发热的对症治疗。     

不同大鼠模型探讨连翘挥发油解热、抗炎作用

观察连翘挥发油对不同大鼠模型的作用,探讨其解热、抗炎的作用机理。采用干酵母皮下注射和脂多糖腹腔注射建立大鼠发热模型评价连翘挥发油的解热作用,采用右后足皮下注射角叉菜胶、鸡蛋清建立大鼠足肿胀模型以及建立大鼠棉球肉芽肿模型评价其的抗炎作用。发现连翘挥发油可抑制脂多糖和干酵母所致发热,降低角叉菜胶和鸡蛋清所诱导的大鼠足肿胀,与模型组对比均有明显差异(P0.05);且可显著抑制肉芽组织的增生,与模型组对比有明显差异(P0.01)。结果表明连翘挥发油具有明显的解热、抗炎作用,为对其清热解毒作用作进一步的研究提供了一定的理论依据。     

连翘酯苷对拟AD复合动物模型小鼠学习记忆的改善作用及其机制研究

目的以β淀粉样蛋白损伤自然衰老小鼠建立一种新的复合式老年痴呆(AD)小鼠模型,观察连翘酯苷对复合模型学习记忆障碍的改善作用,并对其机制进行初步探讨。方法采用14月龄C57BL/6小鼠侧脑室注射Aβ25-35形成拟AD复合模型;Morris水迷宫实验观察小鼠学习记忆能力,实验结束取小鼠脑组织用放射免疫分析法检测TNF-α及IL-1的含量;Western blot方法检测GFAP蛋白表达,化学比色法测定ChAT、AchE、SOD酶活性及MDA的含量。结果水迷宫实验中连翘酯苷组可显著改善小鼠的学习记忆能力(P<0.05)。作用机制研究发现:连翘酯苷能降低TNF-α、IL-1的含量(P<0.05),抑制GFAP蛋白表达。提高ChAT、SOD酶活力,降低AchE活性及MDA的含量(P<0.05,P<0.01)。结论连翘酯苷对拟AD复合动物模型学习记忆的改善作用可能与抑制脑内炎症反应,调节胆碱能系统,抗氧化作用等有关。     

连翘苷降血脂及抗氧化作用的实验研究

用高脂饲料造成营养性高脂血症模型,观察连翘苷的降血脂和抗氧化作用。结果显示,与高脂血症模型组相比较,连翘苷给药组动物的血浆总胆固醇(TC)、三酰甘油(TG),低密度脂蛋白胆固醇(LDL-C)、动脉粥样硬化指数(AI)均有不同程度下降,高密度脂蛋白胆固醇(HDL-C)有所上升,血中过氧化氢酶(CAT)、过氧化物酶(POD)活性增强,血浆中丙二醛(MDA)的含量降低,说明连翘苷具有降低营养性高脂血症小鼠血脂和抗氧化的作用。     

连翘抗炎药效物质基础筛选研究

主要探索连翘几种成分的抗炎活性,并筛选其抗炎药效物质基础,为连翘抗炎新药的开发提供参考依据。建立二甲苯致小鼠耳肿胀模型,计算肿胀度。采用酶联免疫法(ELISA)测定小鼠血清中肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)的含量。对比各组的肿胀度及TNF-α和IL-6的含量。连翘苷对小鼠耳肿胀度及TNF-α和IL-6的生成无明显抑制作用,与空白组相比无显著性差异(P0.05)。连翘脂素、连翘酯苷A、连翘酯苷B均能有效抑制小鼠耳肿胀及TNF-α和IL-6的生成,与空白组相比有显著性差异(P0.05)。由此可见对所筛选的连翘4种成分,通过口服给药的方式,连翘抗炎药效物质有连翘脂素、连翘酯苷A和连翘酯苷B。通过口服给药,尚未发现连翘苷的抗炎活性,而连翘脂素、连翘酯苷A及连翘酯苷B显示较强的抗炎活性。同时推测其抗炎机制可能与抑制TNF-α和IL-6这两种炎症因子的生成和多成分作用有关。     

河南和山西连翘叶中总木脂素、连翘酯苷A、连翘酯苷B和连翘苷的含量比较北大核心CSCD

测定河南和山西连翘叶中总木脂素、连翘酯苷A、连翘酯苷B和连翘苷含量。采用分光光度法测定连翘叶中总木脂素含量,结果显示山西连翘叶高于河南连翘叶总木脂素含量。采用高效液相色谱法(HPLC)测定连翘叶中连翘酯苷A、连翘酯苷B和连翘苷的含量。连翘酯苷A平均回收率为99.6%,RSD为1.23%;连翘酯苷B平均回收率为101.3%,RSD为1.74%;连翘苷平均回收率为102.3%,RSD为2.58%;连翘叶中连翘酯苷A和连翘苷的含量较高,并且不同产地连翘叶中连翘苷含量差异较大;另外对于富含连翘酯苷和连翘苷的连翘叶能否代替果实或者与果实合并用药有待于进一步研究。     

河南和山西连翘叶中总木脂素、连翘酯苷A、连翘酯苷B和连翘苷的含量比较

测定河南和山西连翘叶中总木脂素、连翘酯苷A、连翘酯苷B和连翘苷含量。采用分光光度法测定连翘叶中总木脂素含量,结果显示山西连翘叶高于河南连翘叶总木脂素含量。采用高效液相色谱法(HPLC)测定连翘叶中连翘酯苷A、连翘酯苷B和连翘苷的含量。连翘酯苷A平均回收率为99.6%,RSD为1.23%;连翘酯苷B平均回收率为101.3%,RSD为1.74%;连翘苷平均回收率为102.3%,RSD为2.58%;连翘叶中连翘酯苷A和连翘苷的含量较高,并且不同产地连翘叶中连翘苷含量差异较大;另外对于富含连翘酯苷和连翘苷的连翘叶能否代替果实或者与果实合并用药有待于进一步研究。     

基于响应面法从连翘叶中提取连翘酯苷A和连翘苷的工艺优化

采用响应面分析法优化连翘叶中连翘酯苷A和连翘苷的最佳提取工艺条件,在单因素实验基础上,采用Box-Behnken中心组合设计原理研究液料比、乙醇浓度、浸提时间、浸提温度4个因素对连翘酯苷A得率和连翘苷得率的影响.利用Design Expert 8.0.5 b分析确定最佳提取工艺,根据实际条件,得到连翘酯苷A和连翘苷的最佳提取工艺为:乙醇浓度53％、提取温度74℃、浸提时间为53 min、液料比30 mL/g.回归模型预测最优条件下连翘酯苷A得率为7.53％,连翘苷得率为3.03％,验证值分别为7.56％,3.09％,与预测值的相对误差分别为0.4％,2.0％.     

基于人呼吸道上皮细胞炎症模型的连翘提取物抗炎活性实验研究

通过复制LPS诱导的BEAS-2B炎症模型,探讨连翘提取物对炎症反应中炎性因子分泌的作用。采用MTT法检测BEAS-2B细胞活力,筛选连翘乙醇提取物(FSEE)、60%连翘酯苷A(60%FTA)、90%连翘酯苷A(90%FTA)最佳给药浓度;采用倒置显微镜观察连翘提取物对细胞作用后的细胞形态;采用Griess Reagent法检测细胞培养上清NO含量;流式细胞术检测细胞内活性氧(ROS)的水平。毒性试验结果表明,连翘提取物浓度小于128μg/m L时,对BEAS-2B细胞没有产生毒性;浓度在128~256μg/m L时,60%FTA与90%FTA均表现出对细胞的毒性。抗炎结果表明,在给药浓度设置为25、50、100μg/m L时,三种提取物均表现出减少NO分泌的效果(P0.01),90%FTA组存在剂量依赖关系;三种提取物可显著降低LPS诱导的BEAS-2B细胞胞内活性氧的水平(P0.05),且呈量效关系。另外,FSEE、60%FTA、90%FTA组间的治疗效果也逐渐增强。由此得出,90%FTA为连翘提取物抗炎作用的主要活性部位,其抗炎活性成分可能为连翘酯苷A,这将为连翘抗炎活性的进一步研究提供基础。     

藏药菥蓂中黑芥子苷对黄嘌呤致小鼠高尿酸作用的研究北大核心CSCD

采用黄嘌呤致小鼠高尿酸模型,将昆明种小鼠随机分为模型组、空白对照组、阳性组、未灭活水提液(WMHSTY)组、灭活水提液(MHSTY)组、醇提液(CTY)组和水提醇沉浓缩液(STCCNSY)组并分别给药,以提取液对尿酸降低程度与提取液中黑芥子苷含量的关系阐明黑芥子苷与菥蓂治疗痛风作用的关系。结果,MHSTY和WMHSTY对黄嘌呤致小鼠高尿酸模型有显著的降低尿酸作用,两者间无明显差异,但黑芥子苷含量差异显著;CTY中黑芥子苷含量最高,但对本模型无明显作用;STCCNSY中无法检测出黑芥子苷,但对本模型有极显著作用。表明,藏药菥蓂中黑芥子苷的含量与菥蓂对黄嘌呤致小鼠高尿酸模型的作用无明显关系。     

Fever and cancer in perspective

CONTEXT: A relationship between feverish infection and concurrent remission from cancer has been known about for a very long time. However, a systematic investigation of the phenomenon has not yet been made. OBJECTIVE: To bring together the isolated observations about the coincidence of spontaneous remissions with feverish infections and William Coley's seminal work, as a basis for devising an immunological hypothesis about the putative anti-cancer effect of fever. CONCLUSION: Fever induction under medical guidance may be considered as part of a therapy regimen for cancers of mesodermal origin.     

A new mouse model reveals a critical role for host innate immunity in resistance to Rift Valley fever

Rift Valley fever (RVF) is an arthropod-borne viral disease repeatedly reported in many African countries and, more recently, in Saudi Arabia and Yemen. RVF virus (RVFV) primarily infects domesticated ruminants, resulting in miscarriage in pregnant females and death for newborns and young animals. It also has the ability to infect humans, causing a feverish syndrome, meningoencephalitis, or hemorrhagic fever. The various outcomes of RVFV infection in animals and humans argue for the existence of host genetic determinants controlling the disease. We investigated the susceptibility of inbred mouse strains to infection with the virulent RVFV ZH548 strain. Compared with classical BALB/cByJ mice, wild-derived Mus m. musculus MBT/Pas mice exhibited earlier and greater viremia and died sooner, a result in sharp contrast with their resistance to infection with West Nile virus and influenza A. Infection of mouse embryonic fibroblasts (MEFs) from MBT/Pas mice with RVFV also resulted in higher viral production. Microarray and quantitative RT-PCR experiments showed that BALB/cByJ MEFs displayed a significant activation of the type I IFN pathway. In contrast, MBT/Pas MEFs elicited a delayed and partial type I IFN response to RVFV infection. RNA interference-mediated inhibition of genes that were not induced by RVFV in MBT/Pas MEFs increased viral production in BALB/cByJ MEFs, thus demonstrating their functional importance in limiting viral replication. We conclude that the failure of MBT/Pas murine strain to induce, in due course, a complete innate immune response is instrumental in the selective susceptibility to RVF.     

汉滩病毒感染体外培养神经元损伤及抗体对其保护作用

用体外培养的昆明小鼠胚胎脑皮质神经元,感染汉滩病毒后,　检测原癌基因ＦＯＳ的表达,加入ＨＦＲＳ病人恢复期血清,观察其对神经元的保护作用。将病毒　感染的神经元经免疫组化染色,检测原癌基因ＦＯＳ的快速表达;在病毒感染的神经元内加入Ｈ　ＦＲＳ病人恢复期血清,使用ＭＴＴ比色试验检测神经元存活情况。病毒感染的神经元ＦＯＳ表达明　显　增高,与对照组相比有显著性差异（Ｐ＜０．００１）;　ＨＦＲＳ病人恢复期血清保护病毒感染的神经元　组　与感染对照组神经元活性明显不同,有显著性差异（Ｐ＜０．００１）。　ＨＴＮＶ感染体外培养的神经元　,会使细胞内产生ＦＯＳ的快速表达,ＨＦＲＳ病人恢复期血清对病毒感染的神经元有一定的保护　作用。     

内蒙地区发热患者血清中冠状病毒抗体的检测

目的分析内蒙地区发热患者中冠状病毒的感染情况。方法以SARS冠状病毒感染Vero细胞涂片为冠状病毒抗原片,用间接免疫荧光法分别检测55例发热患者和68例正常人血清中冠状病毒的IgG、IgM抗体。结果发热患者血清中冠状病毒IgG抗体和IgM抗体阳性率分别为29.1%(16/55)和10.9%(6/55),而正常人血清中只检测到2.9%(2/68)的IgG抗体,且未检测到IgM抗体,2组患者的IgG和IgM抗体阳性率比较差异均有显著性;随机选取7例患者的IgG阳性血清进行SRAS冠状病毒的特异性抗体封闭实验,结果有6例血清仍为阳性,有1例血清转为阴性,说明冠状病毒IgG抗体阳性血清中85.7%为普通冠状病毒特异性,14.3%为SARS冠状病毒特异性。结论普通冠状病毒是内蒙地区发热患者的主要病原体之一,部分患者还存在SARS冠状病毒的既往感染。     

丙型肝炎病毒感染实验动物模型的研究进展

丙型肝炎病毒（HCV）感染是导致人类慢性病毒性肝炎、肝硬化和肝癌的最主要病因之一。由于缺乏合适的HCV感染实验动物模型,使得针对HCV感染更为有效的疗法及疫苗的研发滞后。黑猩猩是HCV感染研究的最佳实验动物,但由于其来源有限、价格昂贵及临床症状等诸多问题,其应用受限,因此发展新的实验动物模型用于HCV感染相关的基础和应用研究迫在眉睫。近年来,以啮齿类等动物为替代模型取得了不少进展,应用转基因等实验技术使替代动物感染了HCV,并成功应用于多个学科领域的研究。本文分析了HCV自然感染的实验动物、自然感染和非自然感染的替代实验动物在致病机制研究、药物评价和疫苗研发应用中的优缺点及未来研究趋势。     

Effects of lipopolysaccharide and acclimation temperature on induced behavioral fever in juvenile Iguana iguana

We examined the effects of acclimation temperature and two doses (2.5 and 25mgkg(-1)) of a pyrogen (lipopolysaccharide, LPS) on behavioral thermoregulation in juvenile green iguanas. Overall means of body temperatures for the three-day trial periods were compared among three groups of animals acclimated at 15, 25, and 34 degrees C. The responses of each group of animals to the two dosages of LPS and a control saline injection were examined. Within each treatment block, animals either chose high body temperatures characteristic of a fever response or chose low body temperatures characteristic of a hypothermic response. Thermoregulation was influenced by interaction effects between and among, and independent effects of, acclimation temperature, dose of LPS, and day. In some treatment blocks, individual lizard mass positively correlated with mean individual body temperature. Mean mass of lizards that chose higher body temperatures within a treatment block was higher than the mean mass of lizards that chose lower body temperatures. From these results, we concluded that LPS may induce two different behavioral thermoregulatory responses: fever or hypothermia. The actual amplitude and direction of body temperature change appears to be affected by acclimation temperature and possibly by mass or energy reserves of the animal. If the energy reserves are not sufficient to sustain the higher rate of metabolism associated with the higher body temperatures of a hyperthermic or feverish state, the animal may resort to hypothermia.     

A genomic island of an extraintestinal pathogenic Escherichia coli Strain enables the metabolism of fructooligosaccharides, which improves intestinal colonization

Prebiotics such as fructooligosaccharides (FOS) are increasingly being used in some countries for improving human and animal health and as an alternative to antibiotic growth promoters in animals, with various degrees of success. It has been observed that FOS stimulate the proliferation of probiotic bacteria and, at the same time, decrease the population of bacteria associated with disease. This observation assumes that pathogenic bacteria do not metabolize FOS and, therefore, lose their competitive advantage over beneficial bacteria. Here we present evidence that some pathogenic Escherichia coli strains can metabolize FOS and show that this property helps the bacterium colonize the intestine. These findings highlight the potential risk that a high level of prebiotic usage could lead to the emergence of well-adapted pathogenic strains that metabolize prebiotic substances.     

A mouse model for the human pathogen Salmonella typhi

Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a life-threatening human disease. The lack of animal models due to S. Typhi's strict human host specificity has hindered its study and vaccine development. We find that immunodeficient Rag2(-/-) γc(-/-) mice engrafted with human fetal liver hematopoietic stem and progenitor cells are able to support?S. Typhi replication and persistent infection. A?S. Typhi mutant in a gene required for virulence in humans was unable to replicate in these mice. Another mutant unable to produce typhoid toxin exhibited increased replication, suggesting a role for this toxin in the establishment of persistent infection. Furthermore, infected animals mounted human innate and adaptive immune responses to S. Typhi, resulting in the production of cytokines and pathogen-specific antibodies. We expect that this mouse model will be a useful resource for understanding S.?Typhi pathogenesis and for evaluating potential vaccine candidates against typhoid fever.     

Physicochemical characterization of fructooligosaccharides and evaluation of their suitability as a potential sweetener for diabetics

Fructooligosaccharides (FOSs) were prepared from sucrose using fungal fructosyl transferase (FTase) obtained from Aspergillus oryzae MTCC 5154. The resulting mixture consisted of glucose (28-30%), sucrose (18-20%) and fructooligosaccharides (50-54%) as indicated by HPLC analysis. Identification of oligomers present in the mixture of fructooligosaccharides was carried out using NMR spectroscopy and LC-MS. No compounds other than mono-, di-, tri-, tetra- and pentasaccharides were identified in the FOS mixture prepared using FTase. NMR and LC-MS spectra proved the absence of any toxic microbial metabolites of Aspergillus species in FOS thereby emphasizing its safe use as a food ingredient. Animal studies conducted on streptozotocin-induced diabetic rats suggested that the use of FOS as an alternative non-nutrient sweetener is without any adverse effects on various diabetes-related metabolic parameters. Despite the high free-sugar content associated with it, FOS did not further aggravate the hyperglycemia and glucosuria in diabetic animals, even at 10% levels. On the other hand, by virtue of its soluble fibre effect, it has even alleviated diabetic-related metabolic complications to a certain degree.     

Stochastic effects on endemic infection levels of disseminating versus local contacts

The effects of two levels of mixing on endemic infection levels are shown to differ for identically conformed deterministic compartmental (DC) and stochastic compartmental (SC) models. Both DC and SC models give similar endemic levels when populations are large, immunity is short lived, and mixing is universal. But local transmissions and/or transient immunity decrease overall population infection levels in SC but not in DC models. DC models also fail to detect the greater effects of eliminating disseminating transmissions in comparison to eliminating local transmissions shown by SC models. These differences in model behavior arise because localities that encounter few infections from distant sites and that have stochastically low infection levels have decreased infection rates while localities with stochastically high levels of infection do not decrease the rate at which they lose infection. At the extreme this generates local stochastic die out with subsequent build up of susceptibility in SC but not DC models. This phenomenon should act upon all endemic infections that have changing geographic or social foci of infection. Neither standard epidemiological investigations nor sufficient-component cause models can capture these effects because they occur in the absence of differences between individuals.