一种有效的小鼠气道内siRNA给药方式模型建立

目的建立一种有效的哮喘小鼠气道内siRNA给药方式。方法雌性BALB／c小鼠以卵蛋白致敏法建立哮喘小鼠模型后,以NF-κB（p50）基因为靶基因,通过自制雾化器分别将NF-κB siRNA（20μmol／L,100μL／只）溶液及相同浓度的非干扰siRNA溶液分别雾化注射入实验组和对照组小鼠气道内。给药后,处死小鼠取肺组织,通过荧光定量PCR检测NF-κB基因表达变化,确定该给药方式的有效性。结果通过直接气道内雾化给药的方式能显著降低NF—KB基因表达水平（NF-κB下调1．743倍,P=0．0035）。结论采用气道直接雾化给药的方法能有效降低靶基因的表达。     

抗菌肽JH-3治疗沙门氏菌感染的效果评价

【目的】沙门氏菌(Salmonella)是重要的人畜共患传染病原菌,其感染是引起世界性胃肠疾病的主要因素,全球每年大概有2 100万伤寒病例,给世界公共卫生带来严重威胁。目前抗生素滥用问题严峻,急需寻找一种抗生素的替代品。抗菌肽JH-3是本实验室分离并人工改造后具有广谱杀菌活性的小肽,以沙门氏菌标准菌株CVCC541为研究对象,在小鼠模型上评价抗菌肽JH-3治疗沙门氏菌感染的效果。【方法】在CVCC541感染BALB/c小鼠前3 d连续腹腔注射抗菌肽JH-3或环丙沙星(B3d,共计40 mg/kg)和感染后3 d连续注射JH-3或环丙沙星(P3d,共计40 mg/kg)进行治疗。【结果】发现环丙沙星预防组效果最佳,抗菌肽JH-3的预防组(B3d)效果较好,可显著保护小鼠免受致死剂量CVCC541的攻击,小鼠存活率高达100%,临床症状评分、血液和脏器荷菌数降低,小肠段病理变化减轻,效果与环丙沙星治疗组相当;而感染3 d后JH-3治疗效果较差,临床症状评分、脏器荷菌量以及小肠病理变化均显著高于3 d前预防组,但3 d后治疗组小鼠存活率为70%,仍明显高于单独感染组。【结论】系统评价了抗菌肽JH-3不同给药时间对沙门氏菌感染的治疗效果,预防性给药方式的抗菌作用最佳,与环丙沙星治疗效果相当,为新型抗菌药物的研究提供参考。     

山苍子油对小鼠系统性白念珠菌感染的影响

目的研究山苍子油对小鼠系统性白念珠菌感染的治疗作用。方法建立小鼠系统性白念珠菌感染模型,观察给药后小鼠中位生存时间,并检测给药后小鼠肾脏菌落形成单位计数。结果山苍子油能明显延长小鼠的中位生存时间,降低肾脏菌落形成单位计数。结论山苍子油对小鼠系统性白念珠菌感染具有治疗作用,值得进一步研究和开发。     

雄黄纳米微粒在细胞水平上抑制呼吸道合胞病毒复制的初步研究

建立呼吸道合胞病毒A型(RSV-A型)感染Hep-2细胞模型,通过预防、治疗及直接灭活三种不同给药方式,观察中药雄黄对RSV-A型感染Hep-2细胞病变(CPE)的抑制作用。用高能球磨机研磨双蒸水水飞处理制备雄黄纳米微粒,应用砷钼蓝染色法测定雄黄纳米微粒浓度并在Nano Series粒度测定仪上测定其粒度。以MTT法计算药物的半数中毒剂量(TC50)。通过三种不同给药方式即预防给药、治疗给药及直接灭活给药方式进行体外实验,以利巴韦林为阳性对照药,观察雄黄纳米微粒对RSV-A型感染Hep-2细胞病变所起的作用,并对药物的量效关系进行分析。雄黄纳米微粒TC50值为0.649μg/mL。预防、治疗及直接灭活给药方式均可减轻RSV-A感染Hep-2细胞的CPE程度,其抑制RSV-A型感染Hep-2细胞病变的半数有效浓度(IC50)分别为0.20μg/mL、0.13μg/mL、0.16μg/mL,治疗指数(TI)分别为3.18、4.99和4.11,雄黄纳米微粒对RSV-A型感染Hep-2细胞病变的抑制作用存在着明显的量效关系。雄黄纳米微粒按预防、治疗及直接灭活给药方式给药时,其中治疗给药方式更有利于减轻RSV-A感染Hep-2细胞引起的病变。     

抗蜱传脑炎病毒的中和单克隆抗体在体内的特性

正蜱传脑炎病毒(TBEV)是黄病毒科中最重要的蜱传播病原体,也是人类最严重的神经感染病因。在本研究中,作者检测了一种具有中和作用的鼠源单抗14D5对感染TBEV的BALB/c小鼠的预防和治疗效果,该单抗之前被证明与几种属于TBEV群的虫媒病毒有交叉结合。感染前后,给小鼠注射14D5,剂量分别为每只小鼠100 μg和10 μg。感染后1天高剂量注射14D5显示出明显的保护效果,存活率呈TBEV剂量依赖性。预防性给予14D5比感染后给药更有效,     

不同特性粘数壳聚糖降血浆胆固醇、甘油三酯及抗氧化活性研究

通过醋酸-H2O2氧化降解法制备三种不同特性粘数（50℃时,η=4．76mL／g,29．39mL／g和54．93mL／g）的壳聚糖。以小鼠为实验对象,采取灌胃给药方式,考察其降低血浆TCH、TG的能力,并以血浆SOD酶活及MDA含量为指标,进行抗氧化药效学评价。结果显示,给药21d后,三种壳聚糖均能显著降低小鼠血浆TCH和TG含量,降幅分别大于28．2％和22．5％;且三种壳聚糖也能显著降低小鼠血浆MDA含量,降幅大于30．0％,但对小鼠血浆SOD酶活则无显著影响。     

流感泰得在小鼠体内抗H1N1型FM1株流感病毒活性研究

目的:研究流感泰得预防给药在小鼠体内对H1N1型FM1株流感病毒的抑制作用及对病毒感染小鼠的保护作用。方法:BALB/c小鼠随机分为正常对照组,病毒对照组,磷酸奥司他韦组,流感泰得2.5、5、10 mg/kg组,提前24h和1 h滴鼻给药2次,于第二次给药1 h后滴鼻感染小鼠造成肺炎模型,连续观察14 d,统计小鼠存活率、平均存活天数、体重变化;按以上方法于造模后第5 d天取肺脏,计算肺指数、肺脏病毒滴度。结果:与病毒对照组相比,流感泰得3个剂量组可明显提高病毒感染小鼠的存活率,延长平均存活时间,缓解病毒感染引起的体重降低,降低病毒感染小鼠的肺指数和肺脏病毒滴度。结论:流感泰得在小鼠体内预防给药具有抗H1N1型FM1株流感病毒活性。     

血必净注射液干预甲型H1 N1流感重症肺炎小鼠的疗效及机制研究

目的：观察血必净注射液（血必净）治疗甲型H1 N1流感重症肺炎小鼠的疗效,并初步研究其作用机制。方法：C57BL／6小鼠随机分为正常组、模型组、血必净组,正常组小鼠予20μL PBS滴鼻,模型组小鼠2×105 TCID50／20μL甲型H1 N1流感病毒液滴鼻感染,建立流感重症肺炎小鼠模型。血必净组小鼠2×105 TCID50／20μL甲型H1 N1流感病毒液滴鼻感染,并于感染前24 h腹腔注射给药,1次／d,连续给药5 d。通过观察、检测不同时间点各组小鼠的存活率、体重、肺病毒载量、肺湿干比、肺组织病理、肺灌洗液细胞因子等结果,评价血必净干预小鼠流感重症肺炎的疗效,初步探讨其作用机制。结果：模型组小鼠存活率为30％,体重下降明显,肺湿干比明显高于正常组（P＜0．05）,提示严重肺水肿;肺组织病理显示,双肺弥漫性炎性反应细胞浸润,肺泡上皮细胞脱落、坏死,支气管上皮细胞变性,伴有水肿、瘀血、出血,提示流感重症肺炎模型成立。血必净组小鼠存活率为60％,较模型组为优,但无统计学意义（P＞0．05）,体重下降较模型组轻,肺湿干比较模型组降低,但无统计学意义（P＞0．05）;肺组织病理示炎症细胞浸润,肺脏水肿,淤血、出血等严重程度均较模型组轻,提示血必净可减轻甲型流感重症肺炎小鼠的肺损伤。模型组与血必净组肺病毒载量无统计学意义（P＞0．05）,提示血必净并无抑制病毒复制的作用。血必净组可于感染后1 d、3 d降低TNF-α水平（P＜0．05）,于感染后3 d降低IL-6水平（P＜0．05）。结论：血必净对流感重症肺炎小鼠有减轻肺损伤及死亡保护趋势,但作用不显著,这可能与血必净并无直接抗病毒,但能调节感染早期TNF-α、IL-6等细胞因子水平的作用有关。     

PLGA-奥沙利铂缓释微球急性毒性实验

目的了解PLGA-奥沙利铂缓释微球和奥沙利铂小鼠皮下给药的急性毒性。方法采用Bliss法分别测定PLGA-奥沙利铂缓释微球和奥沙利铂小鼠皮下给药对动物的半数致死量（LD50）。结果PLGA-奥沙利铂缓释微球小鼠皮下给药时的LD50为660.90 mg/kg,奥沙利铂小鼠皮下给药时的LD50为15.24 mg/kg,相差达43.37倍。结论PLGA-奥沙利铂缓释微球能够显著降低药物对动物的急性毒性。     

抗炭疽人源化单抗在炭疽芽孢致死小鼠模型中的治疗效力评价

目的:建立炭疽芽孢(疫苗株A16R)攻击DBA/2J小鼠的致死模型,并使用该模型评价抗炭疽人源化单抗5E11的治疗效力。方法:用不同剂量A16R芽孢背部皮下攻击小鼠,计算半数致死剂量(LD_(50));ELISA定量检测5E11在小鼠体内的药代动力学参数;用100倍LD_(50)的芽孢攻击小鼠,攻毒后不同时间用不同剂量的5E11单抗治疗小鼠,观察小鼠存活等情况。结果:A16R芽孢攻击DBA/2J小鼠的LD50为7.8×10～3CFU;5E11在小鼠体内的平均消除半衰期约为7 d;攻毒后1 d给药的几个剂量组能够完全保护,攻毒后2～3 d给药能够提供40%～80%的保护。结论:抗炭疽人源化单抗5E11在芽孢攻击致死小鼠模型中表现出良好的保护效果,具有紧急治疗炭疽芽孢感染导致的急性炭疽的潜力。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.