清毒颗粒抑制免疫逃逸防治大鼠乳腺癌的药效学研究

摘 要 目的： 探讨清毒颗粒对二甲基苯蒽(DMBA)诱导SD大鼠乳腺癌的药效。方法: DMBA诱导大鼠乳腺癌,观察清毒颗粒对肿瘤抑制率,HE染色观察病理特点,IHC检测肿瘤组织Ki 67分布及含量,ELISA检测大鼠血清中IL-12、IFN-γ、IL-4和IL-10含量。结果: 低、中、高剂量清毒颗粒和柴胡皂苷a的抑瘤率分别为：30.93%,43.84%,44.17%和43.48%;清毒颗粒和柴胡皂苷a可显著降低Ki 67表达量;上调血清中IL-12、IFN-γ含量,下调IL-4、IL-10含量。结论: 清毒颗粒具有抗乳腺癌作用,其机制可能是调节机体免疫,增强抗肿瘤免疫作用。     

Live porcine reproductive and respiratory syndrome virus vaccines: Current status and future direction

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) was reported in the late 1980s. PRRS still is a huge economic concern to the global pig industry with a current annual loss estimated at one billion US dollars in North America alone. It has been 20 years since the first modified live-attenuated PRRSV vaccine (PRRSV-MLV) became commercially available. PRRSV-MLVs provide homologous protection and help in reducing shedding of heterologous viruses, but they do not completely protect pigs against heterologous field strains. There have been many advances in understanding the biology and ecology of PRRSV; however, the complexities of virus-host interaction and PRRSV vaccinology are not yet completely understood leaving a significant gap for improving breadth of immunity against diverse PRRS isolates. This review provides insights on immunization efforts using infectious PRRSV-based vaccines since the 1990s, beginning with live PRRSV immunization, development and commercialization of PRRSV-MLV, and strategies to overcome the deficiencies of PRRSV-MLV through use of replicating viral vectors expressing multiple PRRSV membrane proteins. Finally, powerful reverse genetics systems (infectious cDNA clones) generated from more than 20 PRRSV isolates of both genotypes 1 and 2 viruses have provided a great resource for exploring many innovative strategies to improve the safety and cross-protective efficacy of live PRRSV vaccines. Examples include vaccines with diminished ability to down-regulate the immune system, positive and negative marker vaccines, multivalent vaccines incorporating antigens from other porcine pathogens, vaccines that carry their own cytokine adjuvants, and chimeric vaccine viruses with the potential for broad cross-protection against heterologous strains. To combat this devastating pig disease in the future, evaluation and commercialization of such improved live PRRSV vaccines is a shared goal among PRRSV researchers, pork producers and biologics companies.     

地塞米松脂质体的制备及其对乳腺癌作用的体内外研究

目的制备地塞米松脂质体,探讨地塞米松对乳腺癌4T1细胞的生长抑制作用及对荷瘤鼠的抗肿瘤药效。方法采用薄膜分散–超声法,以粒径和多分散指数(PDI)为指标进行单因素实验考察了大豆磷脂(SPC)与甲氧基聚乙二醇磷脂(DSPE-mPEG2000)的质量比、SPC与地塞米松的质量比、超声时间对地塞米松脂质体粒径的影响从而筛选得到最佳处方和最佳工艺条件。采用MTT法比较地塞米松注射液和地塞米松脂质体对4T1细胞的作用。建立4T1 BAL B/c荷瘤小鼠模型,研究地塞米松脂质体对4T1荷瘤小鼠的体内抗肿瘤作用。结果当SPC与DSPE-mPEG2000质量比为5∶1、SPC与地塞米松质量比为50∶3、超声时间为20 min时制备得到的脂质体粒径最小,粒径分布最窄,室温放置15 d稳定,于生理介质中稳定。MTT测定结果显示地塞米松注射液和脂质体对4T1细胞生长抑制作用均较弱,但在4T1荷瘤鼠的体内实验中,在5mg/kg的给药剂量下,地塞米松脂质体的抑瘤率却高达78.9%,显著高于地塞米松注射液(33.4%,P<0.05)和8mg/kg紫杉醇注射液(55%,P<0.05)。结论制备的地塞米松脂质体放置于生理介质中均能稳定存在,能口服能静脉给药。地塞米松脂质体对4T1荷瘤小鼠肿瘤生长有较强的抑制作用,但体外对4T1细胞抑制抑制作用并不强,推测地塞米松脂质体是通过调节肿瘤微环境来抑制肿瘤生长。     

安神补脑液对大鼠长期毒性的观察

目的 观察安神补脑液长期灌胃给药对大鼠所产生的毒性反应及严重程度, 提供毒副反应的靶器官及其损害的可逆程度, 确定无毒反应剂量, 以评价安神补脑液长期用药的安全性, 为拟定临床试验剂量及观察指标提供参考。方法 Wistar大鼠随机分为安神补脑液低、中、高剂量组(2.5、5、10 mL/kg)和溶剂对照组(灌服同容积蒸馏水 2 mL/100 g), 每组60只, 雌雄各半, 每天给药1 次, 每周给药6 d, 连续26周。观察大鼠的外观行为、体重、摄食量, 并分别于给药第13、26周末及四周恢复期结束进行血液学及血液生化学等各项指标检测及脏器系数、病理组织学检查。结果 长期连续灌胃给予安神补脑液, 对动物一般状态、行为活动和外观体征无明显不良影响;各剂量组的摄食量、体重、血液学及血液生化学指标与对照组比较无明显差别;给药3个月、6个月对动物各脏器组织位置、重量和脏器系数无不良影响, 但部分脏器重量有所增加, 各组动物脏器系数在正常范围内;病理结果显示对照组和安神补脑液高剂量组动物未见明显与给药相关的异常病理改变和毒性改变, 恢复期停药后未见延迟性毒性, 因此, 中、低剂量组动物各脏器组织无需进行组织病理形态学检查。结论 安神补脑液长期用药对大鼠未见明确的毒性反应, 停药后亦无延迟性毒性反应, 预期拟定的临床用药量为安全剂量。     

三七素的药理作用研究进展

三七素是一种天然存在的非蛋白氨基酸,主要存在于三七中。三七素具有多种药理作用,文献报道最多的是止血作用。此外,三七素还具有神经保护作用、减轻糖尿病肾病损伤作用、抗炎作用及降血糖等作用。近年来对三七素的相关研究逐渐增多,主要综述三七素的药理作用研究进展,期望为今后三七素的进一步研究和开发利用提供参考。     

毛重楼叶绿体基因组序列特征及其系统发育分析

目的获取毛重楼Parismairei叶绿体基因组信息特征并对其系统位置进行研究。方法采用Illumination测序技术对毛重楼叶绿体基因组进行测序,对其进行组装、注释和特征分析,并构建最大似然(maximumlikelihood,ML)系统发育树。结果毛重楼叶绿体基因组大小为163 918 bp,总GC含量为37.05%,大单拷贝区(large single-copy,LSC)、小单拷贝区(smallsingle-copyregion,SSC)分别为84173、13054bp,反向互补重复区(invertedrepeats,IR)大小为33296bp,共编码113个基因,包括79个蛋白质编码基因,30个t RNA基因和4个r RNA基因。在系统进化树中,重楼属Paris L.与藜芦科(Melanthiaceae Batsch ex Borkh.)关系较近,与百合科(Liliaceae Juss.)关系较远。结论 LSC区和SSC区序列变异高于IR区;相较于重楼属,毛重楼与蚤休组的亲缘关系最近,应将毛重楼归属为蚤休组;相较于百合科,毛重楼与藜芦科藜芦属亲缘关系更近,应将蚤休组从百合科中独立,归属为藜芦科。     

绿原酸酰胺二聚体的合成及体外抗脂质代谢紊乱活性研究

目的设计合成绿原酸的酰胺二聚体衍生物,并对其进行体外抗脂质代谢紊乱活性的研究.方法以绿原酸为起始原料经3步反应制得目标化合物,利用HepG2细胞株评价该类化合物的调血脂活性.结果 设计并合成8个绿原酸酰胺二聚体衍生物CGA-2a~2d及CGA-3a~3d,均经波谱技术确证结构.药理实验结果表明,衍生物CGA-2d和CGA-3a~3d具有不同程度的调血脂活性.结论 绿原酸二聚体化合物CGA-2a~2d及CGA-3a~3d均为未见文献报道的新化合物,部分化合物具有潜在的调脂生物活性,具有深入研究价值.     

The effects of surface morphology on the aerosol performance of spray-dried particles within HFA 134a based metered dose formulations

The aim of this study was to produce fine particles with different corrugated degree of surface by spray-drying and to investigate the effect of surface morphology on in vitro aerosol performance of the particles within HFA 134a based metered dose formulations. Compositions of rizatriptan and scutellarin were spray-dried using different spray-drying parameters, and particles were suspended within HFA 134a. The surface morphology were determined using scanning electron microscopy (SEM), while the aerodynamic performance of MDIs was evaluated using a next generation pharmaceutical impactor. The surface morphology of spray-dried particles could vary from smooth to moderately corrugated, and to raisin-like depending upon spray-drying parameters and preparation compositions. In general, increasing inlet temperature, decreasing feed concentration and/or adding leucine to the feed solution tended to increase the corrugated degree of particle surface. Deposition results indicated that raisin-like particle based MDIs for all compositions of the two drugs produced significantly better aerodynamic performance in terms of fine particle fractions and mass median aerodynamic diameters relative to the formulations of the corresponding smooth or slightly corrugated particles when the particle compositions were the same. The present results demonstrated that wrinkled particles increased fine particle fractions within surfactant-free MDI formulations.     

毛叶巴豆中的倍半萜类成分

从毛叶巴豆茎中分离得到2个倍半萜类化合物，其中化合物1为一个新化合物，应用HREI-MS，^1H-NMR，^13C-NMR，^1H-H COSY,HMQC，HMBC和NOESY等光谱测定了其结构，并命名为毛叶巴豆醇。然而，文献检索发现该结构被错误地鉴定为Homalomenol D，通过仔细分析文献报道的核磁数据并与化合物1比较，发现文献中Homalomenol D结构鉴定有误，应该修正为5-表毛叶巴豆醇。化合物2鉴定为日本刺参萜酮。