0710合生元结肠靶向微生态调节剂体外释放及定位作用研究

目的将益生菌双歧杆菌与枸杞多糖提取物设计为口服结肠定位给药系统(OCDDS),制备0710合生元结肠靶向微生态调节剂,考查其体外释放行为及体内定位作用。方法以枸杞中多糖为指标,对制剂进行体外溶出实验,并利用X-射线跟踪技术验证0710合生元结肠靶向微生态调节剂在人体内的靶向性。结果该制剂在人工胃液2 h、人工小肠液4 h,几乎不释药,而在人工结肠液中6 h释药达到100%,符合中国药典2005年版对缓释制剂的规定,且体内实验在结肠中黏附性较好。结论0710合生元结肠靶向微生态调节剂在体外结肠液中释放良好,在体内结肠具有靶向性,达到制剂设计要求。     

叶酸介导的普鲁兰多糖- 阿霉素聚合物前药的制备及生物学性能初探

目的:制备叶酸介导的普兰多糖-阿霉素聚合物前药(FA-MP-DOX),实现阿霉素药物的靶向控制释放。方法:将普鲁兰多糖用马来酸酐进行修饰后,通过酰胺键键合阿霉素制备得到普鲁兰多糖-阿霉素(MP-DOX),继而酯键键合叶酸制备得到叶酸介导的普鲁兰多糖-阿霉素聚合物前药(FA-MP-DOX)。红外光谱、核磁共振光谱表征聚合物药物的结构,动态透析法模拟体外释药特性,监测不同pH值聚合物药物中阿霉素的释药特性,同时采用人口腔表皮样癌细胞(KB细胞)测定聚合物药物体系的细胞毒性。结果:①经核磁共振表征FA-MP-DOX聚合物合成完成。②在pH2.5、pH5.0及pH7.4的PBS缓冲体系16h中,阿霉素药物累积释放率分别为49.1%,30.3%和15.3%,证实FA-MP-DOX中阿霉素的释放具有pH依赖性。③细胞实验证实FA-MP-DOX的细胞毒性高于阿霉素和MP-DOX。结论:FA-MP-DOX聚合物药物有望成为阿霉素智能型控释和靶向性药物载体。     

叶酸介导的普鲁兰多糖-阿霉素聚合物前药的制备及生物学性能初探

目的：制备叶酸介导的普兰多糖-阿霉素聚合物前药（FA-MP-DOX）,实现阿霉素药物的靶向控制释放。方法：将普鲁兰多糖用马来酸酐进行修饰后,通过酰胺键键合阿霉素制备得到普鲁兰多糖-阿霉素（MP-DOX）,继而酯键键合叶酸制备得到叶酸介导的普鲁兰多糖-阿霉素聚合物前药（FA-MP-DOX）。红外光谱、核磁共振光谱表征聚合物药物的结构,动态透析法模拟体外释药特性,监测不同pH值聚合物药物中阿霉素的释药特性,同时采用人口腔表皮样癌细胞（KB细胞）测定聚合物药物体系的细胞毒性。结果：①经核磁共振表征FA-MP-DOX聚合物合成完成。②在pH2.5、pH5.0及pH7.4的PBS缓冲体系16h中,阿霉素药物累积释放率分别为49.1%,30.3%和15.3%,证实FA-MP-DOX中阿霉素的释放具有pH依赖性。③细胞实验证实FA-MP-DOX的细胞毒性高于阿霉素和MP-DOX。结论：FA-MP-DOX聚合物药物有望成为阿霉素智能型控释和靶向性药物载体。     

多糖颗粒复合PLGA微球用于脉冲式释药系统的研究

目的:考察多糖颗粒复合PLGA微球用作脉冲式释药系统的可行性.方法:用水相-水相乳化法将模型蛋白BSA包裹于多糖颗粒中,再用S/O/W法制备多糖颗粒复合PLGA微球.采用microBCA法测定该微球体外释放行为,并与W/O/W复乳法制备的BSA微球相对照.结果:用W/O/W复乳法制备的BSA微球的体外释放曲线显示,该微球在开始释放第一天起就出现一个平台期,之后则产生一个持续高释放量的行为.而多糖颗粒复合PLGA微球的体外释放曲线显示,其在释放第一天和一个较长平台期之后都出现峰形释放,相对于前者微球与脉冲释药模式更为相近.平台期时长与高分子性质有关,PLGA结构中乳酸相对于乙醇酸比例越高则平台期越长.结论:多糖颗粒复合PLGA微球具有良好的脉冲式释药效果,是一种较有前景的脉冲释药系统.     

甘草次酸结肠靶向微丸的研制

目的:确定甘草次酸结肠靶向微丸的制剂处方,评价其释药特性。方法:采用挤出-滚圆法制备甘草次酸素丸,利用流化床包衣技术对甘草次酸素丸进行包衣,用浆法评价微丸的体外释药性能。结果:采用微晶纤维素和甘草次酸,同时加入黏合剂羧甲基纤维素钠,经过充分搅拌混合,以30%的乙醇作为润湿剂,通过挤出-滚圆制得甘草次酸素丸。以尤特奇S100为膜控材料,加入适量柠檬酸三乙酯与滑石粉配制包衣液,对甘草次酸素丸进行包衣,制得甘草次酸包衣微丸。释放度实验表明甘草次酸素丸在其增重20%时,在0.1 mo L/L的盐酸溶液中不释放,在p H6.8的磷酸缓冲液条件下6 h内其释放率不到20%。而在p H7.4的磷酸缓冲液条件下2 h内释放率达到80%以上。结论:所制的甘草次酸素丸处方合理,制剂工艺简便,通过流化床包衣技术所制的甘草次酸包衣微丸在模拟的胃液中不释放,在小肠液中释放缓慢,在结肠液中释药良好,具有良好的结肠靶向作用。     

蛋白质药物口服的研究进展

蛋白质药物口服给药系统因其给药方便、顺应性好,逐渐成为一种最有前景的给药方式.从提高蛋白质药物生物利用度入手,综述采用结构修饰、吸收促进剂、酶抑制剂、结肠定位释药、脉冲式药物给药系统和受体介导靶向载体系统等方式,均可大大提高蛋白质药物的口服生物利用度和在胃肠道中的稳定性.     

β3肾上腺素受体介导多巴胺对大鼠远端结肠运动的抑制作用

目的研究多巴胺（DA）对大鼠结肠运动影响的机制。方法采用离体组织灌流方法记录大鼠远端结肠自发性节律运动,观察DA的作用以及阻断剂的影响,再用反转录实时多聚酶链反应（real time RT-PCR）检测受体基因的表达。结果DA（≥1.0×10-5mol/L）对结肠远端（紧接肛门淋巴结近端）离体纵行肌条（2.0 mm×10 mm）的运动具有抑制作用,多巴胺受体阻断剂（D1受体阻断剂SCH23390,1.0×10-7mol/L,D2受体阻断剂Sulpide,1.0×10-7mol/L）不能阻断多巴胺的抑制效应,但加入β3受体抑制剂cyanopindolol（7.5×10-7mol/L）,DA的抑制作用显著减弱。real time RT-PCR检测发现β1、β2、β3受体mRNA在远端结肠均有表达。结论DA可通过β3受体发挥对远端结肠运动的抑制作用。     

3种模拟中医体征的体虚便秘大鼠模型建立及效果观察

目的：分别建立大鼠血虚、阴虚和阳虚便秘模型并比较其结肠动力、结肠水代谢、结肠黏液分泌和结肠水通道蛋白2（AQP2）的表达水平。方法：40只SD大鼠,雌雄各半,随机分为4组（n=10）：正常对照组（N）、血虚便秘组（XC）、阴虚便秘组（YC）、阳虚便秘组（YAC）。分别采用放血+洛哌丁胺、甲状腺素+洛哌丁胺、冰水刺激+洛哌丁胺建立血虚便秘、阴虚便秘、阳虚便秘大鼠模型,放血每周1次,药物每天灌胃1次,连续42 d。检测大鼠活动状态、体质量、大便性状、口肛传输时间、小肠推进率、粪便和结肠含水量等体征指标,对结肠组织进行AB-PAS染色和免疫组化染色,观察黏液分泌情况和AQP2表达水平。结果：与正常对照组比较,3种模型大鼠体重增长减慢;造模第40天自主活动量变化率由大到小依次为YC、XC和YAC;造模第30天出现固体硬质粪便,粪便评分升高顺序为XC、YC和YAC;口肛传输时间均显著延长、小肠推进率均显著降低（P < 0.05,P < 0.01）,肠动力减低顺序为YC、YAC和XC;粪便含水量均显著减少（P < 0.05,P < 0.01）,XC和YAC组大鼠结肠含水量显著减少（P < 0.05,P <0.01）,YC大鼠结肠含水量有减少趋势,结肠水代谢顺序为YC、YAC和XC;3种模型大鼠结肠黏膜层腺管和杯状细胞出现不同程度缩小,黏液分泌减少,分泌功能障碍顺序为YAC、YC和XC,且近端和远端结肠AQP2的表达均显著增加（P < 0.05,P < 0.01）,增加顺序近端结肠为YAC、YC、XC,远端结肠为YAC、XC和YC。结论：复合因素长期刺激均可建立符合中医体征的便秘大鼠模型,且各模型大鼠结肠运动、结肠水代谢、结肠黏液分泌和AQP2表达水平存在一定的差异。     

大鼠肠道自发荧光微生物的分布

目的探讨不同发育阶段大鼠肠道自发荧光微生物在肠道内的分布。方法采用Kinetics IVIS小动物活体成像系统的荧光检测技术对不同发育阶段SD大鼠肠道内自发荧光微生物在肠道内的分布位置进行检测和评估。先对体外培养的大肠杆菌标准菌株进行荧光检测,然后在同一检测条件下分别对大肠杆菌的分布位置进行检测。扩大荧光检测激发光波长范围,去除饲料和粪便等外来自发荧光物质的荧光背景,分别检测出生3、14 d和60 d的SD大鼠肠道内自发荧光微生物的分布。结果大肠杆菌在485~535 nm激发波长范围内能发荧光。大肠杆菌在出生3 d的SD大鼠肠道系统中主要分布于胃,少量分布于回肠;在出生14 d的SD大鼠肠道系统中主要分布于胃和盲肠,少量分布于回肠;在出生60 d的SD大鼠肠道系统中主要分布于回肠内,少量分布于空肠、结肠和盲肠内。扩大荧光检测激发光波长范围后,自发荧光微生物在出生3 d的SD大鼠肠道系统中主要分布于回肠,其次是胃;在出生14 d的SD大鼠肠道系统中主要分布于胃,其次是盲肠,少量分布于回肠和空肠;在出生60 d的SD大鼠肠道系统中均有分布,主要分布于回肠和盲肠。结论采用小动物活体成像系统荧光检测技术检测自发荧光肠道微生物,对研究肠道微生物在寄主不同发育阶段肠道内的分布有一定的帮助和指导作用,为肠道微生物与寄主和经胃肠道给药关系的研究提供一定的依据。     

棕色田鼠胃肠道5-羟色胺细胞的免疫组织化学定位

应用ABC免疫组织化学方法,对棕色田鼠胃肠道内5-羟色胺细胞进行了免疫组织化学定位和形态学观察.结果 表明:5-HTIR细胞在棕色田鼠胃肠道的各段均有分布,其中以十二指肠和直肠段分布密度最高,胃底、胃幽门部、空肠、回肠、盲肠段其次,胃贲门部、胃体、结肠段分布密度最低.5-羟色胺细胞位于胃腺上皮、肠粘膜上皮、肠腺上皮及固有膜,有圆形、椭圆形、梭形、楔形和不规则形,有的还具有胞突.对棕色田鼠胃肠道5-HTIR细胞的分布、形态与功能相适应的特点进行了讨论.     

六种藓类植物茎的比较解剖学研究

通过对6种藓类植物,即褶叶青藓(Brachythecium salebrosum(Web.et Mohr.)B.S.G.)、湿地匐灯藓(Plagiomnium acutum(Lindb.)Kop.)、侧枝匐灯藓(Plagiomnium maximoviczii(Lindb.)Kop.)、大凤尾藓(Fissidensnobilis Griff.)、大羽藓(Thuidium cymbifolium(Doz.et Molk.)B.S.G.)和大灰藓(Hypnum plumaeforme Wils.)嫩茎和老茎的石蜡切片和显微观察发现,同一藓类植株的嫩茎和老茎,茎结构稳定,不同种藓类植物茎横切面具有不同特征.植物体茎横切面形状、表层细胞的层数、细胞大小和细胞壁厚薄、皮层细胞大小和形状、中轴的有无以及比例等特征可以作为藓类植物的分科分类依据之一.     

Photoregulation of seed germination of wild-type and of an aurea-mutant of tomato

Seed germination of an aurea mutant of tomato ( Lycopersicon esculentum Mill.) is promoted by continuous irradiation with red, far-red or long-wavelength far-red (758 nm) light as well as by cyclic irradiations (5 min red or 5 min far-red/25 min darkness). Far-red light applied immediately after each red does not change the germination behaviour. Seed germination of the isogenic wild-type, cv. UC-105, is promoted by continuous and cyclic red light while it is inhibited by continuous and cyclic far-red light and by continious 758 nm irradiation. Far-red irradiation reverses almost completely the promoting effect of red light. The promoting effect (in the aurea mutant) and the inhibitory effect (in the wild-type) of continuous far-red light do not show photon fluence rate dependency above 20 nmol m⁻² s⁻¹. It is concluded that phytochrome controls tomato seed germination throgh low energy responses in both the wild type and the au mutant. The promoting effect of continuous and cyclic far-red light in the au mutant can be attributed to a greater sensitivity to P_fr.     

Cause of Senescence of Nine Sorts of Flowers

The levels of endogenous phytohormones and respiratory rate in nine sorts of flowers such as Cymbidium faberi Rolfe, Nopalxochia ackermannii Kunth and others were investigated both at full bloom and senescence and meanwhile the effect of exogenous phytohormones on prolonging the blossoms and promoting ethylene production were tested. There is a high content of endogenous ethylene in all the long-lived flowere, about 3–16 folds higer than the short-lived ones. There is a high level of ABA at full blooming flowers of short-lived flowers, in which there is no or only some cytokinins in it, but the ratio of CTK (6BA+zeatin)/ABA is smaller(l.7). The endogenous ABA reached a much higher level at senescence in all nine sorts of flowers, so it is reasonable to consider that it is ABA which plays an important role of regulation in controlling flower's senescence. There is a much higher level of GA3 and zeatin in the long-lived flowers which is not demonstrated in the shortlived ones. The respiratory rate is one of the factors controtling the longevity of flowers, but it does not play a decided role. Application of 6BA and zeatin prolongs distinctly orchid’s longevity, however exogenous IAA through the promotive action on ethylene production, evidently extends the longevity of the flowers of the Nopalxochia ackermannii Kunth.     

龙胆科药用植物化学成分的研究现状

龙胆科植物在我国的分布范围很广,且多数为药用植物,其多数种属的药用植物,至今其化学成分尚未被系统研究。综述了目前龙胆科药用植物的化学成分的研究现状及一般提取方法,对近年来发现的环烯醚萜及裂环烯醚萜类化合物进行了总结,为本科药用植物的更深入研究提供了参考。     

Interconnection of parameters of regulation system of lipid peroxidation and of morphophysiological parameters of mouse liver

A complex analysis of seasonal fluctuations of the mean group parameters of the system of regulation of lipid peroxidation has been performed in liver of Balb/c mice. Association of lipid characteristics and morphophysiological parameters is studied in the Balb/c mouse liver. An inter-connection is revealed between the liver index and the amount of lysoforms of phospholipids, the scale and character of the interconnection differing essentially depending on proportion of phos-phatidylcholine in mouse liver phospholipids.     

真菌类遗传学分析的知识结构教学

本文以认知结构理论为指导,讨论了真菌类遗传分析与高等动植物遗传分析的内在联系,认为利用这种内在联系进行教学可收到好的效果并说明了作者的具体教学过程。 Abstract:In the paper, the relationship between genetic analysis of Fungi and genetic analysis of high animal and plant was discussed.A good results were obtained when we adopted this method in the teaching.     

Physiological characteristics of various species of strains of carboxydobacteria

Seven strains of aerobic carbon monoxide-oxidizing bacteria (carboxydebacteria) when growing on CO as sole source of carbon and energy had doubling times which ranged from 12–42 h. The activity profiles obtained after discontinuous sucrose density gradient centrifugation indicated that the CO-oxidizing enzymes are soluble and the hydrogenases are membrane-bound in all strains examined. The CO-oxidizing enzymes of Pseudomonas carboxydohydrogena, Pseudomonas carboxydoflava, Comamonas compransoris, and the so far unidentified strains OM2, OM3, and OM4 had a molecular weight of 230,000; that of Achromobacter carboxydus amounted to 170,000. The molecular weights of the CO-oxidizing and H₂-oxidizing enzymes turned out to be identical. The cell sonicates were shown to catalyze the oxidation of both CO and H₂ with methylene blue, thionine, phenazine methosulfate, toluylene blue, dichlorophenolindophenol, cytochrome c or ferricyanide as electron acceptors. Methyl viologen, benzyl viologen, FAD⁺, FMN⁺, and NAD(P)⁺ were not reduced. The spectrum of electron acceptors was identical for all strains tested. Neither free formate, hydrogen nor oxygen gas were involved in the CO-oxidation reaction. Methylene blue was reduced by CO at a 1:1 molar ratio. The results indicate that CO-oxidation by carboxydobacteria is catalyzed by identical or similar enzymes and that the reaction obeys the equation CO+H₂OCO₂+2H⁺+2e^- as previously shown for Pseudomonas carboxydovorans.Dedicated to Otto Kandler remembering almost three decades of enjoyable cooperation     

The effects of glutamine of the maintenance of embryogenic cultures of Cryptomeria japonica

Summary Embryogenic tissues of sugi (Cryptomeria japonica) were induced on a modified Campbell and Durzan (CD) medium containing 1 μM 2,4-dichlorophenoxyacetic acid (2,4-D) and 600 mg l⁻¹ glutamine, and subcultured in the medium of the same composition for over 1 yr. This resulted in a mixed culture of embryogenic and non-embryogenic cells. When embryogenic cells were isolated and cultured independently, their capacity to form embryogenic aggregates was lost. Thus, the non-embryogenic cells present within a mixed culture system were essential to the formation of embryogenic aggregates. When embryogenic tissues were isolated and cultured independently on a high glutamine-containing (2400 mg l⁻¹) medium, dry weights and endogenous levels of glutamine increased, and the tissue could generate a large number of embryogenic aggregates. Amino acid analysis of embryogenic and non-embryogenic cells from the maintenance culture indicated a higher level of glutamine was present in the latter. The high endogenous level of glutamine in the non-embryogenic portion of mixed cell masses may be the supplier of glutamine for maintaining the embryogenic property of the tissues.