多糖多相脂质体的物理性质与稳定性研究

本文主要研究多糖多相脂质体的物理性质——多相脂质体加热灭菌前后的形状、结构、粒度分布变化以及对药物丝裂霉素的包封率和聚结稳定性。实验证明:多糖多相脂质体的热稳定性好。经100℃60 min灭菌可保持完整多相脂质体形态、均匀的粒径与稳定的包封率。用Coulter计数仪测定了贮存过程中聚结成人粒子的变化规律。测得其聚结活化能E=99.992 kJmol^-1,是比较稳定的多相脂质体。     

人参多糖多相脂质体对免疫功能的影响及抗癌作用

人参多糖多相脂质体对免疫功能的影响及抗癌作用江春顾学裘高颖王俊平以巨噬细胞ＥＡ花环形成率为指标，证明了人参多糖多相脂质体（ＺＭ１，ＺＭ２）可激活正常或荷瘤小鼠腹腔巨噬细胞ＦＣ受体，将有助于改善机体的免疫功能，增强巨噬细胞对肿瘤的攻击能力．同时还证明，...     

酵母多糖脂质体的免疫增强作用

本文比较了酵母多糖脂质体、酵母多糖及脂质体对小鼠免疫功能的影响。结果表明,前两者对小鼠免疫功能均有促进作用,但经脂质体包封后的酵母多糖(多糖脂质体)表现出更强的促进能力,其差异有显著性(P＜0.01)。单纯脂质体的免疫增强作用不明显。     

抗癌药物新剂型——多相脂质体的研究 (Ⅶ) 喜树碱多相脂质体的研究(简报)

<正> 前报研究了油酸多相脂质体、复方唐松草新碱多相脂质体和复方氟尿嘧啶多相脂质体,本研究是继续开拓多相脂质体在抗癌药方面的应用范围,选用的药物是喜树碱。美国癌症研究所Wall等发现喜树Camptotheca acuminata树干的醇浸出液对小鼠腺癌有抑制作用,并分离出有效成分生物碱——喜树碱Camptothecin。Gallo等报告,喜     

喜树碱多相脂质体对肿瘤细胞动力学及分子药理学研究

喜树碱多相脂质体对肝癌细胞具有抑制增殖的效应,明显损伤S期细胞,对于G_0期细胞亦有轻度损伤,G_2期细胞进入M期也受到一定抑制。10mg/kg静注后肝癌组织中cAMP水平明显增加,而肝癌组织中DNA和蛋白质含量显著下降,cAMP与cGMP比值大幅度提高。喜树碱多相脂质体对肝癌细胞DNA合成的最高抑制率为73.7%,后作用约4小时,对癌细胞RNA合成的抑制率达82.9%。     

氨甲喋呤多相脂质体的制备及其动物抑瘤活性和临床前药理学实验研究

采用融熔法制备了氨甲喋吟(MTX)多相脂质体,并进行了抑瘤活性、小鼠急性毒性、家兔亚急性毒性和安全性实验。结果表明多相脂质体剂型显著提高了 MTX 对小鼠 EC 和 L615瘤株的抑瘤活性。急性毒性实验结果表明 MTX 多相脂质体和 MTX 水溶液的 ivLD_(50)值无显著性差异。亚急性毒性实验表明 MTX 多相脂质体大剂量给药时可出现肝细胞变性坏死。安全性实验未见异常反应。     

小鼠口服多糖包覆胰岛素脂质体的降血糖作用小鼠口服多糖包覆胰岛素脂质体的降血糖作用

目的 研究壳聚糖和海藻酸钠两种多糖包覆胰岛素脂质体的小鼠po降血糖作用。方法 用逆相蒸发法制备胰岛素脂质体;用透射电镜和激光粒度仪测定它们的形态和粒径;用HPLC法和超速离心法测定包封率;用胃蛋白酶和胰蛋白酶溶液试验多糖包覆脂质体对胰岛素的保护作用;用酶-苯酚法测定小鼠po多糖包覆胰岛素脂质体后降血糖作用。结果小鼠po 0.1%壳聚糖和0.1%海藻酸钠包覆的胰岛素脂质体具有较好的降血糖作用。结论壳聚糖或海藻酸钠包覆的脂质体能减少胃蛋白酶或胰蛋白酶对胰岛素的降解并促进胰岛素po吸收。     

油酸多相脂质体注射液(139注射液)

多相脂质体是作为抗癌药物载体的多相分散系新剂型,简称多相脂质体。油酸多相脂质体系由油酸、亚油酸、亚麻酸和花生烯酸等组成,后几种统称为多不饱和脂肪酸,有抗癌作用。实验和临床研究证明,油酸多相脂质体具有淋巴系统定向性.显微放射自显影证明油酸多相脂质体对癌细胞有较高的亲和性。顾学裘     

猕猴桃根多糖脂质体对伊半乳糖胺所致小鼠实验性急性肝损伤的药效作用

目的：研究猕猴桃根多糖（APPS）脂质体对D-半乳糖胺所致小鼠急性肝损伤的保护作用。方法：采用D-半乳糖胺所致小鼠急性肝损伤模型,以联苯双酯为对照药,以小鼠血清中ALT、AST等为指标,评价APPS脂质体的抗急性肝损伤作用。结果：APPS脂质体口服液高剂量（200mg／kg）对D-半乳糖胺所致小鼠急性肝损伤药效作用结果显著（P〈0．05或P％0．01）。低剂量（50mg／kg）对各肝损伤模型的治疗则无显著性意义（P〉0．05）。结论：APPS脂质体口服液对小鼠急性肝损伤有较好的保护作用。     

人参多糖多相脂质体对免疫功能的影响及抗癌作用

以巨噬细胞ＥＡ花环形成率为指标，证明了人参多糖多相脂质体（ＺＭＩ，ＺＭ２）可激活正常或荷瘤小鼠腹腔巨噬细胞ＦＣ受体，将有助于改善机体的免疫功能，增强巨噬细胞对肿瘤的攻击能力．同时还证明，ＺＭ１单用对小鼠Ｓ－１８０肿瘤有轻度抑制作用，作为化疗辅助剂与环磷酰胺、环己基亚硝脲合用有协同作用．与氨甲喋呤合用可明显提高抗癌效果．     

Selective inhibition of the mouse brain Mn-SOD by methylmercury

Changes in mRNA levels, protein contents and enzyme activities for brain Cu,Zn- and Mn-SOD by methylmercury chloride (MMC) administration, were examined, over a period of 12 days in ICR male mice. After subcutaneous administration of MMC (10 mg/kg) to mice, brain mercury content reached a maximum at 2 days and remained at that level for at least 5 days. MMC exposure resulted in a time-dependent decrease in the Mn-SOD activity: the enzyme activity at 5 days after exposure to MMC was about 60% of control level whereas this exposure was without effect on the Cu,Zn-SOD activity, indicating differential sensitivity of SOD isozymes to the metal. However, levels of mRNA and protein synthesis for Mn-SOD were unaffected by MMC administration. The direct effect of MMC on the both SOD activities were further examined with purified enzyme preparations. After each SOD isozyme (10 U) was incubated with 0.2 mM MMC for 24 h at pH 7.8, the enzyme activities for Cu,Zn- and Mn-SOD were 90% and 37% of control, respectively. Incubations at a ratio of SOD to MMC (1 : 600) for 24 h resulted in a substantial decrease in the enzyme activity of the Mn form; this isozyme-selective inactivation was noted at alkaline pH. A combination of isoelectric focusing-agarose gel electrophoresis (IEF-AGE) and synchrotron radiation X-ray fluorescence (SR-XRF) analysis revealed that Mn-SOD rather than Cu,Zn-SOD underwent modification. Furthermore, a decrease in native form of Mn-SOD protein after MMC exposure was confirmed by gel filtration chromatography. These results indicate that Mn-SOD, but not Cu,Zn-SOD, is susceptible to modification by MMC and the resulting alteration in structure appears to cause a loss of enzyme activities.     

多相脂质体139抑制DNA、RNA、蛋白质生物合成机制的初步研究

多相脂质体139能够明显抑制癌细胞 DNA 合成,其抑制~3H—TdR 掺入艾氏腹水癌细咆 DNA 合成的曲线为缓慢递增型,表现为可逆性抑制并具有浓度依赖性。药物剂量为1.0mg/ml 时对 RNA 合成呈现轻度抑制并导致癌细胞核酸含量减少。“139”对S—180鼠肿瘤细胞蛋白质合成作用显著,最高抑制率为67.8%。对 RRL 蛋白质合成抑制率为46.8%,这种抑制作用是在延迟了十分钟后表现出来的,说明反应体系中聚核糖核蛋白体上已经开始合成肽链的核糖核蛋白体仍可继续完成肽链的合成,而新的核糖核蛋白体重新由其亚基组合时则受到一定抑制。“139”对肽酰—~3H—嘌吟霉素结合反应并无抑制作用,故不是转肽抑制剂.     

丝裂霉素C的心肌毒性作用

丝裂霉素C对心肌细胞有明显毒性作用,电子显微镜观察显示小鼠在体心肌细胞肌丝集合体断裂、溶解,细胞核染色质集聚、核膜皱缩等;对体外培养心肌细胞可引起搏动频率减慢、节律失常,乳酸脱氢酶释放增加,严重者细胞停搏甚至固缩或脱落,对心肌细胞的DNA合成也有明显抑制作用。     

转染结构性雄烷受体对丝裂霉素C和5-氮丙啶-3-羟甲基-1-甲基吲哚-4,7-二酮的细胞毒性的影响

研究丝裂霉素C(MMC)及其衍生物5-氮丙啶-3-羟甲基-1-甲基吲哚-4,7-二酮［5-(aziridin-1-yl)-3-hydroxymethyl-1-methylindole-4,7-dione，629］的细胞毒性，以及结构性雄烷受体(constitutive androstane receptor，CAR)转染对其生物学效应的影响。将质粒mCAR/pCR3转染HepG2细胞，经G418耐药性筛选获得转染CAR的g2car细胞，以转染空载体pCR3(HepG2/pCR3)作为对照。用RT-PCR检测质粒和CYP2B6 mRNA的表达，用MTT法评价MMC和629对g2car细胞和HepG2细胞在有氧和乏氧条件下的细胞毒性。RT-PCR检测到CAR和CYP2B6 mRNA在g2car细胞中有表达，在HepG2细胞中无表达；此外，在乏氧情况下，MMC和629的细胞毒性比在有氧情况下均有所增加(p<0.05)，并且转染CAR以后，两者的细胞毒性均增加，但对MMC的影响较明显(p<0.05),对629的影响不明显(p>0.05)。提示CAR可在转录水平调节药物的代谢，提高药物的毒性；CYP2B6可以主要代谢MMC，但不主要代谢629。转染CAR基因可以增加细胞CYP2B6 mRNA的表达，并可引起MMC和629毒性的改变。     

Comparison of neurobehavioral changes in three inbred strains of mice prenatally exposed to methylmercury

Pregnant mice of three inbred strains (BALB/c, C57BL/6J, C57BL/6Cr) were orally given methylmercury (MMC; 3 x 3 mg/kg body weight) or the equivalent volume of phosphate-buffered saline during days 12-14 of gestation and allowed to deliver. The behaviors of their male offspring were evaluated in an open field and their home cage and in a Morris water maze. In the open field test, the BALB/c and C57BL/6Cr MMC groups exhibited less total locomotor activity than did their respective control groups. However, there was no significant difference observed between the MMC and control C57BL/6J strain. In the BALB/c strain, the MMC group exhibited significantly more central locomotion and significantly less peripheral locomotion than did the control group. These results indicated that the prenatal exposure to MMC caused decreases in open-field activity in the C57BL/6Cr and BALB/c strains, concomitantly with a change in emotional status in BALB/c strain. For spontaneous activity in their home cage, all groups moved more actively in the dark phase than in the light phase except BALB/c MMC group. The BALB/c MMC group moved in the light phase as much as in the dark phase, indicating a disturbance of nocturnal rhythm of spontaneous activity. In the Morris water maze, the C57BL/6Cr and C57BL/6J control groups perform very well over the 5 consecutive days. The prenatal exposure to MMC caused significantly prolonged latency in the C57BL/6Cr and C57BL/6J, but not in BALB/c strain. This result indicated that the prenatal exposure to MMC impaired the performance in the Morris water maze differently among the strains. This study provides a basis for evaluating strain-specific neurobehavioral changes when the widely used three inbred strains of mice are chronically exposed to MMC.     

中药桔梗对丝裂霉素诱发小鼠骨髓微核率的影响

[摘 要] 目的：观察中草药桔梗对丝裂霉素（MMC）诱发小鼠微核的抑制作用。方法： 50只小鼠随机分为阴性对照组（N?S）,阳性对照组（MMC,30mg? kg-1）;桔梗水煎液诱变组（1.0、2.0、4.0和8.0 g?kg-1 ,相当于人5×、10×、20×、40×临床常用剂量）; 桔梗水煎液抗诱变组（MMC 0.4mg?kg-1＋桔梗各剂量组）。每组5只动物,雌雄兼用。MMC腹腔注射给药,其他药物均为灌胃给药,抗诱变实验组桔梗和MMC同时给药,小鼠骨髓嗜多染红细胞微核实验按常规方法进行。结果： 桔梗各剂量组所诱导的小鼠微核频率与正常对照组比较,差异无显著性(P>0.05)。桔梗本身不能诱发小鼠微核,并且4.0g.kg-1,8.0g.kg-1组与丝裂霉素一同给药时,可使丝裂霉素所诱发的小鼠微核率明显降低(P＜0.05)。结论：桔梗对遗传物质无诱变作用,对小鼠遗传物质具有一定的保护作用。     

姜黄素改善丝裂霉素C导致的肾功能损伤

目的 探讨姜黄素对丝裂霉素C(MMC)导致的肾功能损伤的影响及作用机制.方法 制备人乳腺癌异种移植瘤裸鼠模型,2周后分别ip给予姜黄素100 mg·kg<'-1>,隔天1次,MMC 1,1.5和2 mg·kg<'-1>,隔5 d 1次;姜黄素+MMC组各药的剂量与频率与单独用药一致,实验持续4周.观察动物体质量和存活率...     

Fusogenic liposome can be used as an effective vaccine carrier for peptide vaccination to induce cytotoxic T lymphocyte (CTL) response

We reported previously that fusogenic liposome (FL) introduced antigen protein encapsulated in the liposome directly into the cytoplasm of the antigen presenting cells, and that it induced immune responses. In the present study, we encapsulated TAX38-46, an HTLV-I derived protein and an antigen peptide model, into FL. The ability to induce effective cytotoxic T lymphocytes (CTL) responses in immunized mice was evaluated. Results showed FL could induce CTL response effectively and suggested that FL is a potential peptide vaccine carrier.     

天花粉蛋白抗结肠癌体内实验研究

本研究以人结肠癌SW－1116细胞体外培养后移植于Swiss－DF品系8周龄裸鼠双侧肾包膜下，次日以不同剂量天花粉蛋白（Trichosanthin，TCS）注射入裸鼠腹膜腔内。每天1次，连续5d，d8解剖裸鼠，观察天花粉蛋白对移植瘤体内抑制情况。结果显示：TCS剂量为0．75mg／kg组抑瘤率为41．2％（P＜0．01），优于丝裂霉素组（抑瘤率31．28％）0．5mg／kg组抑瘤率为27．5％（P＜0．05），远小于TCS对小鼠的半数致死量LD50（134mg／kg）。提示TCS体内应用安全度大，临床研究前景好。     

黄芪多糖对丝裂霉素C(MMC)致骨髓抑制小鼠骨髓及脾脏造血祖细胞的生成作用的影响

目的　研究黄芪多糖 (APS)对MMC致骨髓抑制小鼠的骨髓和脾造血祖细胞生长的影响。方法　d 0腹腔注射丝裂霉素C(MMC) 7mg·kg- 1 ,APS皮下注射 1 0 0mg·kg- 1·d- 1 ,给药方案分 3种 :① 0～ 4d ,共 5d ;② 0～ 1 1d ,共 1 2d ;③ 1 2d给药 ,3wk内给完 ,用造血细胞集落培养法观察APS的药理作用。结果　在d 3时 ,APS治疗组对MMC致骨髓抑制小鼠骨髓CFU C数目增加了 3倍 ,分别为 1 870±40 /股骨和 62 4 0± 1 1 0 /股骨 ,从d 3～d 1 8,APS治疗组的骨髓CFU C均高于模型组。在给MMC后d 1 4之前APS对脾CFU C的生长没有影响 ,APS在d 1 4和d 1 8时APS有刺激脾造血祖细胞增殖作用 (分别高 3倍和 2倍 )。结论　APS对MMC引起骨髓抑制小鼠有促进骨髓和脾脏造血祖细胞的增殖和成熟的作用