阿霉素注射次数及剂量对肾病综合征模型的影响

目的：建立阿霉素（ADR）大鼠肾病综合征模型,探讨相关影响因素,考察阿霉素的给药剂量与造模方法（一次性注射和分次注射）,确立造模的最佳条件。方法：利用尾静脉一次性注射和分次注射阿霉素,构建大鼠肾病综合征动物模型。结果：阿霉素造模后大部分出现尿蛋白排出量增加、精神不佳等现象。B组（一次性尾静脉注射ADR7.5mg/kg）死亡率66.7%,C组（分二次尾静脉注射ADR,共7.5mg/kg）,D组（一次性尾静脉注射ADR6mg/kg）死亡率25%;F组（一次性尾静脉注射ADR5mg/kg）,尿蛋白含量相对于其他几组偏低;E组（分二次尾静脉注射ADR,共6mg/kg）大鼠精神状态良好,能较快时间达到较高的尿蛋白含量（〉250mg/24h）;病理切片显示E组出现肾小球局灶节段性硬化和节段性纤维素样坏死。结论：从精神状态、尿蛋白含量、死亡率、病理切片等综合比较,尾静脉注射ADR4mg/kg,1周后再注射2mg/kg,4周后可以高效地复制出阿霉素肾病综合征大鼠模型。     

EAP／LF交替方案治疗进展期胃癌的临床研究

目的：探讨EAP／LF交替方案进展胃癌的疗效。方法：自1994年10月至1999年12月，124例经病理确诊的有可测量病灶的进展期胃癌患者被随机分入EAP／LF组（研究组）和EAP组（对照组），研究组用药为：足叶乙甙（Vp-16)70mg/m^2，静滴，d4-6；阿霉素（ADM）15mg/m^2，静注d1.7；顺铂（DDP）20mg/m^2，静滴，d2．8，醛氢叶酸（CF）70mg/m^2，静滴，d29－33，5－氟尿嘧啶（5－FU）325mg/m^2，静滴，d29－33，每8周重复，。结果：研究组客观有效率为62．1％，明显优于对照组的48．3％（P＝0．032）；研究组有效者中位生存期、无进展生存时间分别为20个月、13个月，均明显优于对照组13个月（P＝0．037）、7个月（P＝0．007）。两组不良反应主要有白细胞减少、口腔粘膜炎、脱发、结论：调整剂量的EAP／LF交替方案是一疗效确切，安全、对生存有益处的治疗进展期胃癌的优势方案，值得临床进一步研究。     

P波最大时间P波离散度预测阿霉素引起房性心律失常的价值

目的 探讨P波最大时间P波离散度预测阿霉素引起房性心律失常的关系。方法 回顾分析了130例肿瘤患使用阿霉素前，同步12导联心电图的P波最大时间P波离散度。结果 观察组70例，用药前P波最大时间及离散度均明显大于对照组60例（P＜0．01）。以及两相结合对使用阿霉素后发生房性心律失常的敏感性为70．0％，特异性为90．0％，准确性为79．2％。结论 P波最大时间≥110ms,P波离散度≥40ms，是预测使用阿霉素后发生房性心律失常的体表心电图指标。     

阿霉素磁液术前靶向化疗对进展期胃癌细胞凋亡和增殖的影响

目的 研究进展期胃癌术前给予阿霉素磁液靶向化疗后，胃癌组织中细胞凋亡与增殖状态的变化。方法 随机选择３０例进展期胃癌，术前２周给予阿霉素磁液靶向化疗，应用脱氧核糖核酸末端转移酶介导的ｄＵＴＰ缺口末端标记法（ＴＵＮＥＬ法）和增殖细胞核抗原（ＰＣＮＡ）免疫组织化学染色法，分别检测化疗前后胃癌组织及癌周正常粘膜组织中细胞凋亡指数（ＡＩ）与增殖细胞核抗原的指数（ＰＩ）。结果 术前阿霉素磁液化疗对正常粘膜组     

Determination of the Thickness of the Fixed Aqueous Layer Around Polyethyleneglycol-coated Liposomes

Abstract

The zeta potentials of adriamycin-encapsulating liposomes containing 1-(monomethoxy polyethyl-eneglycol)-2,3-dimyristoylglycerol (PEG-DMG) were measured in an isotonic solution of 10mM lactate buffer (pH 4.0) with sodium chloride and sucrose. The negativity of the zeta potentials of adriamycin-encapsulating liposomes containing PEG-DMG decreased with increases in NaCl concentration more steeply than that of adriamycin-encapsulating liposomes without PEG coating. From this observation, the electrical potential distributions near the membrane surfaces were shown to be different between adriamycin-encapsulating liposomes with and without PEG coating. Based on these zeta potential data, the thickness of the fixed aqueous layer around PEG-DMG-containing adriamycin liposomes was determined from the slope of In zeta potential versus Debye-Hiickel parameter plot. As a result, a correlation was indicated to exist between the circulation time of liposomes and the thickness of the aqueous layer around the liposomes.     

肝动脉注射阿霉素温度敏感脂质体的制剂研究

自Yatvin等创造温度敏感脂质体以来,许多研究结果证明它是靶治疗的良好载体。Chuang等认为根据荷瘤肝脏的血流分布,设想将温度敏感脂质体通过肝动脉注射滞留于肝动脉,结合人为控制释放脂质体中所包封的药物,有可能提高肝脏肿瘤中的药物浓     

阿霉素磁性蛋白微球的改良法制备

目的　采用改良方法自行制备抗肿瘤药物阿霉素磁性蛋白微球 ,为进一步的动物实验和临床应用奠定基础。方法　自行研制改良法 ,制备阿霉素磁性蛋白微球 ,即人体血清白蛋白1 4 0mg、阿霉素 30mg、化学合成磁粉 50mg经精制棉籽油乳化交联混合而成。 结果　改良方法可靠 ,制备的阿霉素磁性蛋白微球形态较理想 ,符合静脉用药。平均直径为 (1 .0 2 0 0± 0 .0 0 94) μm ;形状因子为 :0 .7780± 0 .0 32 2。结论　改良方法可行可靠 ,为阿霉素磁性蛋白微球在以后的动物实验和临床应用上奠定了良好的基础     

肝动脉注射阿霉素温度敏感脂质体的靶行为和治疗应用的研究

Temperature sensitive liposome entrapped adriamycin was injected into the hepatic artery of Wistar rats bearing implanted hepatic tumor. Two hours after the injection, the liver was heated to 42 ℃ and maintained at that temperature for 6 minutes using a local hyperthermia. The variation in the pattern of the concentration of the liposomal drug in circulation, and the drug distribution in tissues were investigated. Results indicated that adriamycin was released from the liposomes with the drug concentration peaking in circulation at 30 minutes after heating. Following the hyperthermia treatment, the total amount of drug in the liver decreased, while that in the tumor and urine increased. The ¹⁴C labeled liposome track test showed that a parallel relationship between the lipid and the drug was maintained for 8 hours after the hepatic injection, and physiological environment was a determinant of change and existence of liposomal carrier. However, the drug encapsulated in the liposomes can be controlled by hyperthermia to target the tumor. Therapeutic experiments showed that in the group treated with the hepatic artery- injected liposome plus hyperthermia control, the liver tumor growth of the rats administered at 7 days after W₂₅₆ carcinosarcoma implantation on liver was notably inhibited and the life-span of the animal was greatly extended compared with those of aqueous administration groups and ⅳ injected liposome group.     

慢性充血性心力衰竭心肾阳虚型大鼠模型的研究

目的 :探讨慢性充血性心力衰竭 (CHF)中心肾阳虚动物模型的制作方法。方法 :72只大鼠随机分为4组 :D、F组切除双侧甲状腺 ,G和 E组进行假切手术 ;手术 1周后 ,D和 E组持续注射阿霉素 (ADR) ,G、F组则注射生理盐水 ,连用 2周。然后比较各组动物外观分值、心肌酶谱、甲状腺激素测定及心脏病理解剖 (包括电镜 )等的差异。结果 :反映虚证的动物外观分值 ,反映肾阳虚的尿量减少和血清甲状腺素水平下降 ,反映心气、心阳受损的心肌酶谱、心功能检测 ,以及病理学检查等指标均以 D组最为突出。“药物反证”可以间接验证 D组模型动物更“接近”CHF中的心肾阳虚证型。结论 :D组动物模型能够较好地模拟 CHF中的心肾阳虚证。