阿苯达唑壳聚糖微球抗小鼠棘球蚴药效实验研究

发布时间：2018-04-15 03:32

本文选题：阿苯达唑 + 壳聚糖　；参考：《石河子大学》2014年硕士论文

【摘要】：目的:通过与阿苯达唑脂质体、阿苯达唑片比较，评价阿苯达唑壳聚糖微球（ABZ-CS-MPs）经口服后治疗细粒棘球蚴（E.g）病的疗效。方法:雄性昆明小鼠220只，腹腔接种细粒棘球蚴，随机分成空白对照组、模型对照组、口服ABZ-CS-MPs组、口服阿苯达唑脂质体（L-ABZ）组和口服阿苯达唑片剂组，每组20只。治疗组又按口服ABZ37.5mg/(kg·次)、75.0mg/(kg·次)、150.0mg/(kg·次)分成三个剂量组。所有小鼠饲养12周后开始灌胃给药，三次/周（每隔一天），连续治疗12周后解剖。评价药物疗效包括：E.g大体形态观察，囊湿重、囊肿抑制率，E.g病理组织改变，小鼠血液、肝脏中阿苯达唑主要代谢产物阿苯达唑亚砜（ABZSX）浓度。结果： ABZ-CS-MPs组棘球蚴囊混浊、实变或钙化程度较其他治疗组明显。各治疗组棘球蚴囊湿重显著低于对照组(p0.01), ABZ-CS-MPs组囊肿抑制率较其他给药组高。棘球蚴生发层和角质层的破坏程度与血液和肝脏浓度变化较一致。ABZ主要代谢产物阿苯达唑亚砜(ABZSX)的药物浓度：口服ABZ-CS-MPs37.5mg/kg血浆中为(0.28570.0132)μg/ml,肝脏中为(0.32960.0571) μg/g;75mg/kg组血浆中为(0.82760.3914) μg/mL,肝脏中为(0.44850.3088) μg/g;150mg/kg组血浆中为(0.80120.5021) μg/mL,肝脏中为(0.49590.3013) μg/g。较口服阿苯达唑片后10h37.5mg/kg血浆中为(0.27680.0164)μg/mL,肝脏中为(0.04160.0188) μg/g;75mg/kg组血浆中为(0.30560.0172) μg/mL,肝脏中为(0.07130.0442) μg/g;150mg/kg组血浆中为(0.40000.0963) μg/mL,肝脏中为(0.04440.0326) μg/g中药物浓度，均有明显提高(p0.05)。较口服L-ABZ37.5mg/kg血浆中为(0.30890.0289) μg/mL,75mg/kg组血浆中为(0.33950.0315) μg/mL，150mg/kg组血浆中为(0.42740.1489) μg/mL，有明显的提高(p0.05)。口服L-ABZ37.5mg/kg肝脏中为(0.13700.1940) μg/g,75mg/kg为(0.78150.4327) μg/g,150mg/kg中为(0.62980.3409) μg/g，与ABZ-CS-MPs比较，无统计学意义(p0.05)。结论:阿苯达唑壳聚糖微球可明显提高阿苯达唑主要代谢产物阿苯达唑亚砜在血液及肝脏中的浓度，，有望成为治疗包虫病的一种新的剂型。
[Abstract]:Aim: to evaluate the efficacy of Albendazole chitosan microspheres ABZ-CS-MPs in the treatment of E. granulosus by oral administration, compared with albendazole liposome and albendazole tablets.Methods: 220 male Kunming mice were inoculated intraperitoneally with echinococcus granulosus. They were randomly divided into control group, model control group, oral ABZ-CS-MPs group, albendazole liposome L-ABZ group and albendazole tablet group with 20 rats in each group.The treatment group was divided into three dose groups according to oral ABZ37.5mg/(kg 75. 0 mg / kg.All mice were fed for 12 weeks and were given intragastric administration three times a week (every other day, 12 weeks after continuous treatment).The evaluation of drug efficacy included gross morphological observation, wet weight of capsule, inhibition rate of cysts and pathological changes of E. g, and the concentration of albendazole sulfoxide, the main metabolite of albendazole in blood and liver of mice.Results: the degree of hydatid opacification, consolidation or calcification in ABZ-CS-MPs group was significantly higher than that in other treatment groups.The wet weight of hydatid cyst in each treatment group was significantly lower than that in control group (P 0.01), and the inhibition rate of cyst in ABZ-CS-MPs group was higher than that in other groups.The degree of destruction in the germinal layer and cuticle of echinococcus was consistent with the changes of blood and liver concentrations. The drug concentration of ABZ SX, the main metabolite of ABZ, was 0.28570.0132 渭 g / ml in oral ABZ-CS-MPs37.5mg/kg plasma and 0.32960.0571 渭 g / ml in liver, and 0.82760.3914 渭 g / mL in liver / liver group.0.80120.5021 渭 g / mL in plasma and 0.49590.3013 渭 g / g in liver.Compared with albendazole tablets, the plasma levels of 0.27680.0164 渭 g / mL in 10h37.5mg/kg, 0.04160.01888 渭 g / g / kg in liver, 0.30560.0172渭 g / mL in plasma of 75mg / kg group, 0.07130.0442 渭 g / g / kg / kg group and 0.04440.0326渭 g / g / kg group, respectively, significantly increased the drug concentration in plasma (0.40000.0963渭 g / mL) and 0.04440.0326渭 g / mL in liver.Compared with 0.30890.0289 渭 g / mL 75 mg / kg L-ABZ37.5mg/kg plasma, 0.33950.0315 渭 g / mL / kg plasma was 0.42740.1489 渭 g / mL / kg group (P < 0.05).In oral L-ABZ37.5mg/kg liver, 0.13700.1940) 渭 g / g / kg was 0.78150.4327 渭 g / kg, and 0.62980.3409 渭 g / kg in 150 渭 g / kg L-ABZ37.5mg/kg liver. Compared with ABZ-CS-MPs, there was no significant difference (p 0.05).Conclusion: albendazole chitosan microspheres can significantly increase the concentration of albendazole sulfoxide in blood and liver and may become a new dosage form for the treatment of hydatid disease.
【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R532.32

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