口服三苯双脒抗小鼠横纹肌中旋毛虫成囊期幼虫的疗效评价

发布时间：2018-05-19 03:29

本文选题：旋毛虫病 + 三苯双脒　；参考：《山西医科大学》2014年硕士论文

【摘要】：目的评价口服不同剂量三苯双脒(TBD)和不同疗程口服TBD300mg/(kg-d)抗小鼠横纹肌中旋毛虫成囊期幼虫的疗效,比较口服TBD的三种不同溶液抗小鼠旋毛虫成囊期幼虫的效果。材料与方法实验1：88只小鼠随机均分为11组,每鼠口服感染成囊期幼虫50条。感染后29d,分别口服TBD0-500mg/(kg-d),连服6d。观察小鼠的不良反应。治疗后7d,肌肉压片法计数膈肌、咬肌、胸肌和腓肠肌中成囊期幼虫,以每克肌肉平均幼虫数评价疗效。实验2：40只小鼠随机均分为5组,每鼠口饲感染成囊期幼虫50条。感染后29d,以不同疗程(2、4、6、8d)口服TBD300mg/(kg-d)治疗,对照组不治疗。停药后7d,肌肉压片法计数膈肌、咬肌、胸肌、腓肠肌中幼虫。另40只小鼠随机均分为5组,进行反证实验,分别用上述不同疗程治疗后的小鼠膈肌幼虫50条口饲感染,感染后29d,肌肉压片法计数膈肌中幼虫。实验3：40只小鼠随机均分为4组,每鼠口服感染成囊期幼虫50条。感染后29d,分别用不同溶剂的三苯双脒治疗,溶剂分别为：7%吐温-80和3%乙醇(吐温组),1%羧甲基纤维素和3%乙醇(羧纤组),7%羟丙基-p-环糊精和3%乙醇(羟环组)。剂量均为200mg/(kg-d),连续给药6天,对照组不治疗。治疗后14d,肌肉压片法计数膈肌和腓肠肌的活虫数和死虫数,以每克肌肉平均幼虫数评价疗效。结果实验1：50～300mg组小鼠无药物有不良反应；350和400mg组小鼠有重度不良反应,分别死亡25%和50%；450和500mg组小鼠在给药4～5d全部死亡。50mg组无疗效,随TDB剂量增高,4个部位肌肉的总虫数和活虫数下降,而死虫数升高,其中300mg组4个部位肌肉的活虫数显著少于对照组(P0.01),而350和400mg组4个部位肌肉中幼虫全部死亡(P0.01)。实验2：所有小鼠未见药物不良反应。随疗程天数的增加,4部位肌肉中幼虫总虫荷和活虫数下降,而死虫数升高。与对照组相比,2d及2d以上疗程组膈肌、咬肌和腓肠肌中总虫数和活虫数显著减少(P0.05、P0.01),6d和8d疗程组胸肌总虫数显著减少(P0.05、P0.01)。随着疗程增加,4部位肌肉的幼虫死亡率升高,6d和8d疗程组分别达96.16%～99.13%和99.62%～100%(P0.01)。疗效验证性感染表明,6d(37.5%)和8d(12.5%)的感染率显著低于对照组(100%)和2d(100%)疗程组(P0.01)。实验3：所有小鼠无药物不良反应。与对照组相比,3个治疗组膈肌和腓肠肌中幼虫总虫数和存活虫数均显著减少(P0.05,P0.01),死虫数显著增加(P0.05,P0.01),羟环组的疗效最高。以吐温组TDB的相对药效率为1.0,按减虫率计算,羧纤组对膈肌和腓肠肌中幼虫相对药效率分别为1.61和2.46,羟环组相应为2.13和2.49：而以死虫率计算,羧纤组分别为1.55和1.79,羟环组分别为2.51和2.16(P0.01)。结论口服TBD50mg/(kg-d),给药6天,对肌肉中虫荷无影响。300mg/(kg-d)可有效杀死肌肉中的成囊期幼虫,为适宜剂量。而350mg/(kg-d)或更高剂量TBD对小鼠有毒性作用或致死。口服TBD300mg/(kg-d),连续给药6d或8d,无不良药物反应,可有效杀死肌肉中的成囊期幼虫,连续给药6d为适宜疗程。 3%乙醇加1%羧甲基纤维素或7%羟丙基-β-环糊精配制TBD的相对生物药效率和抗成囊期幼虫效果显著提高,以3%乙醇加7%羟丙基-β-环糊精配制的TBD溶液的效果更佳。
[Abstract]:objective
The efficacy of different doses of three benzamid (TBD) and oral TBD300mg/ (kg-d) oral administration of different doses of TBD300mg/ (kg-d) on the larva of Trichinella Trichinella in mice was evaluated, and the effect of three different solutions of oral administration of orally on mouse Trichinella cysts was compared.
Materials and methods
Experimental 1:88 mice were randomly divided into 11 groups, each mouse was infected with 50 cystocyst larva orally. After infection, 29d, TBD0-500mg/ (kg-d) was taken orally, and the adverse reaction of mice was observed with 6D.. After treatment, 7d was used to count the phrenic, masseter, pectoral and gastrocnemius myocytocyst, and the average number of muscle larvae per gram of muscle was evaluated.
The mice were randomly divided into 5 groups at 2:40 in the experiment. 50 mice were infected by the mouth of each mouse. After infection 29d, TBD300mg/ (kg-d) was taken orally with different courses of treatment (2,4,6,8d), and the control group was not treated. After stopping the drug, the muscles of the diaphragm, the masseter muscle, the pectoral muscle and the gastrocnemius were counted by 7d. The other 40 mice were randomly divided into 5 groups and carried out the reverse experiments, respectively. After treatment, the diaphragm muscles of mice were infected by 50 different ways. After infection, 29d was used to count the larvae in diaphragm.
The mice were randomly divided into 4 groups at 3:40. Each mouse was infected with 50 cystocyst larvae. After infection, 29d was treated with three benzamiprid in different solvents. The solvents were 7% Twain -80 and 3% ethanol (Twain group), 1% carboxymethyl cellulose and 3% ethanol (carboxyl group), 7% hydroxypropyl -p- cyclodextrin and 3% ethanol (hydroxyl group). The dose was 200mg/ (kg- D), after 6 days of continuous administration, the control group was not treated. After the treatment, the number of live worms and the number of dead worms were counted by 14d, and the average number of larva per gram of muscle was evaluated.
Result
The mice in the 350 and 300mg group had no adverse reactions. The 350 and 400mg mice had severe adverse reactions, which died 25% and 50%, respectively. 450 and 500mg mice had no curative effect in all.50mg groups of 4 to 5D, with the increase of TDB dose, the number of total insects and the number of live worms in the 4 parts of the muscles were reduced, and the number of dead insects in the 300mg group was increased, among which the 300mg group 4 parts muscle was muscle. The number of live insects in meat was significantly less than that in the control group (P0.01), while in the 350 and 400mg groups, all the 4 parts of the muscle larvae died (P0.01).
Experiment 2: no adverse drug reaction was found in all mice. With the increase of the duration of the course of treatment, the number of total larvae and live worms in the 4 parts of the muscles decreased, but the number of dead worms increased. Compared with the control group, the number of total worms and the number of live worms in the 2D and 2D groups were significantly reduced (P0.05, P0.01), and the number of the total pectoral muscles in the 6D and 8D courses was significantly reduced. Less (P0.05, P0.01). As the course of treatment increased, the mortality of the 4 muscle larvae increased, and the group of 6D and 8D was 96.16% to 99.13% and 99.62% to 100% respectively (P0.01). The efficacy of confirmatory infection showed that the infection rate of 6D (37.5%) and 8D (12.5%) was significantly lower than that of the control group (100%) and 2D (100%) course group (P0.01).
Experiment 3: All mice had no adverse drug reactions. Compared with the control group, the total number of larvae and the number of surviving worms in the 3 treatment groups were significantly decreased (P0.05, P0.01), the number of dead worms increased significantly (P0.05, P0.01), the effect of the hydroxyl group was the highest. The drug efficiency of the TDB in the Twain group was 1, and the carboxyl fiber group was calculated on the diaphragm and fibula according to the rate of worm reduction. The relative efficacy rates of larva in the intestinal muscle were 1.61 and 2.46, respectively 2.13 and 2.49 in the hydroxyl group, and 1.55 and 1.79 in the carboxyl group and 2.51 and 2.16 in the hydroxyl group (P0.01), respectively.
conclusion
Oral TBD50mg/ (kg-d), for 6 days, did not affect.300mg/ (kg-d) in the muscles of the muscle, which could effectively kill the cyst stage larva in the muscle, which was the appropriate dose. 350mg/ (kg-d) or higher dose TBD had toxic effect or death to mice.
Oral administration of TBD300mg/ (kg-d), continuous administration of 6D or 8D, has no adverse drug reaction, and can effectively kill the cystic stage larvae in muscle. Continuous administration of 6D is an appropriate course of treatment.
The effect of 3% ethanol plus 1% carboxymethyl cellulose or 7% hydroxypropyl - beta cyclodextrin on the relative biologic efficiency of TBD and the effect of anti cystic larva increased significantly, and the effect of TBD solution prepared with 3% ethanol plus 7% hydroxypropyl - beta cyclodextrin was better.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R532.14

【参考文献】