Li Run-hua, Gao Jin-huan, Wang Si-fei, Pei Yan-jiang, Shen Jin-yan, Yan Ping-mei, Yin Guo-rong
Department of Biology, Taiyuan Normal University, Taiyuan 030031, China.
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2011 Apr 30;29(2):117-21.
To observe the efficacy of oral administration of tribendimidine (TBD) at different dosages against Trichinella spiralis encapsulated larvae in murine striated muscle.
A total of 88 BALB/c mice were divided equally into 11 groups. Each mouse was infected orally with 50 T spiralis encapsulated larvae. At day 29 after infection, TBD was each orally administered to mice of the 11 groups with doses of 0 (control group), 50, 100, 150, 200, 250, 300, 350, 400, 450, and 500 mg/(kg x d), respectively. All mice were administered once a day and lasted for 6d, and untoward drug reactions for mice were observed. Mice were sacrificed at the 7th day after administration of TBD, the encapsulated larvae in diaphragmatic muscle, jugomaxillary muscle, pectoral muscle and gastrocnemius muscle were examined by pellet method, and the total, survival and dead worms were counted. The therapeutic effect was estimated on the basis of average quantity of encapsulated larvae per gram muscle.
During the administration period, no untoward reaction were observed in mice of 50-300 mg/(kg x d) groups. Mice in 350 and 400 mg/(kg x d) groups showed body hair dishevelment, emaciation and food-intake decrease, death rates were 25% and 50%, respectively. All mice in 450 and 500 mg/(kg x d) groups died on day 4 and 5 after TBD administration, respectively. In control group, the highest total burden (per gram) was found in diaphragmatic muscle, followed by jugomaxillary muscle, gastrocnemius muscles and pectoral muscles. TBD at dose of 50 mg/(kg x d) was unable to kill encapsulated larvae. In the rest groups, with the increase of drug dose, the total worm burden and the number of survival worms showed a decreasing trend in four kinds of muscles, and were significantly lower than that of the control group (P < 0.05 or P < 0.01). In 300 mg/(kg x d) group the number of survival worms in diaphragmatic muscle, jugomaxillary muscle, pectoral muscle and gastrocnemius muscle [8.6 +/- 1.7, 2.8 +/- 0.7, 3.9 +/- 0.8, and 0, respectively] were significantly lower than that of the control group [3648.1 +/- 989.2, 1266.4 +/- 812.3, 701.9 +/- 196.4, and 711.6 +/- 34.6] (P < 0.01). All encapsulated larvae in the four kinds of muscle died in 350 and 400 mg/(kg x d) groups. With the increase of TBD dosage, the mortality of encapsulated larvae increased in the muscles, reached up to 98.6%--100% in 300 m (kg x d) group (P < 0.01), and 100% in 350 and 400 mg/(kg x d) groups (P < .01).
Oral tribendimidine administered at 50 mg/(kg x d) to mice for 6 d is unable to reduce worm burden in muscle. Tribendimidine 300 mg/(kg x d) effectively kill encapsulated larvae and is a suitable dose against encapsulated larva stage. However, tribendimidine at doses of 350 mg/(kg x d) and above for 6d is toxic to mice and even causing death.
观察不同剂量的三苯双脒（TBD）口服给药对小鼠横纹肌中旋毛虫包囊幼虫的疗效。
将88只BALB/c小鼠平均分为11组。每只小鼠经口感染50条旋毛虫包囊幼虫。感染后第29天，对11组小鼠分别经口给予TBD，剂量分别为0（对照组）、50、100、150、200、250、300、350、400、450和500mg/（kg·d）。所有小鼠每天给药1次，持续6天，观察小鼠的药物不良反应。在给予TBD后第7天处死小鼠，采用压片法检查膈肌、咬肌、胸肌和腓肠肌中的包囊幼虫，计数总虫数、存活虫数和死亡虫数。根据每克肌肉中包囊幼虫的平均数量评估治疗效果。
给药期间，50 - 300mg/（kg·d）组小鼠未观察到不良反应。350和400mg/（kg·d）组小鼠出现毛发蓬乱、消瘦和进食减少，死亡率分别为25%和50%。450和500mg/（kg·d）组的所有小鼠分别在给予TBD后第4天和第5天死亡。对照组中，膈肌中的总虫负荷（每克）最高，其次是咬肌、腓肠肌和胸肌。50mg/（kg·d）剂量的TBD不能杀死包囊幼虫。在其余组中，随着药物剂量的增加，四种肌肉中的总虫负荷和存活虫数呈下降趋势，且显著低于对照组（P < 0.05或P < 0.01）。300mg/（kg·d）组膈肌、咬肌、胸肌和腓肠肌中的存活虫数[分别为8.6±1.7、2.8±0.7、3.9±0.8和0]显著低于对照组[3648.1±989.2、1266.4±812.3、701.9±196.4和711.6±34.6]（P < 0.01）。350和400mg/（kg·d）组四种肌肉中的所有包囊幼虫均死亡。随着TBD剂量的增加，肌肉中包囊幼虫的死亡率升高，300mg/（kg·d）组达到98.6% - 100%（P < 0.01），350和400mg/（kg·d）组为100%（P < 0.01）。
以每天50mg/（kg·d）的剂量对小鼠口服三苯双脒6天不能减轻肌肉中的虫负荷。300mg/（kg·d）的三苯双脒能有效杀死包囊幼虫，是针对包囊幼虫期的合适剂量。然而，350mg/（kg·d）及以上剂量的三苯双脒连续6天对小鼠有毒性，甚至可导致死亡。
