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目的:探索自发性良性前列腺增生大鼠模型(自发性高血压大鼠,SHR)口服托特罗定的中长期耐受性。方法:雄性13周龄SHR大鼠20只,随机分成4组,其中3组每组6只,分别给予托特罗定4.2 mg/(kg·d)、5.3 mg/(kg·d)、7 mg/(kg·d),以生理盐水配成悬液分两次灌胃给药,给药容量为1.5 ml/100g;剩余2只为对照组,给予同样体积的生理盐水,连续灌胃4周。灌胃期间观察大鼠的一般表现、进食、饮水、体重增长等,灌胃结束后检测主要脏器组织结构和功能变化情况。结果:灌胃期间各组大鼠表现正常,未出现药物引起的死亡;低剂量组日均进食、饮水量均较其他组明显增多(P<0.01);各剂量组体重与对照组比较差异无统计学意义,但是两周后低剂量组体重增长较中剂量组快(P<0.05),余各剂量组间比较差异无统计学意义;中、高剂量组肝脏比重较对照组为低(P<0.05),余重要器官比重与对照组比较差异无统计学意义;各剂量组肝功能与对照组相比变化不明显;肾功能水平各剂量组血CREA、UREA水平均对照组为低(P<0.05);各组主要脏器组织切片病理学观察未见异常改变。结论:自发性高血压大鼠口服托特罗定的中长期耐受性良好。
Objective: To explore the long-term and mid-term tolerability of oral administration of tolterodine in a rat model of spontaneous benign prostatic hyperplasia (spontaneous hypertensive rat, SHR). Methods: Twenty male SHR rats of 13 weeks old were randomly divided into 4 groups, 6 in each group, and were given tolterodine 4.2 mg / (kg · d), 5.3 mg / (kg · d), 7 mg / (kg · d). The rats were dosed orally with saline twice a day, and the administration volume was 1.5 ml / 100g. The remaining two rats were given as the same volume of normal saline, week. Gavage during the observation of the general performance of rats, eating, drinking water, weight gain, etc., after the end of gavage to detect changes in major organizational structure and function of organs. Results: During the period of gavage, rats in each group showed normal and no drug-induced death occurred. The daily average intake and water intake of low-dose group were significantly higher than those of other groups (P <0.01). There was no difference between the body weight and control group However, after two weeks, the body weight of the low-dose group was faster than that of the middle-dose group (P <0.05), and there was no significant difference between the other groups (P> 0.05) <0.05). There was no significant difference in the weight of vital organs compared with the control group. The changes of liver function in each dose group were not significantly different from those in the control group. The levels of CREA and UREA in the kidney function group were lower than those in the control group <0.05). No significant changes were observed in histological sections of major organs in each group. Conclusion: Long-term and long-term tolerance of oral tolterodine in spontaneously hypertensive rats is good.