自发性高血压大鼠口服托特罗定的中长期耐受性研究

目的：探索自发性良性前列腺增生大鼠模型（f1发性高疵压大鼠，SHR）门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纽，其中3组每组6只，分别给予托特罗定4．2rag／（kg·d）、5．3mR／（kg·d）、7mg／（kg·d）。以生理盐水配成悬液分两次灌胃给药，给药容量为1．5ml／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．灌胃期问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；低剂壁组日均进食、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，但足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。

Medium-and-Long-Term Tolerance of Tolterodine to Spontaneous Hypertension Rats

Objective.. To study the medium-and-long-term tolerance of tolterodine to spontaneous hypertension rats（SHR）. Methods ： Twenty male SHR aged 13 weeks were randomly assigned into 4 groups： three experimental groups（six SHRs each） were taken tolterodine orally of 4.2 mg/（kg · d）.5. 3 mg/（kg · d） .7 mg/（kg · d）; respectively, drug were dissolved in physiological saline and intragastrically administrated twice a day; the control group（two SHRs） were received the same volume physiological saline. All rats were intragastrically administrated for four weeks. The general state of health of SHRs, such as activity, food-intake amount; water-intake amount, weight growth, etc, were observed during the experiment, and the structure and function of major organs were tested after experiment. Results：During the experiment, no SHRs died because of intragastric administration, and SHRs in each groups behaved normally. The average body weight growth of SHRs in each experimental group every week had no difference when compared with the control group, but among the experimental groups, the lowdose group had higher average body weight than the mid-dose group （P〈0. 05）. The mean food-intake amount and water-intake amount of the low-dose group were more than the control group and the other two experimental groups （p〈0. 01）. The histopathology of main organs of all groups had no significant difference when compared each other, but the ratios of liver weight/body weight of the mid-dose and high-dose experimental groups were decreaced when compared to the control group（both P〈0. 05）. The biochemistry examination showed that the average serum CREA level and UREA level of each experimental groups were lower than the control group （both P〈 0.05）, and ALT, AST, ALB, TB or UA level were similar to control group. Conclusions：SHRs have a quite good medium-and-long-term tolerance to tolterodine.