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目的观察Beagle犬连续6个月po单硝酸异山梨酯、缬沙坦、螺内酯复方(ISMN-V-S)降压药物所产生的毒性反应,比较3种药物联合应用后,毒性是否增加或产生新的毒性。方法健康Beagle犬40只,雌雄各半,分为5组,空白对照组、单缬螺复方15、50、150 mg/(kg·d)及缬沙坦对照组,每组8只动物。给药体积为5 mL/kg,每日ig给药1次,每周给药6 d,连续给药26周,停药观察4周。实验期间,每日进行一般状态观察,每周测定1次体质量及摄食量,并于给药前、给药第13、26周及停药恢复期第4周,分别对眼科、体温、尿常规、心电图、血液学及血液生化学进行检查,在给药期结束前及恢复期结束前测量动物血压,末次给药后及恢复期结束后分两批对动物剖检并进行病理组织学检查。结果各组动物行为活动、饮食、饮水正常。动物体质量、摄食量组间无差异。试验进行过程中进行的眼科、体温、尿常规、心电图、血液学及血液生化学等指标的检查,未见异常。各给药组动物血压同空白对照组比较明显降低,停药后恢复正常。组织病理学检查,除个别动物肾脏发生自发性病变,其他动物未见明显病理器官改变。结论本试验条件下,单缬螺复方降压药物除药理作用延伸引起的血压降低外,未出现药物的蓄积现象,同各成分单独使用相比,未见毒性增加或产生新的毒性。
OBJECTIVE To observe the toxic effects of po for isosorbide mononitrate, valsartan and spironolactone (ISMN-VS) antihypertensive drugs for 6 consecutive months in Beagle dogs. To compare whether toxicity increases or new toxicity. Methods Forty healthy Beagle dogs were divided into five groups according to sex, male and female, respectively. The blank control group, single-valerian compound 15,50,150 mg / (kg · d) and valsartan control group, 8 animals in each group. Administered volume of 5 mL / kg, once daily ig administration, weekly dosing 6 d, continuous administration of 26 weeks, withdrawal observed for 4 weeks. During the experiment, the daily state of general observation, weekly determination of body weight and food intake, and before the administration, the administration of 13,26 weeks and the withdrawal of the first 4 weeks, respectively, ophthalmology, body temperature, urine Blood pressure was measured routinely, electrocardiogram, hematology and blood biochemistry, and blood pressure was measured before the end of the administration period and before the end of the recovery period. After the last administration and at the end of the recovery period, the animals were divided into two groups for histopathological examination . Results The animals in each group were active, eating and drinking normally. Animal body weight, food intake between groups no difference. Ophthalmology, body temperature, urine routine, electrocardiogram, hematology and blood biochemistry and other indicators of the test conducted during the test, no abnormalities. The blood pressure of each administration group was significantly lower than that of the blank control group, and returned to normal after stopping the treatment. Histopathological examination, in addition to an individual animal kidney spontaneous disease, other animals showed no significant pathological changes. Conclusion Under the conditions of this test, the single valerian compound antihypertensive drugs in addition to pharmacological effects caused by the extension of blood pressure, there is no accumulation of drugs, compared with each component alone, no toxicity or new toxicity.