化合物BIM-06抗高血压作用实验研究

Experimental Study on the Antihypertensive Effect of Drug BIM-06

目的:本文主要研究抗高血压药BIM-06对原发性高血压大鼠、醋酸脱氧皮质酮(DOCA)致高血压大鼠以及普通Wistar大鼠血压的影响,以及初步毒性研究。方法:将SHR原发性高血压大鼠、DOCA盐性高血压大鼠及正常血压大鼠分别随机分组,阳性对照组灌胃缬沙坦(20 mg/kg),BIM-06低、中、高剂量组分别按25 mg/kg、50 mg/kg和100 mg/kg灌胃,连续给药7 d,末次给药后监测1 h、3 h、6 h、9 h、12 h、24 h的血压,计算给药前后血压变化。以小鼠能耐受的最大体积(0.4 mL/10 g)给小鼠一次灌胃5 g/kg BIM-06,连续观察14 d。结果:BIM-06对原发性高血压大鼠、DOCA致高血压大鼠降血压效果明显,给药后收缩压最大降幅分别达到(31.00±6.25)mmHg和(24.14±6.57)mmHg,p <0.000 1;BIM-06对正常大鼠血压无明显降压作用,小鼠无死亡案例,而且无不良反应。结论:BIM-06对原发性高血压大鼠及DOCA致高血压大鼠具有良好的降血压作用,对正常大鼠血压无明显影响,对小鼠无明显毒性反应。

Objective:This paper mainly studied the effect of antihypertensive drug BIM-06 on blood pressure in primary hypertensive rats,deoxycorticosterone acetate(DOCA)-induced hypertensive rats,and common Wistar rats,and preliminary toxicity studies.Methods:SHR essential hypertensive rats,DOCA salt hypertensive rats and normotensive rats are randomly divided,the positive control group is infused with valsartan(20 mg/kg),BIM-06 low,medium and high dose groups at 25 mg/kg,50 mg/kg and 100 mg/kg,continuous administration for 7 d,the blood pressure is monitored at 1 h,3 h,6 h,9 h,12 h,24 h after the last dose,and the blood pressure changes before and after administration is calculate.The mice are given 5 g/kg BIM-06 intragastric at the maximum volume(0.4 mL/10 g)that the mice could tolerate for 14 days.Results:BIM-06 has a significant effect on the hypotensive effect of essential hypertensive rats and DOCA-induced hypertensive rats,and the maximum reduction of systolic blood pressure after administration reached(31.00±6.25) mmHg and(24.14±6.57) mmHg,respectively,p < 0.000 1;BIM-06 has no significant antihypertensive effect on normal rat blood pressure,no death in mice,and no adverse reactions.Conclusion:BIM-06 has a good hypotensive effect on essential hypertensive rats and DOCA-induced hypertensive rats,and has no obvious effect on blood pressure in normal rats,and has no obvious toxic reaction to mice.