地龙降压蛋白对自发性高血压大鼠血压及血管紧张素Ⅱ含量的影响

Effects of the antihypertensive protein from earthworm on blood pressure and the level of angiotensinⅡ in spontaneously hypertension rats

目的初步探讨地龙降压蛋白对自发性高血压大鼠(spontaneously hypertension rat,SHR)的降压作用及对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)含量的影响。方法应用专利技术从中药地龙中提取地龙降压蛋白,并测定其体外ACE抑制活性。单次静脉注射地龙降压蛋白,颈动脉插管法观察SHR血压的动态变化。选择16周龄SHR32只随机分为SHR模型组、地龙降压蛋白低剂量组、地龙降压蛋白高剂量组、卡托普利组,同时以同源性Wistar大鼠8只作为正常对照组,药物干预28d,用无创尾动脉套袖法测量大鼠血压变化;放射免疫分析法测定大鼠血浆及肾脏局部AngⅡ含量。选择昆明种小鼠60只,以不同剂量腹腔注射给药测定地龙降压蛋白的半数致死量。结果①地龙降压蛋白对ACE的比抑制活力为2.54;②单次及多次给药,地龙降压蛋白均可明显降低SHR血压(P<0.05);③药物干预后,与SHR模型组比较,地龙降压蛋白组血浆AngⅡ含量显著降低(P<0.05),而肾脏局部AngⅡ虽有所下降,但差异无统计学意义(P>0.05);④地龙降压蛋白对昆明小鼠的半数致死量>20g/kg。结论地龙降压蛋白对SHR有降压作用,其降压机制可能与降低血浆及肾脏局部组织中AngⅡ含量有关。

Objective To investigate the effects of the antihypertensive protein from earthworm on blood pressurea and the level angiotensin Ⅱ in spontaneously hypertension rats（SHR）. Methods ① To isolate and purify the antihypertensive protein from earthworm and measure its action of inhibiting angiotensin conver- ting enzyme （ACE） in vitro; ②to investigate the antihypertensive effect of the antihypertensive protein from earthworm in spontaneously hypertension rats by single intravenous injection and repeated intraperitoneal injection; ③to detecte the change in level of angiotensin Ⅱ ;④ to measure the median lethal dose （LD50） of anti-hypertensive protein from earthworm on mice by intravenous injection. Results ①The specific activity to ACE of the anfihypertensive protein from earthworm was 2. 54 ;②the antihypertensive protein from earthworm could reduce the blood pressure in SHR significantly by single intravenous injection or by repeated intraperitoneal in-jection（ P 〈 0. 05 ）;③the antihypertensive protein from earthworm could lower the angiotensin Ⅱ level in plasma, with a significant difference compared with the model group （ P 〈 0. 05 ）, and lower the angiotensin Ⅱ level in tissue of kidney without a significant difference （ P 〉 0. 05 ） ;④the LD50 of the antihypertensive protein from earthwormwas more than 20 g/kg by intraperitoneal injection. Conclusion The antihypertensive protein from earthworm has a significant effect of decreasing blood presure on SHR. The mechanism may be related to its action in reducing angiotensin Ⅱ levels in plasma and in tissue of kidney.