滋肺阴合补肝肾法对阴虚阳亢型肾性高血压大鼠收缩压、内皮素-1及血管紧张素Ⅱ的影响

Effect of Method of Nourishing Yin and Tonifying Liver and Kidney on Contractive Pressure,ET-1 and ANG Ⅱ in Renal Hypertension Rats with Syndrome of Yin Deficiency Leading to Yang Hyperactivity

目的:探讨滋肺阴合补肝肾法对阴虚阳亢型肾性高血压大鼠(RHR)的降压机制。方法:筛选2月龄健康雄性SD大鼠78只,随机分为假手术组13只与手术组65只。手术组通过结扎左侧肾动脉的方法建立肾性高血压模型,以尾套法测血压筛选高血压大鼠,成功模型再给予附子汤4周,并每隔1天激惹大鼠使其打斗,制备阴虚阳亢证模型。筛选造模成功的阴虚阳亢证RHR,随机分为模型组、卡托普利组、滋肺阴组、补肝肾组、滋肺阴合补肝肾组(简称综合组)。假手术组与模型组给予等量生理盐水,用药组每日晨8时灌胃给药1次,连续4周。末次给药24 h后测血压,腹主动脉取血8 mL,制备血清和血浆。ELISA法测定血浆ET-1、ANGⅡ的浓度。结果:各治疗组阴虚阳亢型RHR血压的变化①基础血压:模型组、卡托普利组、滋肺阴组、补肝肾组、综合组血压与假手术组比较均无统计学意义(P>0.05)。②手术后第2周末血压:与假手术组比较,模型组、卡托普利组、滋肺阴组、补肝肾组、综合组血压均明显增高(P<0.05)。③治疗后各组血压的变化:治疗4周后,与模型组比较,卡托普利组、补肝肾组及综合组血压明显降低(P<0.05),滋肺阴组有所降低但无统计学意义(P>0.05);与滋肺阴组比较,卡托普利组、补肝肾组及综合组明显降低(P<0.05);与卡托普利组比较,综合组明显降低(P<0.05),补肝肾组无统计学意义(P>0.05)。滋肺阴合补肝肾法对阴虚阳亢型RHR血浆ANGⅡ、ET-1及血清NO的影响①与假手术组比较,模型组血浆ANGⅡ、ET-1均明显升高(P<0.05)。②与模型组比较,卡托普利组、补肝肾组及综合组血浆ANGⅡ、ET-1明显降低(P<0.05);滋肺阴组血浆ANGⅡ、ET-1有降低,但无统计学意义(P>0.05)。③与滋肺阴组比较,卡托普利组、补肝肾组及综合组有统计学意义(P<0.05);④与卡托普利组比较,综合组血浆ANGⅡ、ET-1明显降低(P<0.05),补肝肾组无统计学意义(P>0.05)。结论:滋肺阴合补肝肾法对阴虚阳亢型RHR的降压机制在于:减少缩血管ET-1的形成,削弱ET所致心肌收缩力增强、心排量增大及血管壁增厚;减少ANGⅡ形成,对抗ANGⅡ所致血管收缩、血管壁增厚及顺应性降低。

Objective ： To investigate the mechanism of method of nourishing yin and tonifying liver and kidney on renal hypertension rats with syndrome of yin deficiency leading to yang hyperactivity. Methods： 78 selected healthy male SD rats aged 2 months were randomly divided into sham operation group （ 13 rats） and operation group （65 rats）. In operation group the models of renal hypertension were made up by ligation of the left renal ar- tery, and among them the hypertensive rats were screened by method of tail cuff to measure blood pressure. Then Aconite Decoction was given to them for 4 weeks, and every one day they were provoked to fight in order to pre- pare the models with syndrome of yin deficiency leading to yang hyperactivity. The successful models of RHR with syndrome of yin deficiency leading to yang hyperactivity were screened and randomly divided into model group, captopril group, group of nourishing lung yin, group of tonifying liver and kidney, and group of nourishing yin and tonifying liver and kidney （synthetic group）. The medication groups were given to intragastric administration at eight in the morning, and sham operation group and model group were given to equal volume of normal saline. Thecourse of treatment included 4 weeks. After 24h in the last administration the blood pressure was measured, and 8mLblood in abdominal aorta was taken and prepared into serum and plasma. Then the concentrations of ET-1 and an- giotensin II in serum were determined by ELISA method. Results： On blood pressure, ① There were not signifi- cant difference on the basic blood pressure between sham operation group and other groups （including model group, captopril group, group of nourishing lung yin, group of tonifying liver and kidney, and synthetic group （P 〉 0.05 ）.②The second week after operation, the blood pressure increased markedly in each group compared with sham operation group （P 〈 0.05 ）. ③ After 4 weeks＇treatment the blood pressure in captopril group, group of ton- ifying liver and kidney and synthetic group decreased obviously compared with that in model group （ P 〈 0.05 ）, but group of nourishing lung yin did not show statistical significance （ P 〉 0.05 ）. The blood pressure also de- creased in aptopril group, group of tonifying liver and kidney and synthetic group markedly compared with group of nourishing lung yin （P 〈 0. 05 ）. And compared with captopril group the blood pressure cut down remarkably in synthetic group （ P 〈 0.05 ）, but in group of tonifying liver and kidney no significant difference show up （ P 〉 0.05）. On ET-1, ANG II and NO, ①ET-1 and ANG II increased obviously in model group compared with sham operation group （P 〈 0.05 ）.② ET-1 and ANG II decreased markedly in captopril group, group of tonifying liver and kidney and synthetic group compared with model group （ P 〈 0.05 ）. They were cut down too in group of nour- ishing lung yin, but no significant difference showed up （P 〉 0.05 ）. （~）There were significant differences between captopril group, group of tonifying liver and kidney and synthetic group and group of group of nourishing lung yin （P 〈 0.05 ）.③ET-1 and ANG II decreased in synthetic group more than in captopril group （ P 〈 0.05 ）, but in group of tonifying liver and kidney there was no significant differences （P 〉 0.05 ）. Conclusion ： The mechanism of nourishing yin and tonifying liver and kidney on renal hypertension rats with syndrome of yin deficiency leading to yang hyperactivity lies in reducing the formation of vasoconstrictor ET-1, weakening myocardial contractility in- duced by the ET as well as increased cardiac output and vascular wall thickening, reducing the formation of ANG II, against vascular contraction caused by ANG II as well as vessel wall thickening and compliance depressing.