自发性高血压大鼠尿微量白蛋白、β2-微球蛋白及循环、局部血管紧张素Ⅱ浓度与针箭颗粒的干预

Concentrations of urinary microalbumin and beta_2-microglobulin,circular and local angiotensin Ⅱ in spontaneously hypertensive rats and the intervention of Zhenjian granule

目的:通过观察针箭颗粒对自发性高血压大鼠尿微量白蛋白、β2-微球蛋白及循环、局部血管紧张素Ⅱ浓度的影响,探讨针箭颗粒对自发性高血压大鼠早期肾损害的干预作用。方法:实验于1998-10/1999-01在南京中医药大学第一附属医院临床研究所完成。选择12周龄自发性高血压大鼠40只,随机分为5组,针箭颗粒高、中、低剂量组、卡托普利组及模型组每组8只,分别以11.35,4.54和2.27g/kg的针箭颗粒混悬液(由鬼针草、鬼箭羽、玄参、泽泻等组成,委托江阴天江制药厂生产)、40mg/kg的卡托普利混悬液及同等体积生理盐水灌胃,均为2mL,1次/d。另取Wistar-Kyoto大鼠6只作为正常对照组,以2mL生理盐水灌胃,1次/d。各组大鼠均给药8周。治疗8周后应用尾容积法以HX-Ⅱ型小动物血压测量器测量各组大鼠的尾动脉收缩压,应用放免法测定反应各组大鼠肾脏损害指标的尿微量白蛋白、β2-微球蛋白及循环和局部血管紧张素Ⅱ浓度,并进行各组间比较。结果:高剂量组、模型组各有1只大鼠因感染死亡,模型组另有1只因灌胃意外死亡,进入结果分析针箭颗粒高、中、低剂量组、卡托普利组、模型组和正常对照组分别为7,8,8,8,6和6只。①给药前自发性高血压大鼠各组血压均显著高于正常对照大鼠(q=4.12～5.96,P<0.01),给药后针箭颗粒各剂量组及卡托普利组血压较给药前均明显下降(t=2.46～3.40,P<0.05或P<0.01)。②给药前各组高血压大鼠尿微量白蛋白、β2-微球蛋白均高于正常组(q=2.19～7.30,P<0.01～0.05)。给药后针箭颗粒各剂量组及卡托普利组的β2-微球蛋白均显著低于模型组(q=5.60～7.10,P<0.01),针箭颗粒各剂量组及卡托普利组的尿微量白蛋白亦有不同程度的下降。③肾脏局部血管紧张素Ⅱ浓度模型组显著高于正常组(q=4.86,P<0.01),高剂量组、卡托普利组肾脏血管紧张素Ⅱ浓度明显低于模型组(q=5.63,5.98,P<0.01)。④尿微量白蛋白变化与收缩压及肾脏血管紧张素Ⅱ成明显正相关(r=0.434,0.501,P<0.05),与循环血管紧张素Ⅱ无相关性(r=0.102,P>0.05);尿β2-微球蛋白与收缩压及循环血管紧张素Ⅱ、肾脏血管紧张素Ⅱ均存在明显正相关(r=0.542,0.210,0.674,P<0.01～0.05)。结论:针箭颗粒在降低自发性高血压大鼠血压的同时,可降低反映早期肾脏损害的指标尿微量白蛋白、β2-微球蛋白含量,同时可降低自发性高血压大鼠肾脏局部肾素血管紧张素系统的活性,提示其在一定程度上可以改善早期肾脏损害。

AIM:To observe the effect of Zhenjian granule on the concentrations of microalbumin and beta2-microglobulin in urine,and the circular and local concentrations of angiotensin Ⅱ in spontaneously hypertensive rats,and investigate the interventional effects of Zhenjian granule on the early renal damage in spontaneously hypertensive rats.METHODS:The experiment was carried out in the Clinical Institute of the First Affiliated Hospital,Nanjing University of Traditional Chinese Medicine from October 1998 to January 1999.Forty 12 week old spontaneously hypertensive rats were randomly divided into 5 groups with 8 rats in each group: Zhenjian granule high,middle and low dose groups,captopril group and model group,the rats in each group were treated with gastric perfusion of 11.35,4.54 and 2.27 g/kg Zhenjian granule suspension(which was composed by beggarticks,winged euony twigs,scrophularia root,oriental waterplantain rhizome,etc.,and produced by Jiangyin Tianjiang Parmaceutical Factory),40 mg/kg captopril suspension and saline of the same volume (2 mL),once a day;Another 6 Wistar Kyoto rats were taken as normal controls,which received gastric perfusion of 2 mL saline,once a day;All the rats were treated for 8 weeks.Eight weeks after treatment,the systolic pressure of caudal artery of the rats in each group was measured with the HX Ⅱ type blood pressure schistometer for small animals by means of caudal volumetry,the indexes of renal damage,such as the concentrations of microalbumin and beta2 microglobin in urine,and the concentrations of circular and local angiotensin Ⅱ of rats in each reaction group were determined with radioimmunoassay,and the results were compared among the groups.RESULTS:One rat in the high dose group and model group died respectively because of infection,another one rat in the model group died accidentally for gastric perfusion;There were 7,8,8,8,6 and 6 rats in the Zhenjian granule high,middle and low dose groups,captopril group,model group and normal control group respectively were involved in the analysis of results.① Before administration,the blood pressure was significantly higher in the spontaneously hypertensive rats than in the normal control rats(q=4.12 to 5.96,P< 0.01);After administration,the blood pressure was obviously decreased in the Zhenjian granule groups and captopril group as compared with before administration(t=2.46 to 3.40,P< 0.05 or P< 0.01).② Before administration,the concentrations of microalbumin and beta2 microglobin in urine of the spontaneously hypertensive rats were higher than those in the control group(q=2.19 to 7.30,P< 0.01 to 0.05);After administration,the concentration of beta2 microglobin was significantly lower in the Zhenjian granule groups and captopril group than in the model group(q=5.60 to 7.10,P< 0.01);Microalbumin in urine was decreased to different degree in the Zhenjian granule groups and captopril group.③ The concentration of local angiotensin Ⅱ in kidney was significantly higher in the model group than in the normal group(q=4.86,P< 0.01),but obviously lower in the high dose group and captopril group than in the model group(q=5.63,5.98,P< 0.01).④ The changes of microalbumin in urine was obviously and positively correlated with systolic pressure and angiotensin Ⅱ in kidney(r=0.434,0.501,P< 0.05),but had no correlation with circular angiotensin Ⅱ (r=0.102,P >0.05);Beta2 microglobin had marked positive correlation with systolic pressure,circular angiotensin Ⅱ and angiotensin Ⅱ in kidney(r=0.542,0.210,0.674,P< 0.01 to 0.05).CONCLUSION:Zhenjian granule decreases the blood pressure of spontaneously hypertensive rats,it also can decrease the contents of microalbumin and beta2 microglobin in urine, which reflected the indexes of early renal damage,it plays a role in reducing the activities of local rennin angiotensin system in spontaneously hypertensive rats,which indicates that Zhenjian granule can ameliorate early renal damage to a certain degree.