厄贝沙坦对自发性高血压大鼠的降压作用及肾脏RAS基因表达分析

Effect of Irbesartan on blood pressure of spontaneously hypertensive rats and analysis of renal RAS gene expression

目的探讨厄贝沙坦对自发性高血压大鼠(SHR)的降压作用及其对肾脏肾素-血管紧张素系统(RAS)相关基因表达的影响。方法将SHR大鼠随机分为模型组[15 mg/(kg·d),饮用水]、厄贝沙坦组[15 mg/(kg·d),厄贝沙坦],每组6只;另设6只Wistar大鼠为正常对照组[15 mg/(kg·d),饮用水],各组均给药8周。无创血压仪测量各周大鼠给药3 h及24 h血压变化;RT-qPCR检测肾组织中血管紧张素转化酶2(ACE2)、血管紧张素Ⅱ受体-1(AT1R)、AT2R mRNA的表达情况。结果厄贝沙坦组与模型组大鼠收缩压(SBP)给药后3 h和24 h组间比较,差异有高度统计学意义(P<0.01)。其中厄贝沙坦组SBP首次给药,第2、4、6、8周给药后3 h及24 h低于模型组,差异有统计学意义(P<0.05或P<0.01)。厄贝沙坦组与模型组大鼠舒张压(DBP)给药后3 h和24 h组间比较,差异有高度统计学意义(P<0.01)。其中厄贝沙坦组DBP首次给药后3 h低于模型组,第2、4、6、8周给药后3 h及24 h低于模型组,差异有统计学意义(P<0.05或P<0.01)。与模型组比较,厄贝沙坦组ACE2 mRNA相对表达量降低,AT2R mRNA相对表达量升高,差异有统计学意义(P<0.05)。结论厄贝沙坦具有显著降血压作用,厄贝沙坦使血压降低后,机体产生血压调节的保护作用,使ACE2表达降低。且AT1R和AT2R在血压调节中存在功能性相互作用,AT1R阻断后降低血压,并可能导致对立的AT2R的刺激升高作用。

Objective To explore the effect of Irbesartan on blood pressure of spontaneously hypertensive rats(SHR)and the influence on renal Renin-angiotensin system(RAS)related gene expression.Methods The SHR rats were randomly divided into model group(15 mg/[kg·d],drinking water),Irbesartan group(15 mg/[kg·d],Irbesartan),six rats in each group;another six Wistar rats were served as normal control group(15 mg/[kg·d],drinking water)and each group was administered for eight weeks.The blood pressure changes of rats at three hours and 24 h after administration of each week were measured by the non-invasive blood pressure meter;RT-qPCR was used to detect the expression of angiotensin converting enzyme 2(ACE2),angiotensinⅡreceptor-1(AT1R)and AT2R mRNA in kidney tissue.Results The systolic blood pressure(SBP)of the Irbesartan group and model group at three hours and 24 h after administration showed highly statistically significant difference(P<0.01).Among them,SBP in the Irbesartan group was lower than that in the model group at three hours and 24 h after administration at the first time,two,four,six and eight weeks,and the differences were statistically significant(P<0.05 or P<0.01).The difference in diastolic blood pressure(DBP)between the Irbesartan group and model group at three hours and 24 h after administration was highly statistically significant(P<0.01).Among them,the DBP of the Irbesartan group was lower than that of the model group three hours after administration at the first time,while were lower than those of the model group at three hours and 24 h after administration at two,four,six,and eight,and the differences were statistically significant(P<0.05 or P<0.01).Compared with the model group,the relative expression of ACE2 mRNA in the Irbesartan group was decreased,while the relative expression of AT2R mRNA was increased,and the differences were statistically significant(P<0.05).Conclusion Irbesartan has a significant effect on lowering blood pressure.After Irbesartan reduces blood pressure,the body produces a protective effect of blood pressure regulation,so that the expression of ACE2 is reduced.Moreover,AT1R and AT2R have a functional interaction in blood pressure regulation.Blocking AT1R reduces blood pressure,and may lead to the stimulating and elevating effect of opposite AT2R.