天麻芎苓止眩片对自发性高血压大鼠ACE2/Ang(1-7)/Mas轴的影响  

Effect of Tianma Xiongling Zhixuan Tablet on ACE2/Ang(1-7)/Mas Axis in Spontaneously Hypertensive Rats

作　　者：刘林 李弘[3] 任卫琼 李苏[2] 蔺晓源[2] 王宇红[3] 柏正平[1,3] LIU lin;LI Hong;REN Wei-qiong;LI Su;LIN Xiao-yuan;WANG Yu-hong;BAI Zheng-ping(Personnel Department,Hunan Academy of Chinese Medicine,Changsha,410013;Medical Innovation Experiment Center of the First Hospital,Hunan University of Chinese Medicine,Changsha,410007;Science and Technology Innovation Center,Hunan University of Chinese Medicine,Changsha,410208)

机构地区：[1]湖南省中医药研究院人事处,长沙410013 [2]湖南中医药大学第一附属医院医学创新实验中心,长沙410007 [3]湖南中医药大学科技创新中心,长沙410208

出　　处：《中国中西医结合杂志》2022年第5期611-617,共7页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家重大科技专项(No.2019ZX09301-103);中国博士后基金项目(No.2018M632966);湖南省卫健委项目(No.20190960);长沙市杰出创新青年培养(No.kq1802008);湖南中医药大学中医学国内一流建设学科资助(No.2018-2020年)。

摘　　要：目的 探讨天麻芎苓止眩片(TXZT)对自发性高血压大鼠(SHR)血管紧张素转换酶(ACE)2/血管紧张素(Ang,1-7)/Mas轴的调控作用,探讨其防治高血压病的作用机制。方法 50只SHR大鼠随机分为模型组、厄贝沙坦组、TXZT高、中、低剂量组,另取10只WKY大鼠作为正常组,厄贝沙坦组给予厄贝沙坦27 mg/kg灌胃;TXZT高、中、低剂量组分别给予TXZT 2.0、1.0、0.5g/kg灌胃;模型组和正常组分别给予等量蒸馏水灌胃。各组均连续给药4周。测量干预前后大鼠收缩压;ELISA法检测血清中肾素(REN)、醛固酮(ALD)、AngⅡ、ACE2、Ang (1-7)的含量变化;免疫组化法检测主动脉AngⅡ、ACE2蛋白表达;Western Blot法检测主动脉ACE2、Mas蛋白表达;RT-PCR法检测主动脉ACE2、Mas mRNA表达。结果 与正常组比较,模型组各时间收缩压升高,血清REN、ALD、AngⅡ水平、主动脉AngⅡ表达升高,血清ACE2、Ang(1-7)水平、主动脉ACE2、Mas蛋白及mRNA表达降低(P<0.05,P<0.01)。与模型组比较,干预后各组各时间收缩压降低,主动脉ACE2 mRNA表达增加(P<0.05);厄贝沙坦组大鼠血清REN、ALD、AngⅡ水平、主动脉AngⅡ表达降低,血清ACE2、Ang(1-7)水平升高(P<0.05,P<0.01);TXZT高剂量组大鼠血清REN、ALD、AngⅡ水平、主动脉AngⅡ表达降低,血清ACE2、Ang(1-7)水平、主动脉ACE2蛋白、MasmRNA表达升高(P<0.05,P<0.01);TXZT中剂量组血清ALD、AngⅡ水平、主动脉AngⅡ表达降低,血清ACE2、Ang(1-7)水平、主动脉ACE2、Mas蛋白、Mas mRNA表达升高(P<0.05,P<0.01);TXZT低剂量组大鼠血清AngⅡ水平降低(P<0.05)。与厄贝沙坦组比较,TXZT高剂量组给药后第2、4周、TXZT中剂量组给药后各时间、TXZT低剂量组给药后第2、3、4周收缩压升高(P<0.05,P<0.01)。结论 TXZT有明显、持续、稳定的降压作用,调节ACE2/Ang(1-7)/Mas受体轴抑制肾素-血管紧张素-醛固酮系统(RAAS)系统活性可能是其降压效应的重要机制之一。Objective To explore the regulatory effect of Tianma Xiongling Zhixuan Tablets(TXZT) on angiotensin converting enzyme(ACE)2/angiotensin(Ang,1-7)/Mas axis in spontaneously hypertensive rats(SHR),and to explore its mechanism of prevention and treatment of hypertension.Methods Fifty SHR rats were randomly divided into the model group,the Irbesartan group,the high-,medium-,and low dose TXZT groups,and another 10 WKY rats were taken as normal group.Rats in the Irbesartan group were administered with irbesartan(27 mg/kg per day);the rats in high-,medium-and low dose group were administered with TXZT 2.0,1.0 and 0.5 g/kg per day,respectively.Equal volume of distilled water were administered to rats in the model group and normal group.The treatment course for all was 4 weeks.Systolic blood pressure(SBP)were measured before and after intervention.The contents of renin(REN),aldosterone(ALD),Ang Ⅱ,ACE2 and Ang(1-7) in serum were detected by ELISA.The expression of Ang Ⅱ and ACE2 in aorta were detected by immunohistochemistry.The expression of ACE2 and Mas in aorta were detected by Western Blot.The ACE2 and Mas mRNA expression in aorta were detected by RT-PCR.Results Compared with the normal group,SBP of the model group increased at each time point,the levels of REN,ALD and Ang Ⅱ in serum and the expression of Ang Ⅱ in aorta increased,while the levels of ACE2 and Ang(1-7) in serum and the expression of ACE2,Mas protein and mRNA in aorta decreased(P<0.05,P<0.01).Compared with the model group,the SBP of each intervention group decreased at each time after intervention and the expression of ACE2 mRNA in aorta increased(P<0.05,P<0.01).The levels of REN,ALD,Ang Ⅱ in serum and Ang Ⅱ expression in aorta of rats in irbesartan group decreased,while the levels of ACE2 and Ang(1-7) increased(P<0.05,P<0.01).In the high dose TXZT group,the levels of REN,ALD,Ang Ⅱ in serum and Ang Ⅱ expression in aorta decreased,while the levels of ACE2 and Ang(1-7)in serum,ACE2 expression in aorta and Mas mRNA increased(P<0.05,P<0.01).The

关 键 词：高血压 肾素-血管紧张素-醛固酮系统 血管紧张素转换酶2/血管紧张素(1-7)/Mas轴 

分 类 号：R285.5[医药卫生—中药学]