复方芪麻胶囊对SHR大鼠RAS系统ACE-AngⅡ-AT1轴与ACE2-Ang(1-7)-Mas轴动态平衡的调控作用研究
|
摘要
目的探索复方芪麻胶囊对自发性高血压大鼠(SHR)肾素-血管紧张素系统(RAS)的动态平衡调节作用。方法将大鼠按血压值分为正常组(WKY组),模型组(SHR组),卡托普利组(Captopril组),复方芪麻胶囊高(QM-H)、中(QM-M)、低(QM-L)剂量组,每组10只,连续灌胃给药4周。给药前、给药2周和给药4周测定各组大鼠血压。末次给药后,各大鼠麻醉后取血,分离血清,采用酶联免疫吸附试验(ELISA)试剂盒检测大鼠血清中血管紧张素转换酶(ACE)、血管紧张素(Ang)Ⅱ、血管紧张素1型受体(AT1)、ACE2、Ang(1-7)、Mas含量。结果在给药前,与WKY组相比,各组SHR高血压模型大鼠收缩压、舒张压均显著升高(P<0.01)。SHR组、Captopril组、QM-H、QM-M、QM-L组之间两两比较,收缩压、舒张压差异均无统计学意义(P>0.05);在给药2周后与4周后,与WKY组比较,SHR组大鼠收缩压、舒张压均明显升高(P<0.01);与SHR组大鼠比较,Captopril组、QMH、QM-M、QM-L组大鼠收缩压、舒张压均明显降低(P<0.01)。与WKY组比较,SHR组大鼠血清ACE、AngⅡ、AT1含量均显著上升(P<0.01);与SHR组大鼠比较,Captopril组、QM-H、QM-M、QM-L组ACE、AngⅡ、AT1含量均显著降低(P<0.05或P<0.01)。与WKY组比较,SHR组大鼠血清ACE2、Ang (1-7)、Mas含量均显著性降低(P<0.01);与SHR组大鼠比较,Captopril组、QM-H、QM-M、QM-L组ACE2、Ang(1-7)、Mas含量均显著升高(P<0.05或P<0.01)。结论复方芪麻胶囊可明显降低SHR大鼠的收缩压和舒张压,其作用可能与抑制ACE-AngⅡ-AT1轴,增强ACE2-Ang(1-7)-Mas轴有关。
Objective To explore the dynamic balance regulation effect of compound Qima capsule on RAS system in spontaneously hypertensive rats(SHR). Methods The rats were divided into sham group(WKY group),SHR group, captopril group, compound Qima capsule high dosage group, middle dosage group and low dosage group.Ten rats in each group were administered by continuous gavage for 4 weeks. The blood pressure of each group was measured before administration, 2 weeks after administration, and 4 weeks after administration. After the last admin-istration, ELISA kit was used to detect the contents of ACE, AngⅡ, AT1, ACE2, Ang(1-7) and Mas in the serum of rats. Results Before administration, compared with the WKY group, the systolic blood pressure and diastolic blood pressure of the SHR hypertensive rats were significantly increased(P<0.01). There were no significant differences in systolic blood pressure and diastolic blood pressure among SHR group, captopril group, QM-H, QM-M and QM-L groups(P>0.05); after 2 weeks and 4 weeks of administration, the systolic and diastolic blood pressures of the SHR group were significantly higher than those of the WKY group(P<0.01); compared with the SHR group, the systolic blood pressure and diastolic blood pressure of the captopril group, QM-H, QM-M and QM-L groups were significantly decreased(P<0.01). Compared with WKY group, serum ACE, AngII and AT1 levels in SHR group were significantly increased(P<0.01); compared with SHR group, ACE, AngⅡ and AT1 contents in captopril group, QM-H, QM-M, QML group were significantly decreased(P<0.05 or P<0.01). Compared with WKY group, serum ACE2, Ang(1-7) and Mas were significantly decreased in SHR group(P<0.01); Compared with SHR group, the levels of ACE2, Ang(1-7) and Mas in the captopril group, QM-H, QM-M and QM-L group were significantly increased(P<0.05 or P<0.01). Conclusion Compound Qima capsule can significantly reduce systolic and diastolic blood pressure in SHR rats, which may be related to inhibition of ACE-AngⅡ-AT1 axis and enhancement of ACE2-Ang(1-7)-Mas axis.
Objective To explore the dynamic balance regulation effect of compound Qima capsule on RAS system in spontaneously hypertensive rats(SHR). Methods The rats were divided into sham group(WKY group),SHR group, captopril group, compound Qima capsule high dosage group, middle dosage group and low dosage group.Ten rats in each group were administered by continuous gavage for 4 weeks. The blood pressure of each group was measured before administration, 2 weeks after administration, and 4 weeks after administration. After the last admin-istration, ELISA kit was used to detect the contents of ACE, AngⅡ, AT1, ACE2, Ang(1-7) and Mas in the serum of rats. Results Before administration, compared with the WKY group, the systolic blood pressure and diastolic blood pressure of the SHR hypertensive rats were significantly increased(P<0.01). There were no significant differences in systolic blood pressure and diastolic blood pressure among SHR group, captopril group, QM-H, QM-M and QM-L groups(P>0.05); after 2 weeks and 4 weeks of administration, the systolic and diastolic blood pressures of the SHR group were significantly higher than those of the WKY group(P<0.01); compared with the SHR group, the systolic blood pressure and diastolic blood pressure of the captopril group, QM-H, QM-M and QM-L groups were significantly decreased(P<0.01). Compared with WKY group, serum ACE, AngII and AT1 levels in SHR group were significantly increased(P<0.01); compared with SHR group, ACE, AngⅡ and AT1 contents in captopril group, QM-H, QM-M, QML group were significantly decreased(P<0.05 or P<0.01). Compared with WKY group, serum ACE2, Ang(1-7) and Mas were significantly decreased in SHR group(P<0.01); Compared with SHR group, the levels of ACE2, Ang(1-7) and Mas in the captopril group, QM-H, QM-M and QM-L group were significantly increased(P<0.05 or P<0.01). Conclusion Compound Qima capsule can significantly reduce systolic and diastolic blood pressure in SHR rats, which may be related to inhibition of ACE-AngⅡ-AT1 axis and enhancement of ACE2-Ang(1-7)-Mas axis.
引文
[1]李艳,孙胜利.老年脑卒中合并高血压与其关联危险因素的相互作用关系[J].山西医药杂志,2018,47(9):1032-1036.
[2]黄培红,靳利利,李典鸿,等.复方芪麻胶囊对气虚痰浊型单纯收缩期高血压患者血压及炎症因子的影响[J].河南中医,2011,31(6):618-620.
[3]黄琳,王清海,李典鸿,等.复方芪麻胶囊对气虚痰浊型高血压患者动态血压的影响[J].中国实验方剂学杂志,2004,13(5):57-58.
[4]靳利利,丁达,郭英普,等.复方芪麻胶囊治疗气虚痰浊型单纯收缩期高血压病60例临床观察[J].广州中医药大学学报,2010,27(3):217-221.
[5]甘海宁,赵靖宇,黄琳,等.复方芪麻胶囊对肾性高血压大鼠血压及肾素-血管紧张素-醛固酮系统的影响[J].中华中医药学刊,2016,34(7):1746-1748.
[6]黄丹娥,黄琳,赵靖宇,等.复方芪麻胶囊对自发性高血压大鼠血压及血清NO、ET、AngⅡ的影响[J].广东药学院学报,2015,31(6):791-794.
[7]吴永刚,陈磊,蒋守涛,等.复方芪麻胶囊含药血清对血管紧张素Ⅱ诱导损伤脐静脉内皮细胞相关因子的影响[J].河南中医,2018,38(4):548-551.
[8]Unger T.The role of the renin-angiotensin system in the development of cardiovascular disease[J].Am J Cardiol,2002,89(2A):3A-10A.
[9]周华,张翠芳,陈瑞瑞,等.RNA干扰下调血管紧张素转换酶和血管紧张素Ⅱ1型受体对自发性高血压大鼠血压及肾脏损伤的影响[J].中国药物与临床,2017,17(12):1754-1758.
[10]Vickers C,Hales P,Kaushik V,et al.Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase[J].J Biol Chem,2002,277(17):14838-14843.
[11]Ferreira AJ,Santos RA.Cardiovascular actions of angiotensin-(1-7)[J].Braz J Med Biol Res,2005,38(4):499-507.
[12]Murugan D,Lau Y,Lau C,et al.Angiotensin 1-7 protects against angiotensinⅡ-induced endoplasmic reticulum stress and endothelial dysfunction via mas receptor[J].PLoS ONE,2015,10(12):e145413.
[13]Liang B,Wang X,Zhang N,et al.Angiotensin-(1-7)attenuates angiotensinⅡ-induced ICAM-1,VCAM-1,and MCP-1 expression via the MAS receptor through suppression of P38 and NF-kappa B pathways in HUVECs[J].Cell Physiol Biochem,2015,35(6):2472-2482.
[14]Wu ZT,Ren CZ,Yang YH,et al.The PI3K signaling-mediated nitric oxide contributes to cardiovascular effects of angiotensin-(1-7)in the nucleus tractus solitarii of rats[J].Nitric Oxide,2016,52:56-65.
[2]黄培红,靳利利,李典鸿,等.复方芪麻胶囊对气虚痰浊型单纯收缩期高血压患者血压及炎症因子的影响[J].河南中医,2011,31(6):618-620.
[3]黄琳,王清海,李典鸿,等.复方芪麻胶囊对气虚痰浊型高血压患者动态血压的影响[J].中国实验方剂学杂志,2004,13(5):57-58.
[4]靳利利,丁达,郭英普,等.复方芪麻胶囊治疗气虚痰浊型单纯收缩期高血压病60例临床观察[J].广州中医药大学学报,2010,27(3):217-221.
[5]甘海宁,赵靖宇,黄琳,等.复方芪麻胶囊对肾性高血压大鼠血压及肾素-血管紧张素-醛固酮系统的影响[J].中华中医药学刊,2016,34(7):1746-1748.
[6]黄丹娥,黄琳,赵靖宇,等.复方芪麻胶囊对自发性高血压大鼠血压及血清NO、ET、AngⅡ的影响[J].广东药学院学报,2015,31(6):791-794.
[7]吴永刚,陈磊,蒋守涛,等.复方芪麻胶囊含药血清对血管紧张素Ⅱ诱导损伤脐静脉内皮细胞相关因子的影响[J].河南中医,2018,38(4):548-551.
[8]Unger T.The role of the renin-angiotensin system in the development of cardiovascular disease[J].Am J Cardiol,2002,89(2A):3A-10A.
[9]周华,张翠芳,陈瑞瑞,等.RNA干扰下调血管紧张素转换酶和血管紧张素Ⅱ1型受体对自发性高血压大鼠血压及肾脏损伤的影响[J].中国药物与临床,2017,17(12):1754-1758.
[10]Vickers C,Hales P,Kaushik V,et al.Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase[J].J Biol Chem,2002,277(17):14838-14843.
[11]Ferreira AJ,Santos RA.Cardiovascular actions of angiotensin-(1-7)[J].Braz J Med Biol Res,2005,38(4):499-507.
[12]Murugan D,Lau Y,Lau C,et al.Angiotensin 1-7 protects against angiotensinⅡ-induced endoplasmic reticulum stress and endothelial dysfunction via mas receptor[J].PLoS ONE,2015,10(12):e145413.
[13]Liang B,Wang X,Zhang N,et al.Angiotensin-(1-7)attenuates angiotensinⅡ-induced ICAM-1,VCAM-1,and MCP-1 expression via the MAS receptor through suppression of P38 and NF-kappa B pathways in HUVECs[J].Cell Physiol Biochem,2015,35(6):2472-2482.
[14]Wu ZT,Ren CZ,Yang YH,et al.The PI3K signaling-mediated nitric oxide contributes to cardiovascular effects of angiotensin-(1-7)in the nucleus tractus solitarii of rats[J].Nitric Oxide,2016,52:56-65.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |