针刺对自发性高血压大鼠血管紧张素Ⅱ及其受体1以及γ-氨基丁酸的影响
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摘要
目的观察针刺人迎、曲池、足三里穴对自发性高血压大鼠(SHR)的降压作用及对血清、肾、延髓血管紧张素Ⅱ(AngⅡ)、血管紧张素受体1(AT1R)的影响,以及针刺引起的交感调节中枢延髓头端腹外侧(RVLM)区γ-氨基丁酸(GABA)的变化。方法将30只自发性高血压大鼠(SHR)随机分为针刺组和SHR组,每组15只;另以15只WKY大鼠作为空白对照组。针刺组予针刺人迎、曲池、足三里穴20 min,每周刺6 d,休息1 d,疗程8周;SHR组和WKY组除不针刺干预外,抓取固定同针刺组。针刺干预结束2 d后测量血压,取材备测。结果针刺人迎、曲池、足三里穴可下调SHR血压,降低肾、延髓左侧RVLM区AngⅡ水平(P <0.05),但对血清AngⅡ无影响(P> 0.05)。免疫组化显示针刺组肾、延髓右侧RVLM区AT1R的表达降低,右侧RVLM区GABA表达升高(P <0.05)。结论针刺可通过下调AngⅡ水平及AT1R表达,升高GABA表达,从而抑制RAS活性及交感兴奋发挥降压效应,并可部分逆转肾损害。
Objective: To investigate the antihypertensive effect of acupuncture at Renying(ST9),Quchi(LI11)and Zusanli(ST36) points on spontaneously hypertensive rats(SHR),and to observe the effects of acupuncture on serum,kidney and medulla oblongata angiotensin Ⅱ(AngⅡ),angiotensin receptor 1(AT 1 R),and to observe the changes of gamma-aminobutyric acid(GABA) in the rostral ventrolateral medulla(RVLM) of the sympathetic regulatory center induced by acupuncture. Methods: Twenty spontaneously hypertensive rats(SHR) were randomly divided into acupuncture group and model group with 10 rats in each group and 10 WKY rats as blank group.Acupuncture group was given acupuncture at Renying(ST9),Quchi(LI11) and Zusanli(ST36) for 30 minutes,5 days a week,2 days off,8 weeks treatment course;model group and blank group,except for no acupuncture intervention,grasp and fix the same acupuncture group. After 2 days of acupuncture intervention,blood pressure was measured. Results: Acupuncture at Renying(ST9),Quchi(LI11) and Zusanli(ST36) could lower the blood pressure of SHR and the level of Ang Ⅱ in kidney and medulla oblongata,but had no effect on serum Ang Ⅱ. Immunohistochemistry showed that the expression of AT1 R in kidney and medulla oblongata decreased,while the expression of GABA increased in RVLM region. Conclusion: Acupuncture can decrease the level of AngⅡ and the expression of AT1 R,increase the expression of GABA,inhibit RAS activity and sympathetic excitation to play a hypotensive effect,and partly reverse renal damage.
Objective: To investigate the antihypertensive effect of acupuncture at Renying(ST9),Quchi(LI11)and Zusanli(ST36) points on spontaneously hypertensive rats(SHR),and to observe the effects of acupuncture on serum,kidney and medulla oblongata angiotensin Ⅱ(AngⅡ),angiotensin receptor 1(AT 1 R),and to observe the changes of gamma-aminobutyric acid(GABA) in the rostral ventrolateral medulla(RVLM) of the sympathetic regulatory center induced by acupuncture. Methods: Twenty spontaneously hypertensive rats(SHR) were randomly divided into acupuncture group and model group with 10 rats in each group and 10 WKY rats as blank group.Acupuncture group was given acupuncture at Renying(ST9),Quchi(LI11) and Zusanli(ST36) for 30 minutes,5 days a week,2 days off,8 weeks treatment course;model group and blank group,except for no acupuncture intervention,grasp and fix the same acupuncture group. After 2 days of acupuncture intervention,blood pressure was measured. Results: Acupuncture at Renying(ST9),Quchi(LI11) and Zusanli(ST36) could lower the blood pressure of SHR and the level of Ang Ⅱ in kidney and medulla oblongata,but had no effect on serum Ang Ⅱ. Immunohistochemistry showed that the expression of AT1 R in kidney and medulla oblongata decreased,while the expression of GABA increased in RVLM region. Conclusion: Acupuncture can decrease the level of AngⅡ and the expression of AT1 R,increase the expression of GABA,inhibit RAS activity and sympathetic excitation to play a hypotensive effect,and partly reverse renal damage.
引文
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[17]张文华.GABA_B受体通过Gi/o蛋白不同亚基调节下游信号及功能研究[D].武汉:华中科技大学,2014.
[18]沈智洁.RDN对高血压犬延髓头端腹外侧区Glu/GABA的影响及机制[D].长沙:中南大学,2014.
[19]吴照堂.孤束核中血管紧张素1-7通过Mas受体/PI3K/Akt通路上调一氧化氮释放[D].上海:第二军医大学,2013.
[20]张承荣.延髓Apelin/APJ系统参与应激性高血压大鼠发病并介导针刺降压[D].上海:复旦大学,2011.
[21]李宇清.针刺不同穴位对胃运动功能的影响[D].北京:中国中医科学院,2003.
[22]吴敬.急性脑卒中引发心肌酶谱变化及针刺干预效果[J].中国临床康复,2006,10(7):1-3.
[23]安娜,郭妍,芦娟,等.针刺“人迎”穴对自发性高血压大鼠下丘脑基因表达的影响[J].中医杂志2018,59(6):518-522.
[2]DiBona GF,Esler M.Translational medicine:the antihypertensive effect of renal denervation[J].Am J Physiol Regul Integr Comp Physiol,2010,298(2):R245-253.
[3]赵谭.血管紧张素原及胰岛素生长因子-1在糖尿病肾病进展中作用的研究[D].济南:济南大学,2013.
[4]刘必成.CTGF在介导肾脏肥大中的作用---体内外实验研究[D].南京:南京医科大学,2004.
[5]van den Meiracker AH,Boomsma F.The angiotensinⅡ-sympathetic nervous system connection[J].Journal of Hypertension,2003,21(8):1453-1454.
[6]Milner TA,Pickel VM.Receptor targeting in medullary nucle mediating baroreceptor reflexes[J].Cell Mol Neurobiol,2003,23(4-5):751-760.
[7]Heesch CM,Laiprasert JD,Kvochina L.RVLM glycine receptors mediate GABAA and GABAB independent sympathoinhibition from CVLM in rats[J].Brain Res,2006,1125(1):46-59.
[8]郝日雯,关伟,郭继龙,等.电针对二肾一夹高血压大鼠血压、血管重构的影响研究[J].山西中医学院学报,2017,19(4):16-19.
[9]Paxinos G,Watson C.The rat brain in stereotaxic coordinates[S].Academic Press,Sydney,1998.
[10]龙海波,牛红心,李小云,等.肾康丸对早期糖尿病肾病大鼠肾脏AngⅡ及其受体AT_1R表达的影响[J].南方医科大学学报,2010,30(4):805-809.
[11]Gonzalez AA,Luffman C,Bourgeois CR,et al.Angiotensin II-independent upregulation of cyclooxygenase-2 by activation of the(Pro)renin receptor in rat renal inner medullary cells[J].Hypertension,2013,61(2):443-449.
[12]Lochard N,Thibault G,Silversides DW,et al.Chronic production of angiotensin IV in the brain leads to hypertension that is reversible with an angiotensinⅡAT1 receptor antagonist[J].Circ Res,2004,94(11):1451-1457.
[13]田硕,杜冠华.肾素-血管紧张素系统的新成员:肾素原及其受体[J].中国新药杂志,2009,18(20):1942-1945.
[14]尹桂东,崔桂玉,邴艳华,等.下丘脑室旁核的Ⅰ组促代谢型谷氨酸受体在压力感受性反射调节中的作用[J].中国现代医学杂志,2010,20(10):1477-1481.
[15]Takano K,Yatabe MS,Abe A,et al.Characteristic expressions of GABA receptors and GABA producing/transporting molecules in rat kidney[J].PLoS One,2014,9(9):e105835.
[16]Ma P,Li T,Ji F,et al.Effect of GABA on blood pressure and blood dynamics of anesthetic rats[J].Int J Clin Exp Med,2015,8(8):14296-14302.
[17]张文华.GABA_B受体通过Gi/o蛋白不同亚基调节下游信号及功能研究[D].武汉:华中科技大学,2014.
[18]沈智洁.RDN对高血压犬延髓头端腹外侧区Glu/GABA的影响及机制[D].长沙:中南大学,2014.
[19]吴照堂.孤束核中血管紧张素1-7通过Mas受体/PI3K/Akt通路上调一氧化氮释放[D].上海:第二军医大学,2013.
[20]张承荣.延髓Apelin/APJ系统参与应激性高血压大鼠发病并介导针刺降压[D].上海:复旦大学,2011.
[21]李宇清.针刺不同穴位对胃运动功能的影响[D].北京:中国中医科学院,2003.
[22]吴敬.急性脑卒中引发心肌酶谱变化及针刺干预效果[J].中国临床康复,2006,10(7):1-3.
[23]安娜,郭妍,芦娟,等.针刺“人迎”穴对自发性高血压大鼠下丘脑基因表达的影响[J].中医杂志2018,59(6):518-522.