复方钩藤降压片对大鼠心肌CT-1/JAK-STAT通路蛋白表达的影响
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摘要
目的观察复方钩藤降压片对自发性高血压大鼠(SHR)心肌营养素-1(CT-1)/JAK-STAT通路蛋白表达影响,探讨其干预逆转高血压左室肥厚的机制。方法将50只SHR按随机数字表法分为5组,复方钩藤降压片高剂量组(H组,129. 6 mg/m L)、复方钩藤降压片中剂量组(M组,86. 4 mg/m L)、复方钩藤降压片低剂量组(L组,43. 2 mg/m L)、贝那普利组(B组,0. 9 mg/m L)、SHR模型对照组(S组),每组10只,另选取10只Wistar大鼠为正常对照组(W组),每天灌胃1次,持续干预24周后取材,采用免疫组化法检测心肌局部CT-1的含量,Western blot法检测心肌JAK1/STAT3蛋白表达水平。结果与W组比较,S组心肌组织中CT-1表达量和JAK1、STAT3蛋白表达水平均升高(P <0. 05)。与S组比较,B组、H组、M组及L组心肌组织中CT-1表达量降低(P <0. 05),JAK1、STAT3蛋白表达水平降低(P <0. 05)。各药物干预组间CT-1表达量差异无统计学意义(P> 0. 05),H组、M组、L组呈剂量依赖性JAK1、STAT3蛋白表达量递增,差异有统计学意义(P <0. 05)。与B组比较,H组、M组JAK1、STAT3蛋白表达水平均降低(P <0. 05)。结论复方钩藤降压片具有一定抑制SHR心肌CT-1/JAK-STAT通路蛋白表达的作用,可能通过降低心脏局部CT-1表达水平,抑制JAK-STAT通路,干预逆转左室肥厚。
Objective To explore the mechanism of reversing left ventricular hypertrophy in spontaneous hypertension rats( SHR) by the intervention of Compound Uncaria Antihypertensive Tablet from the point of view of interfering with the protein expression of cardiotrophin-1( CT-1)/JAK-STAT pathway in rats' cardiac myocardium. Methods Totally 50 SHR were divided into 5 groups,the high dose group( group H,129. 6 mg/m L),the middle dose group( group M,86. 4 mg/m L),the low dose group( group L,43. 2 mg/m L),the benazepril group( group B,0. 9 mg/m L),and the SHR model control group( group S) according to the random number table,10 in each group. 10 Wistar rats were recruited in a normal control group( group W),then perfomed gastric lavage once a day,and continued the intervention for 24 weeks. The contents of partial myocardial CT-1 and protein expression level of myocardial JAK1/STAT3 were detected by immunohistochemistry and Western blot respectively. Results Compared with group W,the expression level of CT-1 and the protein expression level of JAK1 and STAT3 in myocardial tissue were uniformly increased in group S(P < 0. 05). Compared with group S,expression levels of CT-1 in myocardial tissue decreased(P < 0. 05),while protein expression level of JAK1 and STAT3 decreased in group B,H,M and L(P < 0. 05). There was no statistically significant difference in the expression of CT-1 among the intervention groups(P > 0. 05). The protein expression levels of dose-dependent JAK1 and STAT3 increased in group H,M and L,and the difference was statistically significant(P < 0. 05). Compared with group B,the expression level of JAK1 and STAT3 decreased,the difference was statistically significant(P < 0. 05). Conclusion Compound Uncaria Antihypertensive Tablet had a certain inhibitory effect on the protein expression of CT-1/JAK-STAT pathway protein,and its possible mechanism to reverse left ventricular hypertrophy is to reduce expression level of cardiac partial CT-1 and inhibit the JAK-STAT pathway,and then give full scope to reverse the left ventricular hypertrophy.
Objective To explore the mechanism of reversing left ventricular hypertrophy in spontaneous hypertension rats( SHR) by the intervention of Compound Uncaria Antihypertensive Tablet from the point of view of interfering with the protein expression of cardiotrophin-1( CT-1)/JAK-STAT pathway in rats' cardiac myocardium. Methods Totally 50 SHR were divided into 5 groups,the high dose group( group H,129. 6 mg/m L),the middle dose group( group M,86. 4 mg/m L),the low dose group( group L,43. 2 mg/m L),the benazepril group( group B,0. 9 mg/m L),and the SHR model control group( group S) according to the random number table,10 in each group. 10 Wistar rats were recruited in a normal control group( group W),then perfomed gastric lavage once a day,and continued the intervention for 24 weeks. The contents of partial myocardial CT-1 and protein expression level of myocardial JAK1/STAT3 were detected by immunohistochemistry and Western blot respectively. Results Compared with group W,the expression level of CT-1 and the protein expression level of JAK1 and STAT3 in myocardial tissue were uniformly increased in group S(P < 0. 05). Compared with group S,expression levels of CT-1 in myocardial tissue decreased(P < 0. 05),while protein expression level of JAK1 and STAT3 decreased in group B,H,M and L(P < 0. 05). There was no statistically significant difference in the expression of CT-1 among the intervention groups(P > 0. 05). The protein expression levels of dose-dependent JAK1 and STAT3 increased in group H,M and L,and the difference was statistically significant(P < 0. 05). Compared with group B,the expression level of JAK1 and STAT3 decreased,the difference was statistically significant(P < 0. 05). Conclusion Compound Uncaria Antihypertensive Tablet had a certain inhibitory effect on the protein expression of CT-1/JAK-STAT pathway protein,and its possible mechanism to reverse left ventricular hypertrophy is to reduce expression level of cardiac partial CT-1 and inhibit the JAK-STAT pathway,and then give full scope to reverse the left ventricular hypertrophy.
引文
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[11]Lopez N,Dtez J,Fortuflo MA.Differential hypertrophic effects of cardiotmphin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats[J].J Mol Cell Cardiol,2006,41(5):902-913.
[12]González A,López B,Ravassa S,et al.Cardiotrophin-1 in hypertensive heart disease[J].Endocrine,2012,42(1):9-17.
[13]曾勇,谭超,叶舒婷,等.复方钩藤降压片对自发性高血压大鼠血压及炎症水平的影响[J].中华中医药学刊,2014,32(12):2983-85.
[14]曾勇,张稳,王顺民,等.复方钩藤降压片对自发性高血压大鼠血压与左室肥厚的影响[J].中华中医药学刊,2018,36(5):1106-1108.
[15]曾勇,谭超,文爱珍,等.复方钩藤降压片对SHR腹主动脉壁白细胞黏附浸润及E-选择素表达的影响[J].中华中医药学刊,2016,34(5):1105-1107.
[16]叶舒婷,谭超,黄娟娟,等.复方钩藤降压片治疗高血压病左室肥厚(阴虚阳亢、瘀血阻络证)31例临床观察[J].中医药导报,2013,19(5):8-10.
[2]Braz Nogueira.Regression of left ventricular hypertrophy in hypertension-does it reduce cardiovascular risk?[J].Rev Port Cardiol,2005,24(9):1007-1013.
[3]吴婷婷,屈会化,胡丽娜,等.基于树鼩体表面积的树鼩与人类及其它实验动物等效剂量换算系数的测算[J].中华中医药杂志,2015,30(1):203-205.
[4]Liu J,Shen O,Wu Y.Simvastatin prevents cardiac hypertrophy in vitro and in vivo via JAK/STATpathway[J].Life Sci,2008,82(19):991-996.
[5]Kanazawa H,Ieda M,Kimura K,et al.Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gpl30-signaling cytokines in rodents[J].J Clin Invest,2010,120(17):408-421.
[6]Pemberton CJ,Raudsepp SD,Yandle TG,et al.Plasma cardiotrophin-1 is elevated in human hypertension and stimulated by ventricular stretch[J].Cardiovase Res,2005,68(1):109-117.
[7]Schillaci G,Pucci G,Perlini S.From hypertension to hypertrophy to heart failure:the role of cardiotrophin-1[J].J Hypertens,2013,31(3):474-476.
[8]Fukuzana J,Booz GW,Hunt RA,et al.Cardioortphin-1increases angiotensinogen mRNA in rat cardiac myocytes through STAT3 an autocrine loop for hypertrophy[J].Hypertension,2000,35(6):1191-1196.
[9]CalabróP,Limongelli G,Riegler L,et al.Novel insights into the role of cardiotrophin-1 in cardiovascular diseases[J].J Mol Cell Cardiol,2009,46(2):142-148.
[10]Robador PA,Moreno MU,Beloqui O,et al.Protective effect of the 1742(C/G)polymorphism of human cardiotrophin-1 against left ventricular hypertrophy in essential hypertension[J].J Hypertens,2010,28(11):2219-2226.
[11]Lopez N,Dtez J,Fortuflo MA.Differential hypertrophic effects of cardiotmphin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats[J].J Mol Cell Cardiol,2006,41(5):902-913.
[12]González A,López B,Ravassa S,et al.Cardiotrophin-1 in hypertensive heart disease[J].Endocrine,2012,42(1):9-17.
[13]曾勇,谭超,叶舒婷,等.复方钩藤降压片对自发性高血压大鼠血压及炎症水平的影响[J].中华中医药学刊,2014,32(12):2983-85.
[14]曾勇,张稳,王顺民,等.复方钩藤降压片对自发性高血压大鼠血压与左室肥厚的影响[J].中华中医药学刊,2018,36(5):1106-1108.
[15]曾勇,谭超,文爱珍,等.复方钩藤降压片对SHR腹主动脉壁白细胞黏附浸润及E-选择素表达的影响[J].中华中医药学刊,2016,34(5):1105-1107.
[16]叶舒婷,谭超,黄娟娟,等.复方钩藤降压片治疗高血压病左室肥厚(阴虚阳亢、瘀血阻络证)31例临床观察[J].中医药导报,2013,19(5):8-10.