[1]惠嫣然,董 菲,贾文浩,等.基于TGF-β1/Smad2/3信号通路研究芪参六味方对自发性高血压大鼠心肌纤维化的影响[J].陕西中医,2023,(10):1337-1343.[doi:DOI:10.3969/j.issn.1000-7369.2023.10.002]
　HUI Yanran,DONG Fei,JIA Wenhao,et al.Mechanism of Qishen Liuwei formula on myocardial fibrosis in SHR through TGF-β1/Smad2/3 pathway[J].,2023,(10):1337-1343.[doi:DOI:10.3969/j.issn.1000-7369.2023.10.002]
点击复制

基于TGF-β1/Smad2/3信号通路研究芪参六味方对自发性高血压大鼠心肌纤维化的影响
分享到：

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2023年10期
页码:
1337-1343
栏目:
基础研究
出版日期:
2023-10-05

文章信息/Info

Title:
Mechanism of Qishen Liuwei formula on myocardial fibrosis in SHR through TGF-β1/Smad2/3 pathway
作者:
惠嫣然1; 董 菲2; 贾文浩3; 肖华丽4; 余林波1; 黄丽君1; 毛天诗1; 林 谦5; 周 鹍6
(1.北京中医药大学,北京 100029; 2.北京市宣武中医医院,北京 100050; 3.北京中医药大学第三附属医院,北京 100029; 4.浙江大学医学院附属邵逸夫医院新疆兵团阿拉尔医院,新疆 阿拉尔 843300; 5.北京中医药大学东直门医院,北京 100700; 6.北京中医药大学东方医院,北京 100078)
Author(s):
HUI Yanran; DONG Fei; JIA Wenhao; XIAO Huali; YU Linbo; HUANG Lijun; MAO Tianshi; LIN Qian; ZHOU Kun
(Beijing University of Chinese Medicine,Beijing 100029,China)
关键词:
自发性高血压;  芪参六味方;  心肌纤维化;  TGF-β1/Smad2/3信号通路;  大鼠
Keywords:
Spontaneous hypertensive;  Qishen Liuwei formula;  Myocardial fibrosis;  TGF-β1/Smad2/3 pathway;  Rats
分类号:
R 544.1
DOI:
DOI:10.3969/j.issn.1000-7369.2023.10.002
文献标志码:
A
摘要:
目的:采用芪参六味方干预自发性高血压大鼠(SHR)心肌纤维化(MF)模型,观察其对大鼠MF的影响并探讨其作用机制。方法:SHR大鼠15只,分为模型组、中药组和氯沙坦钾组,每组5只。另魏-凯二氏大鼠(WKY)5只作为对照组。干预12周后检测各组大鼠超声心动图,处死后取左室心肌组织进行相关检测。采用Masson染色及苦味酸-天狼猩红染色,观察心肌组织胶原含量与分布; 采用Western blot法测定各组大鼠心肌组织中Ⅰ型胶原(Collagen Ⅰ)、Ⅲ型胶原(Collagen Ⅲ)、基质金属蛋白酶(MMP)-9、基质金属蛋白酶抑制剂(TIMP)-1、转化生长因子(TGF)-β1、Smad2、Smad3蛋白的表达; 采用RT-PCR法检测TGF-β1、Smad2、Smad3 mRNA的表达。结果:干预12周后,与模型组比较,中药组镜下胶原纤维明显减少,排列较均匀,E/E'、心肌组织胶原纤维面积百分比、Collagen Ⅰ/Collagen Ⅲ明显降低(P<0.05),Collagen Ⅰ、Collagen Ⅲ、MMP-9、TGF-β1、Smad2、Smad3蛋白表达量均降低(P<0.05),TGF-β1、Smad2 mRNA表达量下降(P<0.05)。结论:芪参六味方可通过调控TGF-β1/Smad2/3信号通路,减轻细胞外基质的沉积,改善SHR大鼠心肌纤维化。
Abstract:
Objective:To investigate the effect and mechanism of Qishen Liuwei formula on myocardial fibrosis in spontaneously hypertensive rats.Methods:SHR were divided into model group, Qishen Liuwei formula group,and losartan potassium group,with 5 rats in each group.5 WYK were selected as the control group.After 12 weeks of intervention,the echocardiography was detected,and then the rats were killed,and myocardial tissue were taken for relevant testing.Masson staining and picric acid-sirius scarlet staining were used to observe the content and distribution of myocardial collagen.The Western blot method was used to determine the expression of Collagen Ⅰ,Collagen Ⅲ,MMP-9,TIMP-1,TGF-β1,Smad2 and Smad3 proteins in the myocardial tissues of rats.RT-PCR was used to detect the expression of TGF-β1,Smad2 and Smad3 mRNA.Results:After 12 weeks of intervention,compared with the model group,the microscopic collagen fibers in the Qishen Liuwei formula group were reduced and the arrangement was more uniform,E/E',the percentage of collagen fiber area of myocardial tissue and Collagen Ⅰ/Collagen Ⅲ were reduced(P<0.05),and the expression of Collagen Ⅰ,Collagen Ⅲ,MMP-9,TGF-β1,Smad2 and Smad3 proteins were decreased(P<0.05),TGF-β1,Smad2 mRNA expression levels were reduced(P<0.05).Conclusion:Qishen Liuwei formula can reduce the deposition of extracellular matrix and improve the myocardial fibrosis in SHR rats by regulating the TGF-β1/Smad2/3 pathway.

参考文献/References:

[1] 张 梅,吴 静,张 笑,等.2018年中国成年居民高血压患病与控制状况研究[J].中华流行病学杂志,2021,42(10):1780-1789.
[2] 易胜利,邓 玮.心肌纤维化发病机制研究进展[J].现代医药卫生,2022,38(12):2051-2055.
[3] Istratoaie O,Pirici I,Ofiteru AM,et al.Evaluation of cardiac microvasculature in patients with diffuse myocardial fibrosis[J].Embryol,2016,57(4):1351-1356.
[4] 张 妍,周纳纳,韩 茹,等.益心附葶饮对主动脉缩窄大鼠心肌纤维化及p38MAPK/NF-κB p65信号通路的影响[J].陕西中医,2022,43(3):287-291.
[5] An Z,Yang G,Zheng HK,et al.Biomarkers in patients with myocardial fibrosis[J].Open Life Sciences,2017,12(1):337-344.
[6] Foronjy RF,Sun J,Armiento J.Transgenic expression of matrix metalloproteinase-1 inhibits myocardial fibrosis and prevents the transition to heart failure in a pressure overload mouse model[J].Hypertens Res,2008,31:725-735.
[7] Ogawa K,Chen FF,Kuang CZ,et al.Suppression of matrix metalloproteinase-9 transcription by transforming growth factor-β is mediated by a nuclear factor-κB site[J].Biochemical Journal,2004,381(2):413-422.
[8] Gao Q,Cui XY,Dong F,et al.Efficacy and safety of bushenjiangya-optimized granule granule for left ventricular diastolic dysfunction in hypertensive patients:A double-blind,randomized,placebo-controlled trial[J].Evid Based Complement Alternat Med,2020,18:7190352.
[9] 崔晓云,范文英,李品慧,等.益气活血补肾降压方治疗高血压左室舒张功能障碍的临床研究[J].中华中医药杂志,2018,33(3):1152-1155.
[10] 周 鹍,范文英,孟 妍,等.益气活血法治疗高血压伴无症状舒张功能不全的临床研究[J].中西医结合心脑血管病杂志,2017,15(22):2811-2812.
[11] 范金茹,王行宽,熊国强.高血压左室肥厚中医病名、病位、病因病机探讨[J].中医药通报,2005,4(2):19-21.
[12] 周明龙,姚祖培.活血化瘀方药防治高血压心肌纤维化研究进展[J].中西医结合心脑血管病杂志,2013,11(2):209-211.
[13] 吴美芳,吕仕超,张军平.心肌纤维化中医诊疗思路探析[J].时珍国医国药,2015,26(3):677-679.
[14] 王奇林,董昌武,徐 慧,等.滋阴潜阳方对自发性高血压大鼠心肌纤维化相关蛋白表达的影响[J].安徽中医药大学学报,2023,42(3):83-87.
[15] 蒋嘉烨,王现珍,罗珊珊,等.半夏白术天麻汤对自发性高血压大鼠左心室肥厚的影响[J].中国中西医结合杂志,2010,21(10):1061-1066.
[16] 崔晓云,谭 弘,张学江,等.益气活血-高血压舒张功能障碍的中医药防治新思路[J].中国中医基础医学杂志,2015,21(2):181-182.
[17] 刘 静,徐江林,石晓路,等.益气活血法对舒张性心力衰竭大鼠心肌细胞钙稳态的影响[J].北京中医药大学学报,2022,45(2):165-175.
[18] 孙娅楠,农一兵,崔晓云,等.黄芪对乳鼠肥大心肌细胞钙瞬变及钙调蛋白激酶Ⅱ的影响[J].中国中医基础医学杂志,2013,19(1):44-46.
[19] 刘 静.基于心肌细胞钙稳态研究益气活血药对舒张性心功能不全的干预机制[D].北京:北京中医药大学,2017.
[20] 付亚梦,刘 昕.左房时相功能诊断冠状动脉粥样硬化性心脏病患者左室舒张功能障碍的价值[J].临床超声医学杂志,2023,25(1):39-43.
[21] 中华医学会超声医学分会超声心动图学组,中国医师协会心血管分会超声心动图专业委员会.超声心动图评估心脏收缩和舒张功能临床应用指南[J].中华超声影像学杂志,2020,29(6):461-477.
[22] Mark S,Ben C,Stuart AC.Targeting cardiac fibrosis in heart failure with preserved ejection fraction:Mirage or miracle?[J].EMBO Mol Med,2020,12:10865.
[23] 丁秀婷,刘 璠,刘建一,等.银杏内酯B对自发性高血压大鼠心肌纤维化及左心室肥厚的影响研究[J].陕西医学杂志,2017,46(7):823-825.
[24] 朱力权.益气活血补肾法治疗高血压左室舒张功能障碍的临床效果[J].内蒙古中医药,2021,40(7):13-14.
[25] 宋晓龙,宋 俊,潘仁友,等.利心水方治疗冠心病心力衰竭疗效及对患者心肌纤维化、心肌重构的影响[J].陕西中医,2022,43(2):197-200.
[26] Weber KT,Janicki JS,Shroff SG,et al.Collagen remodeling of the pressure-overloaded hypertrophied nonhuman primate myocardium[J].Circ Res,1988,62:757-765.
[27] Caulfield JB,Janicki JS.Structure and function of myocardial fibrillar collagen[J].Technol Health Care,1997,5:95-113.
[28] Chiao YA,Ramirez TA,Zamilpa R,et al.Matrix metalloproteinase-9 deletion attenuates myocardial fibrosis and diastolic dysfunction in ageing mice[J].Cardiovascular Research,2012,96(3):444-455.
[29] Munch J,Avanesov M,Bannas P,et al.Serum matrix metalloproteinases as quantitative biomarkers for myocardial fibrosis and sudden cardiac death risk stratification in patients with hypertrophic cardiomyopathy[J].Card Fail,2016,22:845-850.
[30] Benjamin EJ,Muntner P,Alonso A,et al.Heart disease and stroke statistics-2019 update:A report from the American Heart Association[J].Circulation,2019,139(10):562-528.
[31] Dziaio E,Tkacz K,Biszczuk P.Crosstalk between the TGF-β and WNT signalling pathways during cardiac fibrogenesis[J].Acta Biochim Pol,2018,65:341-349.
[32] Zhao M,Zheng S,Yang J,et al.Suppression of TGF-beta1/Smad signaling pathway by sesamin contributes to the attenuation of myocardial fibrosis in spontaneously hypertensive rats[J].PLoS One,2015,10(3):121312.
[33] Zhang Y,Shao L,Ma A,et al.Telmisartan delays myocardial fibrosis in rats with hypertensive left ventricular hypertrophy by TGF-beta1/Smad signal pathway[J].Hypertens Res,2014,37(1):43-49.
[34] 张 丽,彭 静,金 璟,等.妊娠期高血压疾病孕妇血清和胎盘组织中血管内皮生长因子、糖基化终末产物、转化生长因子-β1表达及其与病情严重程度相关性研究[J].陕西医学杂志,2022,51(8):953-956,960.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助面上项目(81874385)
更新日期/Last Update: 2023-10-09