基于TGF-β/Smads信号通路探究养心通脉方调控慢性心力衰竭血瘀证大鼠的作用机制  

Exploring the mechanism of action for Yangxin Tongmai Formula in regulating rats with chronic heart failure of blood stasis pattern based on TGF-β/Smads signaling pathway

作　　者：肖清玄 郭志华[1] 罗佳敏 陈宇霞 张书萌 于子璇 陈伶利[1] 李杰[1] XIAO Qingxuan;GUO Zhihua;LUO Jiamin;CHEN Yuxia;ZHANG Shumeng;YU Zixuan;CHEN Lingli;LI Jie(Hunan University of Chinese Medicine,Changsha,Hunan 410208,China)

机构地区：[1]湖南中医药大学,湖南长沙410208

出　　处：《湖南中医药大学学报》2023年第8期1353-1360,共8页Journal of Hunan University of Chinese Medicine

基　　金：国家自然科学基金项目(81874375);湖南省自然科学基金项目(2020JJ4464);湖南省中医药科研计划重点项目(2021024);湖南中医药大学研究生创新课题(2022CX57)。

摘　　要：目的基于转化生长因子-β(tansforming growth factor-β,TGF-β)/Smads信号通路探讨养心通脉方对慢性心力衰竭(chronic heart failure,CHF)血瘀证大鼠心肌纤维化和炎症损伤的影响。方法通过随机数字表法将45只SD雄性大鼠分为造模组(27只)、正常组(12只)和假手术组(6只),适应性喂养1周后行冠脉结扎术造模,术后10 min行心电图检测,6周后检测超声心动图、血清N端前脑钠肽(N-terminal pro-brain natriuretic peptide,NT-pro BNP)含量和血液流变学相关指标。成模后,运用随机数字表法从造模组中取18只大鼠均分为中药组、西医组和模型组,中药组予养心通脉方溶液12 g/kg灌胃,西药组予以缬沙坦溶液0.8 g/kg灌胃,正常组、假手术组和模型组予等量蒸馏水,每日1次,持续4周。药物干预结束后,超声心动图检测心功能指标,HE染色和Masson染色观察大鼠心肌组织病理改变及纤维化程度,ELISA法检测大鼠血清NT-pro BNP和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-10(interleukin-10,IL-10)含量,Western blot法检测大鼠心肌组织TGF-β/Smads信号通路相关蛋白表达。结果与正常组比较,造模组大鼠心电图出现明显的ST段上抬,大鼠血清NT-pro BNP含量显著升高(P<0.01),左室射血分数(left ventricular ejection fraction,LVEF)水平显著下降(P<0.01),全血高切黏度、中切黏度、低切黏度显著升高(P<0.01)。药物干预4周后,与正常组比较,模型组LVEF明显降低(P<0.01),血清NT-Pro BNP、TNF-α、IL-1β及IL-6水平上升(P<0.01),IL-10水平明显下降(P<0.01),心肌组织ANGPT2、TGF-β1、Smad 2、Smad 3蛋白表达明显升高(P<0.01);与模型组比较,中药组、西药组LVEF水平上升(P<0.01),血清NT-pro BNP和TNF-α、IL-1β、IL-6水平降低(P<0.01),IL-10含量增多(P<0.01),心肌组织TGF-β1、Smad2、Smad3蛋白表达减少(P<0.05或P<0.01)。结论冠脉结Objective To observe the effects of Yangxin Tongmai Formula(YXTMF)on myocardial fibrosis and inflammatory injury in rats with chronic heart failure(CHF)of blood stasis pattern based on the transforming growth factor-β(TGF-β)/Smads signaling pathway.Methods A total of 45 male SD rats were divided into modeling group(n=27),normal group(n=12)and sham group(n=6)by random number table method.Coronary ligation modeling was performed after 1 week of adaptive feeding.Electrocardiography was performed 10 mins after surgery.Echocardiography,serum N-terminal pro-brain natriuretic peptide(NT-pro BNP)content,and hemorheological indicators were checked 6 weeks later.After modeling,18 rats taken from the modeling group by random number table method were randomly subdivided into Chinese medicine group(with YXTMF solution gavage,12 g/kg),western medicine group(with valsartan solution gavage,0.8 g/kg)and model group.The normal group,sham group,and model group were given equal amount of distilled water.All groups had been provided with corresponding drugs or distilled water once daily for 4 weeks.After 4 weeks of drug intervention,echocardiography was used to examine the cardiac function indicators;HE staining and Masson staining were used to observe the pathological changes and fibrosis degree of rat myocardial tissue;ELISA method was used to test the levels of serum NT-pro BNP,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-10(IL-10)in rats;Western blot method was used to check the TGF-β/Smads signaling pathway-related protein expressions in rat myocardial tissue.Results Compared with normal group,rats in model group showed significant ST-segment elevation in electrocardiogram,significantly increased serum NT-pro BNP content(P<0.01),significantly decreased left ventricular ejection fraction(LVEF)level(P<0.01),and significantly increased whole blood viscosity at high,medium,and low shear rate(P<0.01).After 4 weeks of drug intervention,compared with normal group,the rats in model grou

关 键 词：TGF-β/Smads信号通路 慢性心力衰竭 血瘀证 养心通脉方 炎症损伤 心肌纤维化 

分 类 号：R285.5[医药卫生—中药学]