健心颗粒对气虚血瘀型心力衰竭大鼠心肌重构及CaN/NFATc3通路的影响  

Effects of Jianxin Granule on Myocardial Remodeling and CaN/NFATc3 Pathway in Rats with Heart Failure of Qi Deficiency and Blood Stasis

作　　者：陈成[1,2] 钟智慧 吴颖 胡毅 汤睿之 CHEN Cheng;ZHONG Zhi-hui;WU Ying;HU Yi;TANG Rui-zhi(Department of Geriatric Medicine,the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine,Fuzhou,350003;Key Laboratory of Integrative Medicine of Fujian Province University(Fujian University of Traditional Chinese Medicine),Fuzhou,350122)

机构地区：[1]福建中医药大学附属第二人民医院老年科,福州350003 [2]中西医结合基础福建省高校重点实验室(福建中医药大学),福州350122

出　　处：《中国中西医结合杂志》2024年第7期821-829,共9页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：福建省自然科学基金面上项目(No.2022J01343);中西医结合基础福建省高校重点实验室开放课题暨陈可冀中西医结合发展基金(No.KLIM2022001/CKJ2022001);福建中医药大学2022年度校管临床专项课题(No.XB2022028)。

摘　　要：目的 观察健心颗粒对气虚血瘀型心力衰竭(心衰)大鼠心肌重构的影响,并探讨其对钙调磷酸酶(Ca N)/活化T细胞核因子c3(NFATc3)通路的影响。方法 将24只雄性SD大鼠随机分为假手术组(Sham组)、模型组和干预组,每组8只。模型组和干预组结扎冠脉左前降支后,配合饥饿和力竭游泳的方式构建气虚血瘀型心衰模型,Sham组大鼠冠脉左前降支仅穿线不接扎。干预组予以健心颗粒3.2 g/(kg·d),Sham组和模型组均予以2 mL生理盐水灌胃,每日1次。干预4周后,行右颈动脉插管测定大鼠血流动力学参数[左室收缩末压(LVSP)、左室舒张末压(LVEDP)、左室压力最大上升速率(+dP/dtmax)及左室压力最大下降速率(-dP/dtmax)],测量心脏重量,计算心脏重量指数(HMI),心肌组织行Masson、HE染色分别测定心肌梗死面积百分比、心肌细胞横截面积。留取大鼠心肌组织行CaN的活性检测,免疫组化和Western Blot测定CaNA亚基(CaNA)、CaNB亚基(CaNB)、胞核和胞浆NFATc3及β肌球蛋白重链(β-MHC)、B型利钠肽(BNP)的表达。结果 Sham组大鼠一般情况良好,心肌细胞形态轮廓清晰,排列整齐,少许的炎细胞浸润;模型组大鼠疲乏、萎靡,活动度少,呼吸急促,心肌组织受损严重,心肌细胞轮廓模糊,呈现无序化排列,大量炎症细胞浸润于心肌组织间;与模型组比较,干预组精神状态改善,静息状态下无呼吸急促,活动度增加,心肌形态较模型组完整,排列相对有序,细胞间炎症细胞浸润减少。与Sham组大鼠比较,模型组大鼠LVSP、+dP/dtmax、-dP/dtmax降低,LVEDP、心肌梗死面积百分比、横截面积、HMI、心肌组织CaN活性、β-MHC、BNP蛋白表达、胞核NFATc3蛋白表达以及胞核NFATc3/胞浆NFATc3升高(均P<0.05)。与模型组比较,干预组大鼠LVSP、+dP/dtmax、-dP/dtmax升高,LVEDP、心肌梗死面积百分比、横截面积、HMI、心肌组织CaN活性、β-MHC、BNP蛋白表达、胞核NFATc3蛋白表达以及胞�Objective To observe the effects of Jianxin Granule on myocardial remodeling in rats with heart failure of qi deficiency and blood stasis,and to explore the mechanism of Jianxin Granule on calcineurin(CaN)/nuclear factor c3 of activated T cells(NFATc3)pathway.Methods Twenty-four male SD rats were randomly divided into Sham group,model group and intervention group,8 rats in each group.The rats in the model group and intervention group were undergone ligation of the left anterior descending coronary artery,and the heart failure model of qi deficiency and blood stasis was established by starvation and exhaustive swimming.The left anterior descending coronary artery was only threaded without ligation in the Sham group.The rats in intervention group were given Jianxin Granule 3.2 g·kg-1·d-1 by gastrogavage once a day,and rats in Sham group and model group were given 2 mL normal saline by gastrogavage once a day.After 4 weeks intervention,rats hemodynamic parameters including left ventricular peak systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),maximal rate of the increase of left ventricular pressure(+dP/dtmax)and maximal rate of the decrease of left ventricular pressure(-dP/dtmax)were detected by cannulated though the right carotid artery,the heart weight was measured,the heart mass index(HMI)was calculated,and the myocardial tissue was stained by Masson and HE to measure infarct size and myocardial cross-sectional area respectively.Myocardial tissue was collected to detect the activity of CaN.Immunohistochemistry and Western Blot were used to detect calcineurin A subunit(CaNA),calcineurin B subunit(CaNB),nuclear and cytosol NFATc3,β-myosion heavy chain(β-MHC)and B-type natriuretic peptide(BNP).Results The rats in Sham group were generally in good condition,with clear outline and neat arrangement of cardiomyocytes,and a little inflammatory cell infiltration.The rats in the model group were fatigue,lethargy,low mobility,and shortness of breath,the myocardium was severely damaged,the outline

关 键 词：健心颗粒 气虚血瘀 心力衰竭 心肌重构 钙调磷酸酶/活化T细胞核因子c3 中药复方 

分 类 号：R285.5[医药卫生—中药学]