养心达瓦依米西克蜜膏通过调节VDAC1/NLRP3/Bax/Bcl-2通路改善大鼠心功能  

Yangxin Dawayimicol Honey Ointment Improves Cardiac Function in Rats by Regulating VDAC1/NLRP3/Bax/Bcl-2 Pathway

作　　者：马静卓 姚博 陈恒文[1] 何轩辉 MA Jingzhuo;YAO Bo;CHEN Hengwen;HE Xuanhui(Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;School of Pharmaceutical Sciences,Changchun University of Chinese Medicine,Changchun 130117,China)

机构地区：[1]中国中医科学院广安门医院,北京100053 [2]长春中医药大学药学院,长春130117

出　　处：《中国实验方剂学杂志》2025年第8期115-124,共10页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(82074396);中央高水平中医医院临床科研业务费专项(HLCMHPP2023077);中国中医科学院科技创新工程重点协同攻关项目(CI2023CO22YL);中国中医科学院广安门医院续航人才工程青年拔尖人才培养项目;新疆维吾尔自治区区域协同创新专项(上海合作组织科技伙伴计划及国际科技合作计划)项目(2022E01001)。

摘　　要：目的:探析养心达瓦依米西克蜜膏(YXDW)改善心肌梗死后大鼠心功能的作用及机制。方法:将大鼠分为假手术组、模型组、福辛普利钠片组及YXDW低、中、高剂量组。该实验采用左前降支结扎构建大鼠心梗模型,YXDW组以0.27、0.54、1.08 g·kg^(-1)·d^(-1)剂量灌胃,福辛普利钠片组以3.60 mg·kg^(-1)·d^(-1)剂量灌胃,假手术组及模型组以等量0.5%羧甲基纤维素钠水溶液灌胃处理,连续灌胃4周,观察YXDW对大鼠体征、心脏指数的影响,超声心动图观察心功能变化,病理学检查评价心脏形态变化,酶联免疫吸附测定法(ELISA)评价白细胞介素-1β(IL^(-1)β)、IL-6、氨基末端脑钠肽前体(NT-proBNP)、肿瘤坏死因子-α(TNF-α)等细胞炎症因子的变化,分别采用实时荧光定量聚合酶链反应(Real-time PCR)和蛋白免疫印迹法(Western blot)检测电压依赖性阴离子选择性通道蛋白1(VDAC1)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、线粒体凋亡相关基因B细胞淋巴瘤-2 (Bcl-2)、Bcl-2相关X蛋白(Bax)表达情况。结果:YXDW各组大鼠生存状态普遍有所改善。超声心动图结果显示,与假手术组比较,模型组大鼠心脏左心室射血分数(LVEF)、左室短轴缩短率(LVFS)均显著下降(P<0.01);与模型组比较,各治疗组大鼠LVEF、LVFS均有不同程度增高(P<0.01)。病理学检查显示,与模型组比较,各给药组大鼠心肌细胞变性减少,炎性浸润减轻,肌丝较完整,走形规则,心肌纤维明显减少。电镜结果显示,与模型组比较,YXDW各剂量组心肌细胞线粒体超微结构清楚,膜较完整,嵴较为致密,基质清楚,肌丝及闰盘排列较为规则。ELISA结果显示,与假手术组比较,模型组大鼠血清中IL-6、IL^(-1)β、TNF-α均显著增高(P<0.01);与模型组比较,各给药组大鼠血清中IL-6、IL^(-1)β、TNF-α均显著降低(P<0.01)。与假手术组比较,模型组大鼠血清中NT-proBNP显著升高(P<0.01);与模型组比较,各给药组NT-prObjective:To investigate the effect and mechanism of Yangxin Dawayimicol honey ointment(YXDW)in improving cardiac function in rats after myocardial infarction.Methods:Rats were divided into the sham group,model group,fosinopril sodium tablet group,and YXDW low,medium,and high-dose groups.A rat myocardial infarction model was established by left anterior descending branch ligation.The YXDW groups were administered doses of 0.27,0.54,and 1.08 g·kg^(-1)·d^(-1),while the fosinopril sodium tablet group was given 3.60 mg·kg^(-1)·d^(-1).The sham group and model group were treated with an equal amount of 0.5%sodium carboxymethyl cellulose solution.After continuous gavage for 4 weeks,the effects of YXDW on the signs and cardiac indices of the rats were observed.Echocardiography was used to assess cardiac function,and pathological examination was used to evaluate heart morphology.Enzyme-linked immunosorbent assay(ELISA)was used to assess changes in interleukin-1β(IL^(-1)β),IL-6,N-terminal pro-brain natriuretic peptide(NT-proBNP),and tumor necrosis factor-α(TNF-α).The expression of voltage-dependent anion-selective channel protein 1(VDAC1),nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)was detected by reverse transcription-polymerase chain reaction(Real-time PCR)and Western blot.Results:The survival status of rats in all YXDW groups was generally improved.Echocardiographic results showed that,compared to the sham group,the model group exhibited a significant decrease in left ventricular ejection fraction(LVEF)and left ventricular short axis shortening rate(LVFS),with statistical significance(P<0.01).Compared to the model group,rats in the treatment groups showed varying degrees of improvement in LVEF and LVFS,with statistical significance(P<0.01).Pathological examination revealed reduced myocardial cell degeneration,less inflammatory infiltration,intact myofilaments,regular shape,and significantly fewer myoca

关 键 词：养心达瓦依米西克蜜膏 心肌梗死 电压依赖性阴离子选择性通道蛋白1(VDAC1) NOD样受体热蛋白结构域相关蛋白3(NLRP3) 线粒体凋亡相关基因B细胞淋巴瘤-2(Bcl-2) Bcl-2相关X蛋白(Bax) 

分 类 号：R256[医药卫生—中医内科学] R285.5[医药卫生—中医学] R825.4