益气化瘀汤调控miR-532-3p改善阿霉素心脏毒性的机制研究  

Study on the Mechanism of Regulating miR-532-3p in Improving Adriamycin Cardiotoxicity with Yiqi Huayu Decoction

作　　者：陈榕榕 郑平 李得清 杨华 郑泽宇 CHEN Rongrong;ZHENG Ping;LI Deqing;YANG Hua;ZHENG Zeyu(Fuzhou Hospital of Traditional Chinese Medicine Affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou 350001,China;The Second People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou 350000,China)

机构地区：[1]福建中医药大学附属福州中医院,福建福州350001 [2]福建中医药大学附属第二人民医院,福建福州350000

出　　处：《中国中医药信息杂志》2025年第1期128-133,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：福建省自然科学基金(2022J011325)。

摘　　要：目的探究益气化瘀汤调控miR-532-3p改善阿霉素心脏毒性的作用机制。方法25只大鼠随机分为对照组、模型组及益气化瘀汤低、中、高剂量组,每组5只。模型组及益气化瘀汤低、中、高剂量组腹腔注射阿霉素2.5mg/kg建立心肌损伤模型(每周1次,连续8周)。造模同时益气化瘀汤低、中、高剂量组分别予益气化瘀汤2、4、8g/kg灌胃,每日1次,连续8周。超声心动图检测大鼠心功能,ELISA检测血清N端脑钠肽前体(NT-proBNP)含量,HE染色观察心肌组织形态,TUNEL染色检测心肌组织细胞凋亡情况,RT-qPCR检测miR-532-3p基因表达,Westernblot检测心肌组织GATA结合蛋白4(GATA4)、心肌铆定重复序列蛋白(CARP)表达。结果与对照组比较,模型组大鼠左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)明显升高,左室射血分数(LVEF)、左室短轴缩短率(LVFS)明显下降(P<0.05),血清NT-proBNP含量显著升高(P<0.05),心肌细胞重度肥大、排列紊乱,成纤维细胞增生并伴有坏死,心肌细胞凋亡率明显升高(P<0.05),心肌组织miR-532-3p基因表达明显升高(P<0.05),心肌组织GATA4、CARP蛋白表达明显升高(P<0.05);与模型组比较,益气化瘀汤高剂量组大鼠LVESD、LVEDD明显降低(P<0.05),LVEF、LVFS明显升高(P<0.05),益气化瘀汤各剂量组大鼠血清NT-proBNP含量明显降低(P<0.05),心肌细胞损伤、纤维化不同程度改善,心肌细胞凋亡率明显降低(P<0.05),心肌组织miR-532-3p基因表达降低(P<0.05),心肌组织GATA4、CARP蛋白表达下降(P<0.05)。结论益气化瘀汤可拮抗阿霉素心脏毒性,其作用机制可能为调控miR-532-3p表达从而抑制心肌纤维化。Objective To explore the mechanism of regulating miR-532-3p with Yiqi Huayu Decoction to improve adriamycin cardiotoxicity.Methods Totally 25 rats were randomly divided into control group,model group and Yiqi Huayu Decoction low-,medium-and high-dosage groups,with 5 rats in each group.Myocardial injury model was established by intraperitoneal injection of adriamycin 2.5 mg/kg once a week for 8 weeks in model group and Yiqi Huayu Decoction low-,medium-and high-dosage groups.At the same time,Yiqi Huayu Decoction low-,medium-and high-dosage groups were given 2,4,8 g/kg Yiqi Huayu Decoction by gavage respectively,once a day for consecutive 8 weeks.Cardiac function of rats was detected by echocardiography,serum NT-proBNP content was detected by ELISA,morphology of myocardial tissue were observed by HE staining,apoptosis of myocardial tissue was detected by TUNEL staining,miR-532-3p gene expression was detected by RT-qPCR,Western blot was used to detect the expressions of GATA4 and CARP protein.Results Compared with the control group,the left ventricular end systolic diameter(LVESD)and left ventricular end diastolic diameter(LVEDD)of the model group increased significantly,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)significantly decreased(P<0.05),and the serum NT-proBNP content significantly increased(P<0.05),with severe hypertrophy and disordered arrangement of myocardial cells,fibroblast proliferation accompanied by necrosis,and significantly increased apoptosis rate of myocardial cells(P<0.05),the expression of miR-532-3p gene in myocardial tissue significantly increased(P<0.05),and the expressions of GATA4 and CARP proteins in myocardial tissue significantly increased(P<0.05).Compared with the model group,Yiqi Huayu Decoction high-dosage group showed a significant decrease in LVESD and LVEDD(P<0.05),with LVEF and LVFS significantly increased(P<0.05),the content of serum NT-proBNP in Yiqi Huayu Decoction low,medium-and high-dosage groups were significantly decreased(P

关 键 词：益气化瘀汤 心脏毒性 心肌纤维化 miR-532-3p 大鼠 

分 类 号：R285.5[医药卫生—中药学]