黄酒多酚对阿霉素心脏毒性的保护作用研究  

Yellow wine polyphenolic compounds prevent doxorubicin cardiac toxicity through up-regulation of peroxisome proliferator-activated receptor-gamma

作　　者：陆燕[1] 韩敏[1] 孟立平[2] LU Yan;HAN Min;MENG Liping(Department of Radiology,Shaoxing People's Hospital,Shaoxing 312000,China;不详)

机构地区：[1]绍兴市人民医院放射科,321000 [2]绍兴市人民医院心内科,321000

出　　处：《浙江医学》2023年第20期2136-2141,I0003,共7页Zhejiang Medical Journal

基　　金：国家自然科学基金项目(81873120)。

摘　　要：目的探讨黄酒多酚(YWPC)对阿霉素(Dox)心脏毒性的保护作用及其可能的机制。方法将32只Wistar大鼠按随机数字表法分为对照组(正常饮食)、Dox组(正常饮食+腹腔注射Dox)、Dox+YWPC组(正常饮食+腹腔注射Dox+YWPC灌胃)、Dox+YWPC+过氧化物酶体增殖物激活受体-γ(PPAR-γ)拮抗剂GW9662组(正常饮食+腹腔注射Dox+YWPC灌胃+腹腔注射GW9662),每组各8只。Dox每2 d腹腔注射3 mg/kg 1次;YWPC每天灌胃30 mg/kg;GW9662在Dox治疗前30 min腹腔注射1 mg/kg。干预4周后行心电图检查,记录心率,心脏超声检查评估心脏结构和功能;处死大鼠后取心脏组织采用HE和Masson染色检测心脏纤维化程度,用电镜观察心肌细胞的超微结构。采用免疫组化和Western blot法检测心脏成纤维细胞活化标志物肌动蛋白α(SMα)、转录因子21(Tcf21)、基质金属蛋白酶-2(MMP-2)以及PPAR-γ的表达。结果与对照组比较,Dox组大鼠心脏功能降低,心脏纤维化程度增加,心肌细胞线粒体数量增加,肌丝排列紊乱,SMα、Tcf21、MMP-2表达增加,PPAR-γ表达减少(均P<0.05)。与Dox组比较,Dox+YWPC组大鼠心脏功能增加,心脏纤维化程度降低,心肌细胞线粒体数量降低,肌丝排列紊乱情况好转,SMα、Tcf21、MMP-2表达减少,PPAR-γ表达增加(均P<0.05)。与Dox+YWPC组比较,Dox+YWPC+GW9662组大鼠心脏功能降低,心脏纤维化程度增加,心肌细胞线粒体数量增加,肌丝排列紊乱,SMα、Tcf21、MMP-2表达增加,PPAR-γ表达减少(均P<0.05)。结论YWPC能够抑制Dox引起的心脏成纤维细胞活化,缓解Dox引起的心脏纤维化程度,其心脏保护作用可能与增加PPAR-γ表达有关。Objective To investigate the effect of yellow wine polyphenolic compounds(YWPC)on doxorubicin(Dox)cardiotoxicity and related mechanisms.Methods Thirty-two rats were randomly divided into four groups(n=8 per group).No special treatment was given to rats in control group;intraperitoneal injection of Dox(3 mg/kg)was given to Dox group;intraperitoneal injection of Dox(3 mg/kg)and gavage of YWPC(30 mg/kg)were given to Dox+YWPC group;and intraperitoneal injection of Dox(3 mg/kg),gavage of YWPC(30 mg/kg)and intraperitoneal injection of peroxisome proliferator activated receptor-γ(PPAR-γ)GW9662(1 mg/kg,30 min before Dox treatment)were given to Dox+YWPC+GW9662 group.After treatment for 4 weeks,the electrocardiogram was performed and the heart rate was recorded;then rats were sacrificed and heart tissue samples were obtained,cardiac structure and function were analyzed using echocardiography;cardiac fibrosis in hear tissue was examined with HE and Masson staining;the ultrastructure of cardiomyocytes were observed with electron microscopy;the expression of fibroblast activation markers smooth muscle actinα(SMα),transcription factor 21(Tcf21),matrix metalloproteinases-2(MMP-2),and PPAR-γwas determined with immunohistochemical analysis and Western blot.Results Compared with the control group,the cardiac function of rats in Dox group was decreased,the number of mitochondria in myocardial cells increased,and the arrangement of myofilaments was disordered,the degree of cardiac fibrosis was aggravated,the expression of SMα,Tcf21 and MMP-2 was up-regulated,and the expression of PPAR-γwas down-regulated(all P<0.05).Compared with Dox group,the cardiac function of rats in Dox+YWPC group was increased,the degree of cardiac fibrosis was attenuated,the number of mitochondria in myocardial cells decreases,and the disorder of myofilament arrangement was alleviated,the expression of SMα,Tcf21 and MMP-2 was down-regulate,and the expression of PPAR-γwas up-regulated(all P<0.05).Compared with Dox+YWPC group,the cardiac function of ra

关 键 词：黄酒多酚 阿霉素 心脏成纤维细胞 过氧化物酶体增殖物激活受体-Γ 毒性 心脏纤维化 

分 类 号：R96[医药卫生—药理学]