杜鹃素通过调控CYP2J2/EETs轴对阿霉素诱导扩张型心肌病大鼠心肌损伤的影响  

Farrerol exhibits the protective effect on myocardial injury via regulating CYP2J2/EETs axis in rats with doxorubicin-induced dilated cardiomyopathy

作　　者：王素侠 刘运阳 刘阳 WANG Su-xia;LIU Yun-yan;LIU Yang(Department of Emergency The Second Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 421001,Hunan Province,China;Department of Cardiovascular Medicine,The Second Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 421001,Hunan Province,China)

机构地区：[1]南华大学衡阳医学院附属第二医院急诊科,湖南衡阳421001 [2]南华大学衡阳医学院附属第二医院心血管内科,湖南衡阳421001

出　　处：《中国临床药理学杂志》2024年第22期3296-3300,共5页The Chinese Journal of Clinical Pharmacology

基　　金：湖南省自然科学基金青年基金资助项目(2019JJ50532)。

摘　　要：目的探讨杜鹃素对阿霉素(Dox)诱导扩张型心肌病(DCM)大鼠心肌损伤的影响。方法通过腹腔注射2.5mg·kg^(-1)Dox构建DCM大鼠模型。将大鼠随机分成正常组(腹腔注射等量0.9%NaCl)、模型组(构建DCM大鼠模型)、低剂量实验组(12.5mg·kg^(-1)·d^(-1)杜鹃素灌胃)、高剂量实验组(50mg·kg^(-1)·d^(-1)杜鹃素灌胃)和联合组(50mg·kg^(-1)·d^(-1)杜鹃素灌胃+1.5mg·kg^(-1)·d^(-1)C26灌胃)。检测大鼠心功能,用原位末端标记法检测凋亡率,用酶联免疫吸附试验(ELISA)法检测大鼠心肌组织中环氧二十碳三烯酸(EETs)产物11,12-EET和14,15-EET水平,用蛋白质印迹法检测心肌组织中细胞色素P450环氧合酶2J2(CYP2J2)蛋白的表达水平。结果正常组、模型组、低剂量实验组、高剂量实验组和联合组的左心室舒张末期内径(LVEDD)分别为(5.44±0.15)、(6.23±0.36)、(6.14±0.58)、(5.66±0.22)和(6.16±0.35)mm,左心室射血分数(LVEF)分别为(83.36±2.05)%、(59.66±5.93)%、(56.63±3.20)%、(74.67±3.33)%和(61.95±5.38)%,肌酸激酶(CK)水平分别为(346.10±49.51)、(874.50±85.52)、(860.30±46.38)、(371.20±50.83)和(789.44±86.48)U·L^(-1),心肌细胞凋亡率分别为(2.34±0.91)%、(20.11±3.85)%、(18.94±1.65)%、(10.64±1.23)%和(17.56±2.02)%,11,12-EET水平分别为(28.79±4.21)、(9.69±3.43)、(10.71±3.89)、(21.85±5.46)和(12.94±4.60)pg·mg^(-1),14,15-EET水平分别为(33.12±3.47)、(12.75±4.34)(13.27±7.20)、(25.18±6.21)和(16.25±2.08)pg·mg^(-1),CYP2J2蛋白表达水平分别为1.20±0.08、0.19±0.04、0.19±0.05、0.85±0.05和0.33±0.05。模型组的上述指标与正常组比较,高剂量实验组的上述指标与模型组比较,联合组的上述指标与高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.01)。结论杜鹃素可以改善Dox致DCM大鼠心肌损伤,其作用机制可能与激活CYP2J2/EETs通路有关。Objective To investigate the effect of Farrerol on the myocardial injury induced by doxorubicin(Dox)in rats with dilated cardiomyopathy(DCM).Methods SD rats were given intraperitoneal injection of 2.5 mg·kg^(-1)Dox to establish the DCM model.The rats were randomly divided into normal group(given the same amount of 0.9%NaCl by gavage),model group(establish the DCM model),experimental-L group(given 12.5 mg·kg^(-1)·d^(-1)farrerol by gavage),experimental-H group(given 50 mg·kg^(-1)·d^(-1)farrerol by by gavage),combine group(given 50 mg·kg^(-1)·d^(-1)farrerol+1.5 mg·kg^(-1).d^(-1)C26 by gavage).Cardiac function was detected after drug intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of 11,12-EET and 14,15-EET,the products of epoxyeicosatrienoic acids(EETs)in myocardial tissue.Western blot was used to detect the protein expression of cytochrome P450 cyclooxygenase 2J2(CYP2J2)in myocardial tissue.Results The left ventricular end diastolic diameter(LVEDD)of normal group,model group,experimental-L,-H groups and combine group were(5.44±0.15),(6.23±0.36),(6.14±0.58),(5.66±0.22)and(6.16±0.35)mm;the left ventricular ejection fraction(LVEF)were(83.36±2.05)%,(59.66±5.93)%,(56.63±3.20)%,(74.67±3.33)%and(61.95±5.38)%;the creatine kinase(CK)levels were(346.10±49.51),(874.50±85.52),(860.30±46.38),(371.20±50.83)and(789.44±86.48)U·L^(-1);the apoptosis rates of cardiomyocytes were(2.34±0.91)%,(20.11±3.85)%,(18.94±1.65)%,(10.64±1.23)%and(17.56±2.02)%;the 11,12-EET levels were(28.79±4.21),(9.69±3.43),(10.71±3.89),(21.85±5.46)and(12.94±4.60)pg·mg^(-1);the 14,15-EET levels were(33.12±3.47),(12.75±4.34),(13.27±7.20),(25.18±6.21)and(16.25±2.08)pg·mg^(-1);the CYP2J2 protein expression levels were 1.20±0.08,0.19±0.04,0.19±0.05,0.85±0.05 and 0.33±0.05,respectively.The differences of above indicators were statistically significant between the model group and the normal group,between the experimental-H group and the model group,as well as between the combine group a

关 键 词：杜鹃素 扩张型心肌病 心肌损伤 细胞色素P450环氧合酶2J2/环氧二十碳三烯酸通路 

分 类 号：R28[医药卫生—中药学]