人参皂苷Rg2对阿霉素诱导的心脏毒性模型小鼠心肌的保护作用机制研究  

Protective Effect of Ginsenoside Rg2 on Doxorubicin-induced Cardiotoxicity of Mice

作　　者：孟培培 王蓓 刘光 董魁星 麻继臣 MENG Peipei;WANG Bei;LIU Guang;DONG Kuixing;MA Jichen(Hospital of the Joint Logistics Support Force of the Chinese People′s Liberation Army,Shijiazhuang 050000,Hebei,China)

机构地区：[1]中国人民解放军联勤保障部队第九八〇医院,石家庄050000

出　　处：《中西医结合心脑血管病杂志》2023年第19期3513-3520,共8页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：河北省2021年度医学科学研究课题计划(No.20210481)。

摘　　要：目的:探讨人参皂苷Rg2对阿霉素(DOX)诱导的心脏毒性模型小鼠心肌的保护机制。方法:将6~8周龄C57BL/6雄性小鼠60只随机分为对照组、模型组、右美托咪定组、Rg2-L组、Rg2-M组、Rg2-H组和Rg2-H+LY294002组。对照组仅给予无菌生理盐水腹腔注射,模型组、右美托咪定组、Rg2-L组、Rg2-M组、Rg2-H组、Rg2-H+LY294002组小鼠通过腹腔注射20 mg/kg阿霉素建立心脏毒性模型。在模型建立前30 min,右美托咪定组给予50μg/kg右美托咪定腹腔注射,Rg2-L组、Rg2-M组和Rg2-H组分别给予5、10、20 mg/kg人参皂苷Rg2腹腔注射,Rg2-H+LY294002组给予10 mg/kg LY294002、20 mg/kg人参皂苷Rg2腹腔注射,之后每日注射1次,连续干预5 d后处死小鼠。经胸超声心动图检测小鼠左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)和左室短轴缩短率(LVFS)。苏木精-伊红(HE)染色和Masson染色评估心肌组织学病理变化。酶联免疫吸附试验(ELISA)检测血清心肌肌钙蛋白I(cTnI)、心脏型脂肪酸结合蛋白(H-FABP)和肌红蛋白(MB)水平。比色法检测血清肌酸激酶同工酶(CK-MB)水平;试剂盒检测丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)活性。末端脱氧核苷酸转移酶脱氧尿苷三磷酸切口末端标记(TUNEL)试剂盒鉴定心肌细胞凋亡情况。蛋白免疫印迹法(Western Blot)检测相关蛋白的表达。结果:与对照组比较,模型组小鼠LVESD升高,LVEF和LVFS降低(P<0.05);血清cTnI、H-FABP、MB和CK-MB水平增加(P<0.05);心脏纤维化灶形成;MDA含量增加,SOD、ACT和GSH-Px活性降低(P<0.05);心肌细胞凋亡率升高,Caspase-3蛋白水平升高(P<0.05);磷脂酰肌醇3-激酶(PI3K)和蛋白激酶B(AKT)蛋白相对表达下降(P<0.05)。与模型组比较,Rg2-M组和Rg2-H组可明显改善小鼠心功能,降低心肌毒性,减轻心脏氧化应激和细胞凋亡,激活PI3K/AKT通路(P<0.05)。结论:人参皂苷Rg2对�Objective:To investigate the protective effect of ginsenoside Rg2 on doxorubicin(DOX)-induced cardiotoxicity of mice.Methods:Sixty C57BL/6 male mice aged 6 to 8 weeks were randomly divided into control group,model group,dexmedetomidine group,Rg2-L group,Rg2-M group,Rg2-H group,and Rg2-H+LY294002 group.The control group was given sterile saline intraperitoneal injection,mice in model group,dexmedetomidine group,Rg2-L group,Rg2-M group,Rg2-H group,and Rg2-H+LY294002 group were injected with 20 mg/kg DOX intraperitoneally to establish cardiotoxicity model.Thirty minutes before the establishment of the model,dexmedetomidine group was given 50μg/kg intraperitoneal injection;RG2-L group,RG2-M group and RG2-H group were given 5,10,20 mg/kg ginsenoside Rg2 intraperitoneal injection,respectively;Rg2-H+LY294002 group was given 10 mg/kg LY294002 intraperitoneal injection,and then injected once a day.The mice were tested after continuous intervention for 5 days.Left ventricular end diastolic diameter(LVEDD),left ventricular end systolic diameter(LVESD),left ventricular ejection fraction(LVEF),and left ventricular short axis shortening rate(LVFS)were measured by transthoracic echocardiography.Hematoxylin-eosin(HE)and Masson staining were used to evaluate myocardial histological and pathological changes.Serum levels of cardiac troponin I(cTnI),cardiac fatty acid-binding protein(H-FABP),and myoglobin(MB)were detected by enzyme-linked immunosorbent assay(ELISA).Serum creatine kinase isoenzyme(CK-MB)was detected by colorimetry.Serum creatine kinase isoenzyme(CK-MB)was detected by colorimetry.The activities of malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)were detected.The apoptosis of cardiomyocytes was identified by terminal deoxyribonucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)test kit for terminal deoxynucleotide transferase deoxyuridine triphosphate.Western Blot was used to detect the expression of related proteins.Results:Compared with control group,LVES

关 键 词：心脏毒性 人参皂苷RG2 磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT) 氧化应激 细胞凋亡 实验研究 

分 类 号：R285.5[医药卫生—中药学]