小红蒜总萘醌抗急性心肌缺血缺氧有效性和安全性初步研究  

Preliminary study on the efficacy of acute myocardial ischemia and its hypoxia or safety of total naphthoquinone in Bulbus Eleutherinis

作　　者：陈婕妤 韦义淇 姜良弟 张书磊 苏靖 邱明丰[1] CHEN Jieyu;WEI Yiqi;JIANG Liangdi;ZHANG Shulei;SU Jing;QIU Mingfeng(School of Pharmacy,Shanghai Jiaotong University,Shanghai 200240,China)

机构地区：[1]上海交通大学药学院,上海200240

出　　处：《沈阳药科大学学报》2025年第4期365-370,共6页Journal of Shenyang Pharmaceutical University

基　　金：转化医学国家重大科技基础设施(上海)开放课题(TMSK-2020-110);上海市科委资助项目(20S21900100)。

摘　　要：目的研究小红蒜中的主要活性部分总萘醌治疗冠心病的有效性和安全性。方法采用细胞毒性实验评估总萘醌体外安全性,对HL-1细胞实施质量浓度为10^(-7)~0.1 mg·mL^(-1)的梯度给药处理,24 h后检测各组细胞活性;采用小鼠急性毒性实验评估总萘醌体内安全性,将CR雄性小鼠分为1 g·kg^(-1)和4 g·kg^(-1)两个剂量组进行单次灌胃给药,1周内观察其生理状况和死亡率;采用HL-1细胞糖氧剥夺(oxygen and glucose deprivation,OGD)模型评估总萘醌体外有效性,对HL-1细胞实施质量浓度为10^(-6)~0.05 mg·mL^(-1)的梯度给药处理,24 h后进行OGD造模,6 h后检测的各组细胞活性;采用大鼠急性心肌缺血模型评估总萘醌体内有效性,将SD雄性大鼠分为100 mg·kg^(-1)和300 mg·kg^(-1)两个剂量组分组连续5 d灌胃给药后造模急性心肌梗死模型,24 h后检测和计算各组大鼠的心肌梗死率和血清中心肌肌钙蛋白T(cardiactroponin-T,cTnT)和肌酸激酶同工酶(creatine kinase MB isoenzyme,CK-MB)的含量。结果细胞毒性实验结果显示,当给药质量浓度超过10^(-2)mg·mL^(-1)时,小红蒜总萘醌对细胞活性有影响。在两组急性毒性实验的小鼠中都没有观察到明显的生理状况变化和死亡。当给药质量浓度在10^(-6)~10^(-3)mg·mL^(-1)的剂量范围内,小红蒜总萘醌减轻了OGD对HL-1细胞的损伤,当给药质量浓度为10^(-4)mg·mL^(-1)时,小红蒜总萘醌的抗缺血缺氧药效最佳。大鼠急性心肌缺血模型有效性实验中,两组大鼠均有降低心肌梗死率的趋势,给药剂量为300 mg·kg^(-1)时可明显降低血清中CK-MB和cTnT水平。结论小红蒜总萘醌对心肌缺血和缺氧有很好的保护作用,且安全性高。Objective To study the efficacy and safety of total naphthoquinone,the main active fraction in Bulbus Eleutherinis for the treatment of coronary heart disease.Methods Cytotoxicity assay was used to evaluate the safety of total naphthoquinone in Bulbus Eleutherinis in vitro,and HL-1 cells were treated with gradient administration at a mass concentration of 10~(-7)~0.1 mg·mL~(-1).The cell viability was assayed after 24 h.The acute toxicity test of mice was used to evaluate the safety of total naphthoquinone in Bulbus Eleutherinis in vivo,ICR male mice were divided into two dose groups for single intragastric administration and the physiology and mortality were observed within 1 week.The HL-1 cell OGD model was used to evaluate the in vitro effectiveness of total naphthoquinone in Bulbus Eleutherinis,and HL-1 cells were treated with gradient administration at a mass concentration of 10~(-6)-0.05 mg·mL~(-1).After 24 h of dosing,OGD models of HL-1 cells were established.Then the cell viability was assayed after 6 h of modelling.A rat model of acute myocardial infarction was used to evaluate the in vivo effectiveness of total naphthoquinone in Bulbus Eleutherinis,SD male rats were divided into two dose groups of 100 mg·kg~(-1) and 300 mg·kg~(-1),and they were intragastrically administered for 5 days.Then,acute myocardial infarction models were induced in these rats.Subsequently,their myocardial infarction rate and the content of cTnT and CK-MB were tested.Results When the total naphthoquinone in Bulbus Eleutherinis was administered at concentrations above 10~(-2) mg·mL~(-1),the total naphthoquinone in Bulbus Eleutherinis affected cell viability.No significant change and mortality were observed in both mouse groups.In the range of 10~(-6) to 10~(-3) mg·mL~(-1),the total naphthoquinone in Bulbus Eleutherinis alleviated OGD damage to HL-1 cells and was most effective when administered at 10~(-4) mg·mL~(-1).Both rats groups showed a tendency to reduce myocardial infarction rate,and the dosage of 300 mg·kg~(-1) sign

关 键 词：小红蒜总萘醌 冠心病 有效性 安全性 

分 类 号：R917[医药卫生—药物分析学]