金纳米颗粒介导阿托伐他汀载体的构建及其对心肌再灌注损伤影响的研究  

Protective effects of atorvastatin-loaded gold nanoparticles on myocardial ischemia-reperfusion injury

作　　者：朱琳[1] 李屹 张蛟 俞泓 张晓静 刘惠亮[1] ZHU Lin;LI Yi;ZHANG Jiao;YU Hong;ZHANG Xiao-jing;LIU Hui-liang(Institute of Cardiology,the Third Medical Center of PLA General Hospital,Anhui Medical University,Beijing 100039,China;Dept of Cardiology,the Third Medical Center of PLA General Hospital,Beijing 100039,China;Dept of Cardiology,Beijing Electric Power Hospital,Beijing 100073,China)

机构地区：[1]安徽医科大学解放军总医院第三医学中心临床学院心脏病研究所,北京100039 [2]解放军总医院第三医学中心心内科,北京100039 [3]国家电网公司北京电力医院心内科,北京100073

出　　处：《中国药理学通报》2020年第9期1233-1240,共8页Chinese Pharmacological Bulletin

基　　金：国家自然青年科学基金资助项目(No 81700276)。

摘　　要：目的探究“金纳米颗粒-阿托伐他汀”(“AuNPs-Ator”)药物复合载体的构建方法及表征,并在体外对其抗心肌再灌注损伤(myocardial ischemia reperfusion injury,MIRI)的作用进行研究。方法DLS验证“AuNPs-Ator”的构建;UV-Vis评估“AuNPs-Ator”中阿托伐他汀(Atorvastatin,Ator)的搭载量及释放速率;CCK-8检测“AuNPs-Ator”的生物相容性;DHE染色、qRT-PCR及Western blot检测“AuNPs-Ator”药物复合载体的抗ROS水平、调节miR-199a-5p/GSK-3β通路相关基因/蛋白及凋亡蛋白的表达结果。结果AuNPs的粒径及电势分别为5~10 nm、-11 mV,Ator加载后的粒径及电势则分别为20~55 nm、-7 mV。药物复合载体中Ator的搭载量为60%,室温静置条件下,10 h达到药物的稳定释放状态,48 h内累计药物释放率为88.36%。“AuNPs-Ator”药物复合载体对心肌细胞保护作用优于单一材料的处理组。结论“AuNPs-Ator”药物复合载体具有较高的Ator搭载量及药物缓释作用。适宜的浓度作用下,AuNPs与Ator具有协同抗MIRI作用,该研究为金纳米颗粒用于再灌注损伤的药物/基因转运治疗提供新的策略。Aim To investigate the constrution and characterization of atorvastatin-loaded gold nanoparticles and then research synergy with AuNPs and Atorin the alleviation of myocardial ischemia/reperfusion injury.Methods DLS were measured to make sure that“AuNPs-Ator”were successfully constructed.We used UV-Vis to assess the drug loading amount and release rate of Atorvastatin indrug carrier,and further evaluated its biocompatibility ex vivo with CCK-8 detection.We used dyeing of DHE,qRT-PCR and Western blot to demonstrate the protective effects of drug carrier and its adjustment mechanism of miR-199a-5p/GSK-3βin a myocardial ischemia-reperfusion injury(I/R)model.Results The average particle size and zeta potential of AuNPs were in the range of 5~15 nm and-11 mV respectively,and the particle size and zeta potential of the drug carrier were ranged from 20 to 55 nm and-7 mV,respectively.The nano-complex exhibited highdrug loading which was 60%,the in vitro drug release behavior of the drug carrier was stable at room temperature after 10 hours.The cumulative drug release rate was up to 88.36%after 48 hours.The drug carrier had better protective effect on injured myocardial cell than single material treatment grouphad.Conclusions The“AuNPs-Ator”nano-complex exhibits high loading and slow release rate of atorvastatin.Under suitable concentration conditions,AuNPs and atorvastatin produce a synergistic protective effect on MIRI,and AuNPs offer a new effective strategy for drug and gene delivery for curing MIRI.

关 键 词：纳米材料 他汀 再灌注损伤 心肌凋亡 氧化性损伤 miR-199a-5p/GSK-3β 

分 类 号：R318.08[医药卫生—生物医学工程] R329.25[医药卫生—基础医学]