摘要
目的制备载葛根素的PEG修饰介孔硅纳米粒(PUE@PEG-MSNs),评价其对急性心肌缺血的保护作用。方法通过缩合反应制备PEG-MSNs,再负载葛根素(PUE),并通过粒径、Zeta电位、透射电子显微镜(TEM)和傅里叶转换红外线光谱(FTIR)等检测表征PUE@PEG-MSNs,采用HPLC测定其载药量和包封率;采用结扎冠状动脉制备60只急性心肌缺血模型大鼠,随机分成6组,每组10只,分别为假手术组、模型组、PUE注射液组和PUE@PEG-MSNs高、中、低剂量组,在结扎后5 min各给药组尾iv给药。监测心电图ST段变化,测定血清肌酸激酶(CK)、乳酸脱氢酶(LDH)、天冬氨酸转氨酶(AST)和丙二醛(MDA)水平,并测量心肌梗死面积。结果 PUE@PEG-MSNs呈规则圆球形,大小均一,粒径约300 nm,电势约-30 m V,且可以负载PUE,载药量和包封率分别为14.7%和67.8%。PUE注射液和PUE@PEG-MSNs均能降低升高的ST段,降低血清中CK、LDH、AST和MDA水平,减少心肌梗死面积;其中PUE@PEG-MSNs中、高剂量组的药效明显强于PUE注射液组。结论 PUE@PEG-MSNs制备成功,对急性心肌缺血大鼠具有良好的保护作用。
Objective To prepare the puerarin-loaded PEGylated mesoporous silica nanoparticles（PUE@PEG-MSNs） and evaluate its protection on the acute myocardial ischemic rats. Methods PEG-MSNs functionalized mesoporous silica nanoparticles were achieved by the condensation method, and then they were loaded by PUE. The morphology of PUE@PEG-MSNs was examined by detection methods of particle diameter, Zeta potential, transmission electron microscope（TEM）, and Fourier transform infrared spectra（FTIR）. Moreover, the drug loading and encapsulation rate were measured by HPLC. Sixty acute ischemic myocardial model rats were prepared by coronary artery ligation, and then they were randomly divided into six groups： Sham, MIRI model, puerarin injection, low-, mid-, and high-dose PUE@PEG-MSNs groups. Different doses of PUE@PEG-MSNs and puerarin injection were given 5 min after the ligation. Monitoring the changes of ST, the blood was collected at the end of reperfusion for detecting the changes of serum creatine kinase（CK）, lactic dehydrogenase（LDH）, aspartate aminotransferase（AST）, and malondialdehyde（MDA）. The myocardial infarct size was also determined. Results PUE@PEG-MSNs presented uniform spherical morphology and particle size distribution. The particle size and Zeta potential was 300 nm and-30 m V respectively. The drug loading and entrapment efficiency was 14.7% and 67.8% respectively. Both puerarin injection and PUE@PEG-MSNs could reduce the ST-elevation of electrocardiogram, decrease the contents of CK, LDH, AST, and MDA, and reduce the myocardial infarct size. The efficacy of mid-and high-dose PUE@PEGMSNs groups was better than that of puerarin injection group. Conclusion PUE@PEG-MSNs were successfully prepared and exerted the protective effects on the acute myocardial ischemic rats.
作者
万小敏
丁宇翔
赵兵杰
胡雄彬
刘新义
WAN Xiao-min;DING Yu-xiang;ZHAO Bing-jie;HU Xiong-bin;LIU Xin-yi(Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, China;Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China)
出处
《中草药》
CAS
CSCD
北大核心
2018年第8期1789-1795,共7页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金资助项目(81673614)
湖南省中医药科技计划(201579)
湖南省卫计委科技项目(C20180059)
湖南省自然科学基金资助项目(14JJ3038)
关键词
PEG修饰介孔硅纳米粒
葛根素
急性心肌缺血
梗死面积
缩合反应
载药量
包封率
血清肌酸激酶
乳酸脱氢酶
天冬氨酸转氨酶
丙二醛
PEGylated mesoporous silica nanoparticles
puerarin
acute myocardial ischemic
infarct size
condensation reaction
drug loading
encapsulation rate
serum creatine kinase
lactate dehydrogenase
aspartate aminotransferase
malonaldehyde
作者简介
万小敏（1982-），男，主管药师，博士，研究方向为药剂学。E-mail：wanxiaomin@csu．edu.cn;通信作者刘新义，博士，主要研究方向为高分子载药系统。Tel：（0731）85292093,E-mail：liuxinyi128@csu．edu．cn.
