吴茱萸碱衍生物纳米粒的多功能性药效学研究  

Pharmacodynamics of multifunctional evodiamine butyryl derivative-loaded lipid nanoparticles

作　　者：杨兰 陈冉 施宇涛 张景勍[1] 胡雪原[1] Yang Lan;Chen Ran;Shi Yutao;Zhang Jingqing;Hu Xueyuan(Medicine Engineering Research Center,College of Pharmacy of Chongqing Medical University)

机构地区：[1]重庆医科大学药学院、重庆高校药物工程研究中心,重庆400016

出　　处：《重庆医科大学学报》2020年第2期217-221,共5页Journal of Chongqing Medical University

基　　金：国家自然科学基金资助项目(编号:30973645);重庆市研究生科研创新资助项目(编号:CYS17172);重庆医科大学大学生科学研究与创新实验资助项目(编号:201724)。

摘　　要：目的:研究吴茱萸碱丁酰基衍生物(evodiamine butyryl derivative,EAB)和吴茱萸碱丁酰基衍生物固体脂质纳米粒(evodiamine butyryl derivative-loaded lipid nanoparticles,EABLN)在大鼠体内的多功能性药效学行为。方法:采用薄膜超声法制备EABLN,对制剂的外观、粒径、电位和包封率进行检测。将32只SD雄性大鼠随机分为正常组、模型组、EAB治疗组、EABLN治疗组,每天监测大鼠的体质量变化。治疗组先连续口服灌胃给药治疗1周后,再口服灌胃次黄嘌呤并皮下注射氧嗪酸钾后成功造就了大鼠的高尿酸血症模型,检测血清中尿酸(uric acid,UA)、血肌酐(serum creatinine,CR)、尿素氮(usea nitrogen,BUN)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein,LDL)、高密度脂蛋白(high density lipoprotein,HDL)、谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)水平,并进行心、肝、脾、肺、肾、脑组织病理学检查。结果:电镜结果显示,EABLN制备成功。体质量曲线结果显示不同组别对大鼠体质量影响未见不同,但4个组别在7个时间点上体质量有差异。生化指标结果显示,模型组UA、CR、BUN水平明显高于其他各组,差异有统计学意义(F=20.080,F=8.459,F=7.169;P=0.000,P=0.007,P=0.012);4组间的血清ALT、AST水平均无统计学差异(F=1.701,F=3.528;P=0.244,P=0.068)。4组间的TC、TG、LDL和HDL水平均无统计学差异(F=3.069,F=0.398,F=0.191,F=3.291;P=0.091,P=0.758,P=0.899,P=0.079)。病理组织学检查表明,模型组的肾单位完整性被严重破坏,而经EABLN治疗后,逆转了高尿酸血症对肾脏的损害,且EABLN不会对心、肝、脾、肺、脑造成病变。结论:EABLN首次被发现能用于治疗高尿酸血症及其所引发的并发症。Objective:To study the pharmacodynamics of multifunctional evodiamine butyryl derivative(EAB) and evodiamine butyryl derivative-loaded lipid nanoparticles(EABLNs) in rats. Methods:EABLNs were prepared by the film ultrasound method;the appearance,particle size,potential,and encapsulation efficiency of EABLNs were measured. Thirty-two male Sprague-Dawley rats were randomly divided into normal group,model group,EAB treatment group,and EABLNs treatment group;the body weight changes of the rats were monitored daily. After continuous administration by oral gavage for 1 week,followed by administration of hypoxanthine by oral gavage and subcutaneous injection of potassium oxonate,the rat model of hyperuricemia was successfully established. The rats were tested for serum levels of uric acid(UA),creatinine(CR),urea nitrogen(BUN),total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL),high-density lipoprotein(HDL),alanine aminotransferase(ALT),and aspartate aminotransferase(AST). Meanwhile,histopathological examinations were performed on the heart,liver,spleen,lung,kidney,and brain of the rats. Results:Electron microscopy showed that EABLNs were successfully prepared. Body weight curves showed that there were no differences(except for the results measured at 7 time points) in body weight between the four different groups. Biochemical analysis showed that,the levels of UA,CR,and BUN were significantly higher in the model group than in the other three groups(F =20.080,F =8.459,F =7.169;P =0.000,P =0.007,P =0.012);there were no significant differences between the four groups in serum levels of ALT or AST(F=1.701,F=3.528;P=0.244,P=0.068),or serum levels of TC,TG,LDL,or HDL(F=3.069,F=0.398,F=0.191,F=3.291;P=0.091,P=0.758,P=0.899,P=0.079). Histopathological examinations showed that the integrity of the renal units in the model group was seriously damaged,but the damage of the kidney induced by hyperuricemia was reversed by EABLNs,and EABLNs did not cause damage to the heart,liver,spleen,lung,or brain. Conclusion:It is

关 键 词：吴茱萸碱丁酰基衍生物 吴茱萸碱丁酰基衍生物固体脂质纳米粒 药效学 

分 类 号：R944.9[医药卫生—药剂学]