钩藤碱固体脂质纳米粒的毒性研究  

Study on the toxicity of solid lipid nanoparticles of rhynchophylline in rats

作　　者：王盟[1] 田宝成[2] 田桂芹[3] 商林林[4] 张长远[1] 赵亚鑫[1] WANG Meng;TIAN Baocheng;TIAN Guiqin;SHANG Linlin;ZHANG Changyuan;ZHAO Yaxin(Department of Medicine,Jining No.1 Peopled Hospital,Jining 272000,China;College of Pharmacy,Binzhou Medical College,Yantai 264000,China;Department of Pharmacy,Jining Hospital for Infectious Diseases,Jining 272000,China;Department of Pharmacy,Jining No.2 People's Hospital Jining 272000,China)

机构地区：[1]济宁市第一人民医院医务部,济宁272000 [2]滨州医学院药学院,烟台264000 [3]济宁市传染病医院药剂科,济宁272000 [4]济宁市第二人民医院药剂科,济宁272000

出　　处：《西北药学杂志》2018年第1期50-54,共5页Northwest Pharmaceutical Journal

基　　金：山东省自然科学基金项目(编号:2016ZRA08005);山东省中医药科技发展计划项目(编号:2015-443);济宁市中医药科技项目(编号:ZYY2015018);济宁医学院校级科研项目(编号:JY2015KJ027)

摘　　要：目的考察钩藤碱固体脂质纳米粒的急性毒性和长期毒性,并与钩藤碱缓释滴丸的毒性进行比较。方法小鼠1次性灌胃给药钩藤碱固体脂质纳米粒和钩藤碱缓释滴丸,观察14d内动物毒性反应和死亡情况,并计算其LD50;将100只Wistar大鼠随机分为空白对照组、钩藤碱固体脂质纳米粒高、低剂量组和钩藤碱缓释滴丸高、低剂量组,各20只。大鼠连续灌胃12周,每天观察大鼠的一般状态,每2周记录1次体质量。给药12周后和停药2周后检测大鼠血液学指标和血液生化指标,计算脏体比值,同时对重要脏器进行病理学检查。结果测得钩藤碱固体脂质纳米粒的LD50为2 125.5 mg·kg^(-1),95%CI为2 019.2~2 231.6mg·kg^(-1),钩藤碱缓释滴丸的LD50为1 900.7mg·kg^(-1),95%CI为1651.8~2 167.9mg·kg^(-1);连续灌胃给药12周后,钩藤碱缓释滴丸高剂量组大鼠饮食不佳,体质量增长缓慢,大鼠的ALT、AST和ALP值升高,脏体比值升高,肝脏部分出现变性、灶状坏死灶。钩藤碱固体脂质纳米粒剂量组大鼠各项指标无明显变化。结论固体脂质纳米粒剂型可改善钩藤碱对动物肝脏的毒性反应。To study the acute toxicity and long term toxicity of the solid lipid nanoparticles of rhynchophylline,and to compare the toxicity of the sustained-release tablets of rhynchophylline.After a single intragastric administration of rhynchophylline solid lipid nanoparticles and rhynchophylline sustained-release pills,the animal toxicity and death rate were observed within 14 days and the LD50 was calculated.100 Wistar rats were randomly divided into blank control group,rhynchophylline solid lipid nanoparticles high and low dose groups,rhynchophylline sustained-release dropping pills,the low dose group,20 rats in each group.The rats were continuously fed for 12 weeks.The general state of the rats was observed every day and the weight was recorded every 2 weeks.After 12 weeks of administration,and after stopping for a period of 2 weeks,the blood index,blood biochemical index,and the ratio of body to body were calculated.The LD50value of solid lipid nanoparticles of rhynchophylline was 2 125.5 mg.kg 1.The 95%confidence interval was 2 019.2-2 231.6 mg.kg 1;The LD50 value of rhynchophylline sustained-release pill was 1 900.7 mg.kg 1.The 95%confidence interval was 1 651.8-2 167.9 mg.kg 1.After continuous intragastric administration for 12 weeks,rhynchophylline sustained-release pill high dose group showed a poor diet,a slow increase of body weight,ALT,A ST,ALP,and the ratio of liver viscera increased.Also partial hepatic degeneration and focal necrosis were appeared.No significant change was found in the index of the rats in the dose group of solid lipid nanoparticles.The solid lipid nanoparticles can improve the toxic reaction of uncaria to animal liver.

关 键 词：钩藤碱 固体脂质纳米粒 毒性 

分 类 号：R965[医药卫生—药理学]