土鳖虫活性肽LL8在大鼠体内的药动学及药效学研究  

Pharmacokinetics and pharmacodynamics of bioactive peptide LL8 from Steleophaga plancyi in rats

作　　者：董萍萍 张加余 魏永利[3] 兀琦 徐静 李华健 代龙 王少平 DONG Ping-ping;ZHANG Jia-yu;WEI Yong-li;WU Qi;XU Jing;LI Hua-jian;DAI Long;WANG Shao-ping(School of Pharmacy,Binzhou Medical University,Yantai 264003,China;School of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250300,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250300,China)

机构地区：[1]滨州医学院药学院,山东烟台264003 [2]山东中医药大学药学院,山东济南250300 [3]山东中医药大学附属医院,山东济南250300

出　　处：《中草药》2021年第15期4607-4613,共7页Chinese Traditional and Herbal Drugs

基　　金：山东省青创人才引育团队——中药复杂体系作用模式解析创新研究团队项目(10073004);烟台市校地融合发展中药大健康产业化平台项目(2019XDRHXMPT18);滨州医学院高层次人才科研启动基金资助项目(2019KYQD05,2019KYQD06,BY2018KYQD11);名贵中药资源可持续利用能力建设项目(2060302-1907-08);山东省中药材及饮片标准研究项目(2020-004,2020-201,2020-202,2020-203,2020-204)。

摘　　要：目的研究土鳖虫活性肽LL8在正常大鼠体内的药动学,并考察LL8对高脂血症大鼠模型的影响。方法采用异硫氰酸荧光素(fluorescein isothiocyanate,FITC)对LL8进行N端标记(FITC-LL8),SD大鼠随机分为FITC-LL8高、低剂量(10、5 mg/kg)组,各给药组im相应药物,于不同时间点眼眶取血,采用EnSpire多标记微孔板检测酶标仪,辅以DAS2.0药动学数据处理软件,以偏最小二乘法为计算原则,根据药动学理论得出FITC-LL8在SD大鼠体内的药动学变化。SD大鼠随机分为对照组、模型组、辛伐他汀(200 mg/kg)组、土鳖虫(3 g/kg)组和LL8高、低剂量(50、25 mg/kg)组,采用高脂饲料诱导建立高脂血症大鼠模型,各给药组ig相应药物,1次/d,连续3周,检测各组大鼠血浆中总胆固醇(total cholesterol,TC)、三酰甘油(triglycerides,TG)和低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平;检测各组大鼠肝脏组织中TC和TG水平;采用苏木素-伊红(HE)染色法观察各组大鼠肝组织病理变化。结果高、低剂量LL8在SD大鼠体内的代谢趋势相似。与对照组比较,LL8组大鼠血浆中TG、TC和LDL-C水平显著降低(P<0.05),肝脏组织中TG、TC水平显著降低(P<0.05、0.01)。模型组大鼠肝脏组织内出现明显脂肪空泡与脂滴,各给药组大鼠肝脏脂肪变性明显改善。结论LL8在SD大鼠体内半衰期较短,且能够抑制大鼠肝脏脂肪堆积,具有调血脂作用。Objective To investigate the pharmacokinetics of bioactive peptide LL8 from Tubiechong(Steleophaga plancyi)on normal rats and effect of LL8 on hyperlipidemia rats.Methods Fluorescein isothiocyanate(FITC)was used for N-terminal labeling of LL8.SD rats were divided into high-,low-dose FITC-LL8(10,5 mg/kg)group,rats were im corresponding drugs,blood was taken at different time;EnSpire multi-label microplate inspection system,DAS 2.0 pharmacokinetic data processing software and partial least square calculation principle were used to calculate the pharmacokinetic changes of FITC-LL8 in SD rats.SD rats were randomly divided into control group,model group,simvastatin(200 mg/kg)group,S.plancyi(3 g/kg)group,high-and low-dose LL8(50,25 mg/kg)groups,high fat feed-induced rat models of hyperlipidemia were established.Rats in each administration group were ig corresponding drugs once a day for 3 weeks.Levels of total cholesterol(TC),triglycerides(TG)and low density lipoprotein cholesterol(LDL-C)in plasma of each group were measured;Levels of TC and TG in liver tissues of rats in each group were detected;Hematoxylin-eosin(HE)staining method was used to observe the pathological changes of liver tissues of rats in each group.Results Metabolic trends of SD rats in high-and low-dose LL8 group were similar.Compared with control group,levels of TG,TC and LDL-C in plasma of rats in LL8 group were significantly reduced(P<0.05),levels of TG and TC in liver tissue were significantly reduced(P<0.05,0.01).Obvious fat vacuoles and lipid droplets were appeared in liver tissues of rats in model group,and liver steatosis of rats in each administration group was significantly improved.Conclusion LL8 has a short half-life in SD rats,which can inhibit the accumulation of fat in liver of rats,and has the effect of regulating blood lipids.

关 键 词：土鳖虫活性肽 LL8 肽序分析 异硫氰酸荧光素 高脂血症 

分 类 号：R285.5[医药卫生—中药学]