土鳖虫活性肽DP17在大鼠体内的药效学及药动学研究  

Pharmacodynamics and pharmacokinetics study of the bioactive peptide DP17 from Steleophaga Plancyi in rats

作　　者：王东波 卢立明[2] 张晓琪 王少平 满玉清[2] WANG Dongbo;LU Liming;ZHANG Xiaoqi;WANG Shaoping;MAN Yuqing(School of Pharmacy,Binzhou Medical University,Yantai 264003,Shandong,P.R.China;Binzhou Medical University Hospital,Bingzhou 256603,Shandong,P.R.China)

机构地区：[1]滨州医学院药学院,山东烟台264003 [2]滨州医学院附属医院,山东滨州256603

出　　处：《滨州医学院学报》2025年第1期58-63,69,共7页Journal of Binzhou Medical University

摘　　要：目的研究土鳖虫活性肽DP17对急性血瘀大鼠的治疗作用以及不同给药途径下DP17在正常SD大鼠体内的吸收代谢行为。方法将SD大鼠随机分为正常组、模型组、尿激酶阳性组(100000 U/kg)、血栓通胶囊组(5 g/kg)、土鳖虫药材组(3.75 g/kg)、DP17高剂量组(50 mg/kg)、DP17低剂量组(25 mg/kg)。除正常组外,其他各组大鼠皮下注射1%盐酸肾上腺素,每日2次,在第一次皮下注射2 h后,将大鼠置于4℃冰水浴强制游泳5 min,持续8 d,建立急性血瘀模型。第9 d后每天在第2次注射盐酸肾上腺素1 h后给药。土鳖虫药材组、血栓通胶囊组采用灌胃方式给药,其余各给药组均采用肌内注射(大腿后侧与臀部之间)方式给药,给药持续8 d,采用血液流变仪和全自动凝血测试仪测定各组大鼠的血液流变学指标以及凝血指标。采用异硫氰酸荧光素(FITC)对DP17进行N端标记(FITC-DP17),建立大鼠血浆中FITC-DP17的含量测定方法,考察肌内注射和尾静脉注射两种给药途径下DP17在正常大鼠体内的药代动力学参数。结果与模型组比较,DP17组(高、低剂量)的大鼠的全血黏度和红细胞压积均明显下降(P<0.05),并且凝血酶原时间、活化部分凝血活酶时间、凝血酶时间和纤维蛋白原-凝血酶时间均明显延长(P<0.05)。药动学结果显示,肌内注射途径下DP17(20、10 mg/kg)代谢速度较慢,但生物利用度较低。尾静脉注射途径下DP17(20、10 mg/kg)在体内吸收较快,但代谢也较快。结论土鳖虫活性肽DP17能够有效地降低血液黏稠度,改善血液黏滞状态。本研究进一步验证了DP17在体内具有生物利用度低等问题,这为下一步应用材料学对其结构优化以及将来土鳖虫活性肽制剂的开发提供了借鉴与参考。Objective To study the therapeutic effect of the bioactive peptide DP17 from Steleophaga Plancyi on acute blood stasis rats and the absorption and metabolism of DP17 in normal SD rats under different administration routes.Methods SD rats were randomly divided into the control group,the model group,the urokinase positive group(100000 U/kg),the Xueshuantong capsule group(5 g/kg),the Steleophaga Plancyi group(3.75 g/kg),the DP17 high dose group(50 mg/kg)and the DP17 low dose group(25 mg/kg).Except for the control group,the rats in the other groups were subcutaneously injected with 1%adrenaline hydrochloride twice a day.Two hours after the first subcutaneous injection,the rats were forced to swim in ice water bath at 4℃for 5 minutes for 8 days to establish an acute blood stasis model.On the 9th day,the drug was administered 1 hour after the second injection of epinephrine hydrochloride.The Steleophaga Plancyi group and the Xueshuantong capsule group were administered by intragastric administration,and the other groups were administered by intramuscularly injected(between the back of the thigh and the buttocks).The administration lasted for 8 days.The hemorheology indexes and coagulation indexes of rats in each group were measured by hemorheology instrument and automatic coagulation tester.FITC was used to label the N-terminal of DP17,and the methodology for the determination of FITC-DP17 in rat plasma was established.Investigating the pharmacokinetic parameters of DP17 in normal rats under two administration routes of intramuscularly injected and tail vein injection were investigated.Results Compared with those in the model group,the WBV and the PCV of rats in the DP17 group(high and low doses)were significantly decreased(P<0.05),and PT,APTT,TT and Fibg-TT were significantly prolonged(P<0.05).The pharmacokinetic results showed that DP17(20,10 mg/kg)had a slower metabolic rate in the intramuscularly injected pathway,but the bioavailability was lower.DP17(20,10 mg/kg)in the pathway of tail vein injection were absorbe

关 键 词：土鳖虫活性肽 急性血瘀 药动学 肌内注射 尾静脉注射 

分 类 号：R285[医药卫生—中药学]