葛根素脂质微球注射液、葛根素注射液药动学及对局灶性脑缺血再灌注大鼠的神经保护作用的比较研究  

Comparative Study of the Pharmacokinetics of Puerarin Lipid Microsphere Injection and Puerarin Injection and Neuroprotective Effects on Rats with Focal Cerebral Ischemia and Reperfusion

作　　者：汪春燕 陈绪龙 汪新娌 徐希强 周爱鲜 梁新丽[1] Wang Chunyan;Chen Xulong;Wang Xinli;Xu Xiqiang;Zhou Aixian;Liang Xinli(Jiangxi University of Traditional Chinese Medicine,Nanchang 330004;Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine,Nanchang 330004)

机构地区：[1]江西中医药大学,南昌330004 [2]江西中医药大学附属医院,南昌330004

出　　处：《中药药理与临床》2021年第3期67-71,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：江西省卫生计生委科技计划(编号:20181140);九江市科技计划(编号:2017109)。

摘　　要：目的:比较研究自制葛根素脂质微球注射液与葛根素注射液的大鼠药动学及对局灶性脑缺血再灌注大鼠的神经保护作用。方法:大鼠分别单次静脉给予50 mg/kg的葛根素脂质微球注射液和葛根素注射液,观察药物对大鼠的药代动力学特征。线栓法建立大鼠局灶性脑缺血再灌注模型,随机分模型对照组、葛根素脂质微球注射液25、50、100 mg/kg、葛根素注射液50 mg/kg组,术后立即尾静脉注射各组药物,另设假手术组。采用Garcia评分评估大鼠神经功能,氯化三苯基四氮唑(TTC)染色测定脑梗死体积,ELISA法检测脑组织匀浆中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子α(TNF-α)、细胞间黏附分子1(ICAM-1)水平。结果:与葛根素注射液相比,葛根素脂质微球注射液在大鼠体内的生物利用度(AUC)、达峰浓度(Cmax)、药物半衰期(t1/2)和滞留时间(MRT)显著高于葛根素注射液(P<0.05)。与假手术组相比,模型对照组的脑组织含水量、脑梗死面积百分比、ICAM-1、IL-6、IL-1β、TNF-α水平均显著升高(P<0.01)。葛根素脂质微球注射液各剂量组及葛根素注射液组均能明显改善大鼠神经功能,明显降低脑组织含水量、脑梗死面积百分比、ICAM-1、IL-6、IL-1β、TNF-α水平(P<0.05或P<0.01)。相同剂量的葛根素脂质微球注射液与葛根素注射液相比较,葛根素脂质微球注射液对局灶性脑缺血再灌注损伤保护作用显著(P<0.05)。结论:葛根素脂质微球注射液可提高葛根素入血浓度及生物利用度;葛根素脂质微球注射液和葛根素注射液对局灶性脑缺血再灌注损伤均有较好的保护作用,相同剂量葛根素脂质微球注射液对局灶性脑缺血再灌注大鼠的神经保护作用优于葛根素注射液组。Objective:To compare the pharmacokinetics of self-made Puerarin Lipid Microsphere Injection(PLMI)and Puerarin Injection(PI)and their neuroprotective effects on rats with focal cerebral ischemia and reperfusion.Methods:Rats received a single intravenous injection of 50 mg/kg PLMI or PI and the pharmacokinetic behaviors were observed.After the rat model of focal cerebral ischemia and reperfusion was established by suture method,rats were randomly divided into a sham operation group,a model control group,high-(100 mg/kg),medium-(50 mg/kg),and low-dose(25 mg/kg)PLMI groups,and a PI(50 mg/kg)group.After modeling,rats were injected with corresponding drugs through the tail vein immediately.Garcia test was used to evaluate rat nerve function.Triphenyltetrazolium chloride(TTC)staining was adopted to determine cerebral infarct volume,and the levels of interleukin-6(IL-6),IL-1β,tumor necrosis factorα(TNF-α),and intercellular adhesion molecule 1(ICAM-1)in brain tissue homogenate were detected by the enzyme-linked immunosorbent assay(ELISA).Results:The bioavailability(AUC),the peak concentration(Cmax),the half-life of drug(t1/2),and the retention time(MRT)were higher in the PLMI group than in the PI group(P<0.05).Compared with the sham operation group,the model control group showed increased water content in the brain tissue,cerebral infarct size(percentage),the levels of ICAM-1,IL-6,IL-1β,and TNF-α(P<0.01).The PLMI groups and the PI group showed improved nerve function of rats,reduced water content in the brain tissue,dwindled cerebral infarct size,and down-regulated levels of ICAM-1,IL-6,IL-1β,and TNF-α(P<0.05 or P<0.01).Compared with the PI group,the medium-dose PLMI group showed a significant protective effect against focal cerebral ischemia-reperfusion injury(P<0.05).Conclusion:PLMI can increase the blood concentration of puerarin and improve its bioavailability.Both PLMI and PI have good protective effects against focal cerebral ischemia-reperfusion injury,while PLMI is superior to PI at the same dose.

关 键 词：葛根素 脂质微球 药代动力学 局灶性脑缺血再灌注 炎症因子 

分 类 号：R285.5[医药卫生—中药学]