三七总皂苷不同口服制剂对急性血瘀模型大鼠的药效学比较研究  

Pharmacodynamic comparison of Panax Notoginseng Saponins with different oral preparations on acute blood stasis model rats

作　　者：王朔 仇坤 周利梅 陈明 赖树生 梁峰 尉小慧[1] WANG Shuo;QIU Kun;ZHOU Limei;CHEN Ming;LAI Shusheng;LIANG Feng;WEI Xiaohui(Institute of Chinese Materia Medica,MOE Key Laboratory of Standardization of Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Guangxi Key Laboratory of Comprehensive Utilization Technology of Pseudo-ginseng,Wuzhou 543002,Guangxi,China;Guangxi Tianqi Personal Care Co.,Ltd,Wuzhou 543002,Guangxi,China)

机构地区：[1]上海中医药大学中药研究所,中药标准化教育部重点实验室,上海201203 [2]广西三七综合利用技术重点实验室,广西梧州543002 [3]广西田七家化实业有限公司,广西梧州543002

出　　处：《上海中医药大学学报》2024年第4期62-70,共9页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：广西科技计划项目“广西科技基地和人才专项”(桂科AD20297068);云南省三七生物技术与制药工程研究中心项目(E4-D2000402)。

摘　　要：目的:评价三七总皂苷(PNS)不同口服制剂对急性血瘀模型大鼠的药效差异,并与市售血栓通胶囊(XST)、三七通舒胶囊(SQTS)进行对比。方法:在前期研究基础上,分别制备PNS磷脂复合物肠溶胶囊(PNS-PC)、PNS pH依赖型固体分散体(PNS-SD)、PNS自乳化肠溶胶囊(PNS-SDEDDS)、PNS生物黏附微球肠溶胶囊(PNS-BMS)、N-乙酰-L半胱氨酸修饰的PNS生物黏附微球肠溶胶囊(PNS-NAC-BMS)5种不同PNS口服制剂。将80只SD大鼠随机分为对照(Control)组、模型(AD)组、XST+AD组、SQTS+AD组、PNS+AD组、PNS-PC+AD组、PNS-SD+AD组、PNS-SDEDDS+AD组、PNS-BMS+AD组、PNS-NAC-BMS+AD组,每组8只。给药组大鼠按照体质量及载药量给予相应剂量的药物灌胃,Control组、AD组大鼠给予空白胶囊灌胃。给药7 d后,采用注射盐酸肾上腺素加冰浴建立大鼠急性血瘀模型。次日,拍摄大鼠舌质及舌下脉络,评价舌象评分;尾静脉采血,记录尾静脉凝血时间;腹主动脉采血,检测血液流变学指标(包括不同切变率下的全血黏度、卡森黏度、血浆黏度)、凝血四项指标[包括活化部分凝血酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIB)]及血浆内皮素(ET)、内皮型一氧化氮合酶(eNOS)、6-酮前列腺素F1α(6-keto-PGF1α)含量。结果:①与Control组相比,AD组大鼠舌质发白、舌下血管紫黑,舌象评分显著升高(P<0.001),尾静脉凝血时间缩短(P<0.001),不同切变率下全血黏度、卡森黏度、血浆黏度均升高(P<0.001),APTT、PT、TT均缩短(P<0.001),FIB、ET水平升高(P<0.001),eNOS、6-keto-PGF1α水平均降低(P<0.001)。②与AD组相比,各给药组舌象评分均显著降低(P<0.001,P<0.01);与XST+AD组、SQTS+AD组相比,PNSPC+AD组、PNS-SDEDDS+AD组、PNS-BMS+AD组、PNS-NAC-BMS+AD组舌象评分亦显著降低(P<0.05)。③与AD组相比,PNS-PC+AD组、PNS-SDEDDS+AD组、PNS-BMS+AD组、PNS-NAC-BMS+AD组、PNS+AD组、XST+AD组、SQTS+AD组的尾静脉凝血时间均�Objective:To evaluate the pharmacodynamic differences of various oral preparations of Panax Notoginseng Saponins(PNS)on acute blood stasis model rats,and to compare them with commercially available Xueshuantong Capsules(XST)and Sanqitongshu Capsules(SQTS).Methods:Based on the previous studies,five different oral preparations of PNS including PNS phospholipid complex enteric capsules(PNS-PC),PNS pH-dependent solid dispersions(PNS-SD),PNS self-double-emulsifying enteric capsules(PNS-SDEDDS),PNS bioadhesive microsphere enteric capsules(PNS-BMS),and N-acetyl-L cysteine modified PNS bioadhesive microsphere enteric capsules(PNS-NAC-BMS)were prepared.Eighty SD rats were randomly divided into the Control group,model(AD)group,XST+AD group,SQTS+AD group,PNS+AD group,PNS-PC+AD group,PNS-SD+AD group,PNS-SDEDDS+AD group,PNS-BMS+AD group,PNS-NAC-BMS+AD group,8 rats in each group.The rats in drug administration groups were given the appropriate dose of drug by gavage according to the body mass and drug loading capacity,and the rats in Control and AD groups were given blank capsule by gavage.After 7 d of drug administration,the acute blood stasis model was established in rat by injection of epinephrine hydrochloride combined with ice bath.On the following day,the tongue images and sublingual veins of the rats were photographed to evaluate the tongue condition scores;the tail vein blood was collected to record the tail vein coagulation time;the abdominal aorta blood was collected,and the levels of blood rheological indexes(including whole blood viscosity at different shear rates,Carson’s viscosity,plasma viscosity),four indexes of coagulation[including activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)],and plasma endothelin(ET),endothelial-type nitric oxide synthase(eNOS),6-keto-prostaglandin F1α(6-keto-PGF1α)were detected.Results:①Compared with the Control group,the rats in AD group had whitish tongue,purple-black sublingual blood vessels,higher tongue condition score(P<0.00

关 键 词：三七总皂苷 口服制剂 急性血瘀模型 大鼠 药效学 

分 类 号：R285.5[医药卫生—中药学]