首页|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

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

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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,PNS-PC+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明显延长(P<0.001,P<0.01,P<0.05);与XST+AD组、SQTS+AD组相比,PNS-PC+AD组、PNS-SDEDDS+AD组、PNS-BMS+AD组、PNS-NAC-BMS+AD组大鼠尾静脉凝血时间亦明显延长(P<0.05).④与AD组相比,5种PNS自制口服制剂组大鼠的全血黏度、卡森黏度、血浆黏度水平均显著降低(P<0.001,P<0.01),XST+AD组、SQTS+AD组、PNS+AD组大鼠的全血黏度,XST+AD组的卡森黏度及PNS+AD组的血浆黏度水平亦降低(P<0.01,P<0.05);与XST+AD组、SQTS+AD组相比,PNS-PC+AD组大鼠的全血黏度水平亦降低(P<0.05);与SQTS+AD 组相比,PNS-PC+AD 组、PNS-BMS+AD 组、PNS-NAC-BMS+AD 组的卡森黏度水平降低(P<0.05).⑤与 AD组相比,各给药组大鼠的APTT、TT均明显延长(P<0.001,P<0.01,P<0.05),FIB水平均显著降低(P<0.01),PNS-PC+AD 组、PNS-SDEDDS+AD 组、PNS-BMS+AD 组、PNS-NAC-BMS+AD 组的 PT 亦显著延长(P<0.001,P<0.01);与 XST+AD 组、SQTS+AD 组相比,PNS-PC+AD 组、PNS-SDEDDS+AD 组、PNS-BMS+AD 组、PNS-NAC-BMS+AD 组 PT、TT 明显延长(P<0.05),FIB水平显著降低(P<0.01).⑥与AD组相比,各给药组大鼠的ET水平显著降低(P<0.001,P<0.05),eNOS、6-keto-PGF1α 水平显著升高(P<0.001,P<0.01,P<0.05);与 XST+AD 组、SQTS+AD 组相比,PNS-PC+AD组、PNS-SDEDDS+AD 组、PNS-BMS+AD 组、PNS-NAC-BMS+AD 组的 ET 水平显著降低(P<0.01),eNOS 水平显著升高(P<0.05),PNS-PC+AD 组、PNS-SD+AD 组、PNS-SDEDDS+AD 组、PNS-BMS+AD 组、PNS-NAC-BMS+AD 组的6-keto-PGF1α水平显著升高(P<0.01).结论:5种不同的PNS 口服制剂与原料药及市售XST、SQTS均能有效改善急性血瘀模型大鼠的瘀血状态,但PNS-PC、PNS-SDEDDS、PNS-BMS、PNS-NAC-BMS对血瘀大鼠各项血瘀相关指标的改善优于2种市售阳性药和原料药,具有较好的应用前景.
Pharmacodynamic comparison of Panax Notoginseng Saponins with different oral preparations on acute blood stasis model rats
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<0.001),shorter tail vein coagulation time(P<0.001),higher levels of whole blood viscosity at different shear rates,Carson's viscosity,and plasma viscosity(P<0.001),shorter APTT,PT,and TT(P<0.001),higher levels of FIB and ET(P<0.001),and lower levels of eNOS and 6-keto-PGF1α(P<0.001).②Compared with the AD group,the tongue condition scores of all administration groups were significantly decreased(P<0.001,P<0.01).Compared with the XST+AD group and the SQTS+AD group,the tongue condition scores of the PNS-PC+AD group,PNS-SDEDDS+AD group,PNS-BMS+AD group and PNS-NAC-BMS+AD group were also significantly decreased(P<0.05).③Compared with the AD group,the tail vein coagulation time of the PNS-PC+AD group,PNS-SDEDDS+AD group,PNS-BMS+AD group,PNS-NAC-BMS+AD group,the PNS+AD group,XST+AD group and SQTS+AD group was obviously prolonged(P<0.001,P<0.01,P<0.05).Compared with the XST+AD group and SQTS+AD group,the tail vein coagulation time of the PNS-PC+AD group,PNS-SDEDDS+AD group,PNS-BMS+AD group,and PNS-NAC-BMS+AD group was also obviously prolonged(P<0.05).④Compared with the AD group,the levels of whole blood viscosity,Carson's viscosity and plasma viscosity in the five self-prepared PNS oral preparation groups were significantly decreased(P<0.001,P<0.01),and the levels of whole blood viscosity in the XST+AD group,SQTS+AD group and PNS+AD group,the Carson's viscosity in the XST+AD group,and the plasma viscosity in the PNS+AD group were also decreased(P<0.01,P<0.05).Compared with the XST+AD group and SQTS+AD group,the whole blood viscosity level of the PNS-PC+AD group was also decreased(P<0.05).Compared with the SQTS+AD group,the levels of Carson's viscosity in the PNS-PC+AD group,PNS-BMS+AD group and PNS-NAC-BMS+AD group were decreased(P<0.05).⑤Compared with the AD group,the APTT and TT were significantly prolonged(P<0.001,P<0.01,P<0.05),and the FIB levels were significantly reduced(P<0.01)in all administration groups,and the PT was also significantly prolonged in the PNS-PC+AD group,PNS-SDEDDS+AD group,PNS-BMS+AD group and PNS-NAC-BMS+AD group(P<0.001,P<0.01).Compared with the XST+AD group and SQTS+AD group,the PT and TT were significantly prolonged(P<0.05)and the levels of FIB were significantly decreased(P<0.01)in the PNS-PC+AD group,PNS-SDEDDS+AD group,PNS-BMS+AD group and PNS-NAC-BMS+AD group.⑥Compared with the AD group,the ET levels were significantly decreased(P<0.001,P<0.05)and the levels of eNOS and 6-keto-PGF1α were significantly increased(P<0.001,P<0.01,P<0.05)in all administration groups.Compared with the XST+AD group and the SQTS+AD group,the levels of ET were significantly decreased(P<0.01)and the levels of eNOS were significantly increased(P<0.05)in the PNS-PC+AD group,PNS-SDEDDS+AD group,PNS-BMS+AD group and PNS-NAC-BMS+AD group,the levels of 6-keto-PGF1α were significantly increased in the PNS-PC+AD group,PNS-SD+AD group,PNS-SDEDDS+AD group,PNS-BMS+AD group,and PNS-NAC-BMS+AD group(P<0.01).Conclusion:The five self-prepared PNS oral preparations,as well as the APIs and XST and SQTS can effectively improve the blood stasis status in rats of acute blood stasis model.While the PNS-PC,PNS-SDEDDS,PNS-BMS and PNS-NAC-BMS are superior to the commercially available two positive medicines and APIs for the improvement of the various indexes related to blood stasis in rats,which have a better prospect for application.

Panax Notoginseng Saponinsoral preparationmodel of acute blood stasisratspharmacodynamics

王朔、仇坤、周利梅、陈明、赖树生、梁峰、尉小慧

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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)

广西三七综合利用技术重点实验室(广西梧州 543002)

广西田七家化实业有限公司(广西 梧州 543002)

三七总皂苷 口服制剂 急性血瘀模型 大鼠 药效学

广西科技计划广西科技基地和人才专项云南省三七生物技术与制药工程研究中心项目

桂科 AD20297068E4-D2000402

2024

上海中医药大学学报
上海中医药大学,上海市中医药研究院

上海中医药大学学报

CSTPCD
影响因子:0.788
ISSN:1008-861X
年,卷(期):2024.38(4)
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