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机构地区:[1]南方医科大学珠江医院中医科,广州510282
出 处:《中国实验方剂学杂志》2014年第16期119-123,共5页Chinese Journal of Experimental Traditional Medical Formulae
基 金:国家自然科学基金项目(81302882)
摘 要:目的:进行基于"实时、活体、动态、微创"特征的微透析采样技术的证治药动学探索性研究。方法:SD大鼠通过连续7周给予高脂饲料并结扎冠状动脉左前降支复制痰瘀互结型冠心病模型。正常组和痰瘀互结型冠心病组、丹参素高、低剂量组,每组各6只大鼠,提取物中丹参素的给药量为分别为25.3,50.6 mg·kg-1,进行正常和冠心病大鼠的证治药动学研究。单次灌胃给药后,血液微透析法活体、动态采样,高效液相色谱法检测微透析样品丹参素的浓度,采用非房室模型处理获得药动学参数。结果:模型组大鼠血清总胆固醇(TC)、甘油三酯(TG)、血清肌酸磷酸激酶(CK)升高,高、中、低切变率下全血黏度升高,与正常组差异具有统计学意义(P<0.01)。获取了不同机能状态下丹参素的药动学特征。和正常组相比,痰瘀互结型冠心病大鼠丹参素达峰浓度(Cmax)增加,但无统计学意义;达峰时间(Tmax)缩短,零阶矩(AUC)、一阶矩曲线下面积(AUMC)增加,和正常组相比,结果具有统计学意义(P<0.05)。结论:本研究模式可为类似证治药动学研究做借鉴。Objective:The syndrome and treatment pharmacokinetics model was carried out based on the ‘real-time,dynamic,minimally invasive,in vivo’ microdialysis sampling method.Method:The intermin-gled phlegm and blood stasis syndrome coronary heart disease SD rats model was replicated by feeding with high fat diet for 7 weeks combined with left anterior descending branch coronary artery ligation.The normal group and the model group were was divided into high and low dose group with 6 rats in each group,the extract of Danshensu dosage was respectively 25.3,50.6 mg · kg-1.The pharmacokinetics study was carried out on normal and coronarg heatt disease (CHD) rats by intragastric administration of different dose.The Danshensu concentration of microdialysis samples were detected with HPLC and the pharmacokinetic parameters was obtained using noncompartmental model.Result:The results showed that serum total cholesterol (TC),triglyceride (TG),creatine phosphokinase (CK) in the model group increased,blood viscosity of high,medium and low shear also increased.The results had highly statistically significant differences compared with the normal group (P < 0.01).The results showed that Danshensu peak concentration increases,but without statistical significance,the peak time shorten,area under the curve (AUC) and area under the first moment curve (AUMC) increases in CHD rats comparing with the normal group,the results were statistically significant (P < 0.05).Conclusion:This study can be the reference for the similar research mode.
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