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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: To conduct an exploratory and pharmacokinetic exploratory study based on microdialysis sampling with “real-time, in vivo, dynamic and minimally invasive” characteristics. Methods: Sprague-Dawley (SD) rats were given high-fat diet for 7 consecutive weeks and ligation of left anterior descending coronary artery. Normal group and phlegm and blood stasis type coronary heart disease group, Danshensu high and low dose group, 6 rats in each group, the dosage of Danshensu in the extract were 25.3,50.6 mg · kg-1, respectively Syndrome Differentiation and Pharmacokinetics in Normal and Coronary Heart Disease Rats. After a single intragastric administration, the concentrations of danshensu in the microdialysis samples were determined by in vivo micro-dialysis, dynamic sampling and HPLC, and pharmacokinetic parameters were obtained by non-compartmental model treatment. Results: The levels of total cholesterol (TC), triglyceride (TG) and serum creatine phosphokinase (CK) in the model group were increased. The viscosity of whole blood increased at high, middle and low shear rates. Compared with the normal group With statistical significance (P <0.01). The pharmacokinetic characteristics of Danshensu were obtained under different states of function. Compared with the normal group, the peak concentration of Danshensu (Cmax) in rats with phlegm and blood stasis type coronary heart disease increased, but there was no statistical significance; the peak time (Tmax) shortened, the AUC, The area under the curve (AUMC) increased compared with the normal group, the results were statistically significant (P <0.05). Conclusion: This study model can be used for reference for similar pharmacokinetic studies.