基于权重配方法的复方大黄素黄芩素治疗重症急性胰腺炎的组分配伍优化研究

Dosage Optimization of Compound Emodin-Baicalein on Severe Acute Pancreatitis on the Basis of Weighted Modifidion Method

目的探讨复方大黄素黄芩素组分配比的最优方案。方法健康雄性Sprague Dawley大鼠,随机分成正常组、假手术组、重症急性胰腺炎(SAP)组及治疗组。SAP组及治疗组模型制备均采用5%牛磺胆酸钠逆行胰胆管注射法。各组观察至12h分别处死取材,检测胰腺组织病理学评分和血清α-淀粉酶活性;筛选大黄素和黄芩素治疗SAP的有效剂量范围;研究大黄素、黄芩素联用治疗SAP的最佳剂量、配比和复方大黄素黄芩素量效关系。结果与正常组比较,SAP组病理学评分和α-淀粉酶活性均明显升高(P<0.05)。与SAP组比较,各配比治疗组病理学评分和α-淀粉酶活性均明显下降(P<0.05)。配比一组(大黄素3.24mg/kg+黄芩素7.12mg/kg)病理学评分下降最为明显,且优于二、三、四、五、六配比组(P<0.05)。配比一组α-淀粉酶活性明显优于二、四配比组(P<0.05),三、五、六配比组比较,差异无统计学意义(P>0.05)。经大型药理学软件DAS分析,组方中大黄素的标化剂量为0.126,黄芩素的标化剂量为0.107。结论复方大黄素黄芩素的最优组方剂量为大黄素3.24mg/kg和黄芩素7.12mg/kg,最佳配比为1∶2.2。

Objective To investigate the dosage optimization of compound emodin-baicalein. Methods Male Sprague Dawley rats were randomly divided into the normal group, the sham operation group, the severe acute pancreatitis （SAP） group, and the treatment group, the rats in SAP group and treatment group were induced by retrograde injection of 5% sodium taurocholate into the common biliopan- creatic duct. All the rats were sacrificed at 12 h after model preparation. The histopathology scores of pan- creas and serum amylase activity were determined 12 h after the surgery to screen the dosage of emodin and baicalein in SAP, to optimize the dosage of combination of emodin and baicalein and to study the dose- effect relationship of combination of emodin and baicalein. Results Compared with the normal group, the histopathology scores and serum amylase activity increased in SAP group （P 〈0.05）. Compared with the SAP group, the markers decreased in 6 treatment groups （P 〈0.05）. Compared with other 5 treatmentgroups, the histopathology score decreased in ratio 1 group （emodin 3.24 mg/kg ＋ baicalein 7.12 mg/kg, P 〈0.05）. Compared with the ratio 2 and ratio 4 group, the serum amylase activity decreased in ratio 1 group （P 〈0.05）. Nevertheless, compared with the ratio 1 group, the serum amylase activity showed no statistic difference in ratio 3, ratio 5 and ratio 6 group （P 〉0.05）. Emodin showed a principal role in the compound recipe, whereas baicalein served as adjuvant ingredient by DAS software analysis. Conclusions The optimal combination of emodin and baicalein is with dose of emodin 3.24 mg/kg and baicalein 7.12 mg/kg and the optimal ratio of emodin and baicalein is 1：2.2.