目的 以成骨细胞增殖和分化为指标,通过正交模拟法与非线性混合效应模型(NONMEM)(DAS3.0软件)分析护骨胶囊(HG)各味药对药效的协同和拮抗作用,并对该方不同组合的复方进行药效模拟.方法 将HG 10个组分按照设计的正交表分为13个组,血清药理学实验获取13个组的含药血清,CCK-8法及AKP法检测各组血清对成骨细胞(Ob)增殖和分化的影响.DAS3.0软件处理数据,分析各味药对药效的协同和拮抗作用,并对复方药效进行模拟.结果 (1)以Ob分化为指标,淫羊藿、山药、巴戟天、熟地黄、杜仲对成骨细胞分化有促进作用,骨碎补、制首乌无作用,龟甲、当归、续断对Ob分化有抑制作用；以Ob增殖为指标,淫羊藿、骨碎补、巴戟天、山药、龟甲、当归、熟地黄、续断对Ob增殖有促进作用,杜仲及制首乌对ob增殖无作用.(2)以两种指标进行观察,DAS3.0软件处理不同组合的复方进行药效模拟发现,分化药效预测最大值为0.2263,且共有6个组分化药效预测值大于0.2,原方排第二；增殖药效预测值最大为1.1620,为原方,另外还有4个组增殖药效大于1.0；此外,将两个结果综合发现,有三个模拟组方同时满足分化大于0.2和增殖大于1.0.结论 利用Ob增殖和分化为指标,结合定量药理学方法综合分析HG,可提供丰富的组方信息,为HG的研究和开发提供了理论基础.%Objective With proliferation and differentiation of Osteoblasls as the indeχ, The orthogonal simulation method and NONMEM method were used to Study the efficacy of the Hugu capsule and Analysis of various herbs on the efficacy of synergism and antagonism. Method HC 10 components were divided into 13 groups,the drug serum of 13 groups were gotten by the serum pharmacological experiments, the method of AKP and CCK-8 were adopted to detect proliferation and differentiation of osteoblast and pharmacodynamic simulation of compound were analysis by DAS3. 0 software. Result the differentiation of Ob as a index, the effect were promoted by epimedium, yam, Morinda officinalis, prepared rehmanma root and Eucommia ulmotdes. Drynaria and Polygonum multiflorum were non-pharmacodynamic. The effect was inhibited by Turtleback, angelica and Himalayan Teasel Root. The proliferation of Ob as a index, the effect was promoted by epimedium, drynaria, Morinda officinalis, yam, turtleback, angelica, prepared rehmannia root and Himalayan Teasel Root. Eucommia ulmoides and Polygonum multifiorum were non-pharmacodynamic. (2) With proliferation and differentiation of Osteoblasts as the index, and date were analysised by DAS3. 0 software. The results of pharmacodynaniics of simulation compositions showed 6 groups differentiation efficacy predictive value greater than 0. 2, the maximum value of efficacy predicted is 0. 2263, the HG was the second. 5 groups proliferation efficacy predictive value greater than 1.0,the HC was the first,and value of efficacy predicted is 1. 1620; In addition, there are three simulation group meet to differentiation is greater than 0.2 and the proliferation of greater than 1.0. Conclusion Quantitative pharmacology methods were analysis of HC with proliferation and differentiation of Osteoblasts as the index, The method can provide rich formula information for HG,and provide a theoretical basis for research and development of the HC.
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