基于响应面分析法的肾气丸组方优化研究

Component Optimization Study of Shenqi Wan Based on Response Surface Analysis

目的:优化肾气丸组方的最佳剂量配比,为临床有效地运用肾气丸防治疾病提供可靠依据。方法:将昆明种小鼠随机分为19组,每组10只。按响应面设计方案,其中17组为中药组,其余2组为空白组及模型组。小鼠在适应性喂养1周后,除空白组小鼠外,其余组小鼠均每天腹腔注射氢化可的松注射液25 mg/(kg·d)制造肾阳虚小鼠模型,连续10 d。同时中药组灌胃给予肾气丸中药水煎液,空白组、模型组给予等体积生理盐水,连续给药20 d。观察各组小鼠肾阳虚临床症状变化情况,以及血清中促肾上腺皮质激素(ACTH)、皮质醇(COR)的含量变化。结果:模型组与各中药治疗组比较,自主活动明显减少,畏寒显著,多尿症状明显,且血清ACTH和COR含量显著低下。通过优化并进行验证实验,小鼠肾气丸最佳使用剂量为肉桂、附子各0.15 g,干地黄0.56 g,山药、山茱萸各0.28 g,牡丹皮、泽泻、茯苓各0.42 g。结论:肾气丸原方剂量相对偏低,若将肾气丸组方中肉桂、附子、牡丹皮、泽泻、茯苓剂量增加1倍,干地黄、山药、山茱萸保持不变,即肾气丸中各药物配伍比例调整为:附子∶肉桂∶干地黄∶山药∶山茱萸∶牡丹皮∶泽泻∶茯苓为2∶2∶8∶4∶4∶6∶6∶6,其对肾上腺皮质功能低下的调节作用更加显著,温补肾阳作用最佳。

Objective：To optimize optimum dose matching of Shenqi wan component,and provide reliable evidence for preventing and treating disease with Shenqi pill clinically.Methods：Divided Kunmin mouse into 19 groups randomly,10 cases in each group.Designed scheme as per response surface,set 17 groups as Chinese medicine（CM） group,other two groups set as blank group and model group.All the mice were fed adaptive for 1 week.Except mice in blank group,mice in all of the other group were injected hydrocortisone 25 mg/（kg·d） intraperitoneally to make kidney-yang deficiency model for 10 consecutive days.At the same time,CM groups were gavaged Shenqi wan,blank group and model group were given isovolumetric normal saline,successive medication for 20 days.Observed changes of kidney-yang deficiency clinical symptom,and content changes of adrenocorticotrophic hormone（ACTH）,cortisol（COR） in serum.Results：Comparing with CM group,locomotor activity in model group was decreased obviously,intolerance of cold and polyuria symptom was obvious,and contents of ACTH and COR in serum were decreased significantly.By optimization and verify experiment,Shenqi wan optimal dose as follows：cinnamon and radix aconiti carmichaeli were 0.15 g respectively,dried rehmannia was 0.56 g,yam and dogwood were 0.28 g respectively,moutan bark,rhizoma alismatis and poria cocos were 0.42 g respectively.Conclusion：The Shenqi wan dose in original prescription is low relatively.If contents of cinnamon,radix aconiti carmichaeli,moutan bark,rhizoma alismatis and poria cocos are double,content of dried rehmannia,yam and dogwood remain are unchanged,that is,drugs compatibility proportion in Shenqi wan is adjusted to the following：radix aconiti carmichaeli：cinnamon：dried rehmannia：yam：dogwood：moutan bark：rhizoma alismatis：poria cocos be 2：2：8：4：4：6：6：6.The regulating effect of above prescription on adrenal cortex hypofunction are more significant,effect on warming and invigorating kidney yang are optimal.