August 26 Vol.8 No carmichaeli cinnamon dried rehmannia yam dogwood moutan bark rhizoma alismatis poria cocos be The regul

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1 August 26 Vol.8 No mg/ kg d d 2 d ACTH COR ACTH COR.5 g.56 g.28 g.2 g R285.5 A DOI.357/j.cnki.jncm Component Optimization Study of Shenqi Wan Based on Response Surface Analysis WANG Yumei GAO Jie LI Zhengmu ZHANG Xuqian CHEN Nandi CHEN Gongcheng ZHANG Yumin JIANG Shuxia Abstract 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 9 groups randomly cases in each group. Designed scheme as per response surface set 7 groups as Chinese medicine (CM) group other two groups set as blank group and model group. All the mice were fed adaptive for 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 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 2 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.5g respectively dried rehmannia was.56 g yam and dogwood were.28 g respectively moutan bark rhizoma alismatis and poria cocos were.2g 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 lzm@gzucm.edu.cn

2 August 26 Vol.8 No carmichaeli cinnamon dried rehmannia yam dogwood moutan bark rhizoma alismatis poria cocos be The regulating effect of above prescription on adrenal cortex hypofunction are more significant effect on warming and invigorating kidney yang are optimal. Keywords Shenqi wan Response surface analysis Component optimization Kidney- yang deficiency model Animal experiment Mice ( ) ( ) - ( ) ( ) ( ) ( ) ( ( + )/g X.8..3 ) ( ) ( + + )/g X 2 ( + + )/g X mg/(kg.d) [] d ( (ACTH) (COR) [2] ) 2 d ml 9 h min r/min 592 scxk( ) ±2 g Design Expert V.8..5b ( ) 3 ( 3. H285) ( H22887).3 [3] (ACTH)ELISA ( RB Rapidbio ) (COR)ELISA ( 3.2 (ELISA) RB Rapidbio ). AEG- 22 ( ) CR22G PerkinElmer X5 ( PE ) Biotek Elx5 ( Biotek. 5 ) DT5-3 ( ) 2 2. ( + )X ( + + )X 2 ( + (ACTH) (COR) ELISA 2 + )X 3 (-).2 3 () () (ACTH) (COR) (Y) Box- Benhnken.3 Design Expert 3 ACTH

3 August 26 Vol.8 No COR 5 (g) (g) ACTH 8.22±.7 29.±3.69 F >F Suggest ed ± ±5.27 VS ±. 25.9±3.95 VS ±. 32.6±.7 VS Suggest ed 5 7.6± ±3.95 VS Aliased ± ±3.36 VS ± ± ±. 28.3± ± ± ± ±2.2 5 COR 7.2± ±2.8 F >F ± ±2.72 VS Suggest ed ± ± ± ±2.85 VS 2.3 VS ±. 25.8±.98 VS Suggest ed 6 8.2±.2 32.±2.8 VS Aliased 7 7.2± ± ± ± ± ± ACTH (X) (Y) ( + ) ( + ( + (ACTH)pg/mL (COR)ng/mL /g X + )/g X 2 + )/g X Y= X X X X X X X X 2 X X X X 3 Y (ACTH) X X 2 X 3 ( + )X ( + + ) X 2 ( + + )X 3 (ACTH) - 6 y=f (X X 2 ) (X 3 =)

4 新中医 26 年 8 月第 8 卷第 8 期 图2 August 26 Vol.8 No.8 y=f (X X2) 的响应面图 (X3=) 图6 295 y=f (X2 X3) 的响应面图 (X=) 通过模型分析 建立 COR 的多元二次响应面回归模型 得拟合方程 Y= X X X X X XX X2X X X X32 其中 Y 是效应值皮质醇(COR)含量 X X2 和 X3 为自变 量 即(肉桂 + 附子)X (干地黄 + 山药 + 山茱萸)X2 和(牡丹皮 + 泽泻 + 茯苓)X3各因素与指标之间不是简单的线性关系 而是二次关系经分析计算后可知 小鼠肾气丸最佳使用剂量 图3 y=f (X X3) 的等高线图 (X2=) X 为.256 g X2 为.35 g X3 为.6 g在此条件下 取 得 的 小 鼠 血 清 ACTH 含 量 为 pg/m L COR 含 量 为.529 pg/m L考虑到实际应用及方差分析结果 确定小鼠 肾气丸最佳使用剂量为 肉桂 附子各.5 g 干地黄.56 g 山药 山茱萸各.28 g 牡丹皮 泽泻 茯苓各.2 g 并按此条件进行验证实验 测得小鼠血清 ACTH 含量为 2.2 pg/m L COR 含量为 3.63 pg/m L根据实验结果 并结合临 床实际应用情况 以及普通高等教育中医药类规划教材 方剂 学 书本记载 肉桂 附子各 3 g 干地黄 2 g 山药 山茱 萸各 2g 牡丹皮 泽泻 茯苓各 9 g 推断若将肾气丸组方 中肉桂和附子剂量增加 倍 干地黄 山药 山茱萸保持不 图 y=f (X X3) 的响应面图 (X2=) 变 牡丹皮 泽泻 茯苓亦增加 倍 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 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 讨论 本实验对肾气丸进行组方优化研究旨在优化组方的剂量及 配比 不改变药物组成实验运用糖皮质激素氢化可的松建立 小鼠肾阳虚模型 根据肾气丸不同剂量配比对肾阳虚小鼠临床 症状 血清 ACTH 和 COR 含量的改善情况 来寻找肾气丸温 补肾阳作用的最佳配比剂量研究结果发现 肉桂和附子剂量 增加 倍 干地黄 山药 山茱萸保持不变 牡丹皮 泽泻 茯苓亦增加 倍 即附子 肉桂 干地黄 山药 山茱萸 图5 y=f (X2 X3) 的等高线图 (X=) 牡丹皮 泽泻 茯苓的比例为 其

5 August 26 Vol.8 No.8 []. HPA [J] (7) 5-7. [2]. [M] [3]. [J]. 986(2) D 5 6 E 2 P HE E 2 P P <. E 2 P R285.5 A DOI.357/j.cnki.jncm (endometrial receptivity ER) (assisted reproductive techniques ART) RJZA