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纸质出版日期:2011
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成龙, 王岚, 王彦礼, 等. 金铃子散不同配比方对大鼠肝药酶CYP450 3A4活性的影响[J]. 中国实验方剂学杂志, 2011,17(22):117-122.
CHENG Long, WANG Lan, WANG Yan-li, et al. Influence of Jinglingzi Powder with Different Compatibility on the Activity of Cytochrome P450 3A4 from Rat Liver Microsomes[J]. Chinese journal of experimental traditional medical formulae, 2011, 17(22): 117-122.
成龙, 王岚, 王彦礼, 等. 金铃子散不同配比方对大鼠肝药酶CYP450 3A4活性的影响[J]. 中国实验方剂学杂志, 2011,17(22):117-122. DOI: CNKI:11-3495/R.20110920.1429.002.
CHENG Long, WANG Lan, WANG Yan-li, et al. Influence of Jinglingzi Powder with Different Compatibility on the Activity of Cytochrome P450 3A4 from Rat Liver Microsomes[J]. Chinese journal of experimental traditional medical formulae, 2011, 17(22): 117-122. DOI: CNKI:11-3495/R.20110920.1429.002.
目的: 通过比较金铃子散不同配比方对肝细胞色素P450 3A4(cytochrome P450 3A4
简称CYP 3A4)活性的影响
探讨其配伍规律。 方法: 按L9(34)正交表
设计9个不同配比组方。体外实验采用大鼠肝微粒体孵育体系
测定不同配比方对CYP 3A4的半数抑制浓度(IC50);体内实验采用大鼠
口服给予金铃子散不同配比方5 d后注射探针药物睾酮
通过微透析探针采集肝脏部位样品
HPLC测定6-β-羟基-睾酮和原型物睾酮浓度
二者浓度之比作为CYP 3A4酶活性指标。 结果: 川楝子、延胡索单味提取物和配比方1~9体外对肝药酶CYP 3A4的IC50分别为(2.59±0.33)
(0.87±0.30)
(1.14±0.20)
(1.00±0.13)
(1.19±0.10)
(2.33±0.15)
(1.39±0.19)
(1.14±0.20)
(1.29±0.14)
(1.43±0.32)
(1.49±0.28) mg·L-1;体内实验结果显示:与正常对照组比较
金铃子散不同配比方、川楝子和延胡索单味提取物处理组大鼠CYP 3A4的酶活性均降低
金铃子散配比方抑制CYP 3A4 酶活性的强弱顺序:方1(方4)>方7>方2(方5)>方8>方3>方9。 结论: 不同配比方对CYP 3A4酶的活性均有影响
川楝子和延胡索配伍显示出协同抑制作用。
Objective: To illustrate the compatibility of Jinglingizi powder by investigating the influence of Jinglingzi powder with different compatibility on the enzymatic activity of cytochrome P450 3A4(CYP 3A4) from rat liver microsome. Method: The different compatibility of Jinglingizi powder was designed based on the orthogonal array L9(34). In vitro test
rat liver microsome incubation system was applied to detect the 50% inhibitory concentration of Jinglingzi powder with different compatibility. In vivo experiment
rats were administered orally with the different compatibility of Jinglingizi powder (dose: 9.75 g·kg-1) from day 1 to day 5
then injected probe drug testosterone. The biosamples from liver tissue were obtained by microdialysis probe
then to be analysed by HPLC. The concentration of 6-β-testosterone and testosterone were accurately determined. The ratio hepatic concentration of 6-β-testosterone to hepatic concentration of testosterone
was applied to describe the CYP 3A4 enzyme activity. Result: The half maximal inhibitory concentrations (IC50) of the extract of Toosendan fruit
Rhizoma Corydalis and Jinlingzi Powder(formula.1-9) on the enzymatic activity of CYP3A4 were (2.59±0.33)
(0.87±0.30)
(1.14±0.20)
(1.00±0.13)
(1.19±0.10)
(2.33±0.15)
(1.39±0.19)
(1.14±0.20)
(1.29±0.14)
(1.43±0.32)
(1.49±0.28) mg·L-1
respectively. In vivo test
the CYP3A4 enzyme activity was inhibited by the different compatibility of Jinglingizi powder
compared with the normal control group. The inhibited intensity of Jinglingizi powde followed the order: formula 1 (formula 4)> formula 7 > formula 2(formula 5) > formula 8> formula 3> formula 9. Conclusion: The CYP3A4 enzyme activity is inhibited by the different compatibility of Jinglingizi powder
compared with the normal control group. Compatibility of Jinglingizi powder synergetically down-regulate the the CYP3A4 enzyme activity.
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