Kinetic Analysis of Enzymatic Reaction of Active Components from Xinshao Formula in Liver Microsomes of Sham-Operated and Cerebral Ischemia-reperfusion Injury Rats

Zhi-bao LIU; Dan WU; Juan TANG; Hong SU; Yue-ting LI; Zi-peng GONG; Yong HUANG; Yong-lin WANG

doi:10.13422/j.cnki.syfjx.20182305

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Kinetic Analysis of Enzymatic Reaction of Active Components from Xinshao Formula in Liver Microsomes of Sham-Operated and Cerebral Ischemia-reperfusion Injury Rats

Drug Metabolism | 更新时间：2021-02-09

- Kinetic Analysis of Enzymatic Reaction of Active Components from Xinshao Formula in Liver Microsomes of Sham-Operated and Cerebral Ischemia-reperfusion Injury Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 1, Pages: 169-176(2019)
- 作者机构：
  
  1.大庆油田总医院，黑龙江　大庆　 163312
  2.贵州医科大学　贵州省药物制剂重点实验室，药学院，药用植物功效与利用国家重点实验室，贵阳　 550004
  3.大庆医学高等专科学校，黑龙江　大庆　 163312
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20182305
  CLC： R22;R969.1;R945;R28;O657
- Received：29 May 2018，
  
  Published Online：19 September 2018，
  
  Published：05 January 2019
- 稿件说明：
移动端阅览
Zhi-bao LIU, Dan WU, Juan TANG, et al. Kinetic Analysis of Enzymatic Reaction of Active Components from Xinshao Formula in Liver Microsomes of Sham-Operated and Cerebral Ischemia-reperfusion Injury Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(1): 169-176.
DOI：

Zhi-bao LIU, Dan WU, Juan TANG, et al. Kinetic Analysis of Enzymatic Reaction of Active Components from Xinshao Formula in Liver Microsomes of Sham-Operated and Cerebral Ischemia-reperfusion Injury Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(1): 169-176. DOI： 10.13422/j.cnki.syfjx.20182305.

摘要

目的：

研究辛芍组方中效应成分灯盏乙素、灯盏甲素和芍药苷在正常大鼠和大脑中动脉闭塞（MCAO）局灶性脑缺血再灌注损伤大鼠肝微粒体中的酶促反应动力学，比较上述成分在不同状态大鼠肝微粒体中的体外酶代谢动力学差异。

方法：

制备不同状态大鼠的肝微粒体，将辛芍组方与大鼠肝微粒体进行孵育，选择UPLC-MS为分析手段，采用底物消除法，计算各成分在正常大鼠和MCAO大鼠肝微粒体中的酶反应动力学米氏常数（

），最大反应速率（

max

）及体外肝微粒体对药物的固有清除率（CL

int

），将各参数进行组间统计学分析。

结果：

灯盏乙素、灯盏甲素和芍药苷在正常大鼠体外肝微粒体中的

[（0.597±0.065），（0.166±0.012），（0.640±0.046） μmol·L

－1

]与MCAO大鼠中的

[（0.798±0.031），（0.213±0.017），（0.499±0.029） μmol·L

－1

]均明显不同；与正常组相比，MCAO大鼠体内的灯盏乙素和芍药苷的

max

和CL

int

均明显减少（

0.05，

0.01），灯盏甲素的

max

也显著降低（

0.05）。

结论：

辛芍组方的效应成分在脑缺血再灌注损伤大鼠肝微粒体中的代谢速率降低、消除减慢。

Abstract

Objective:

To investigate and compare enzymatic kinetics of scutellarin

apigenin-7-

-glucronide and paeoniflorin from Xinshao fomula in liver microsomes of sham-operated rats and middle cerebral artery occlusion(MCAO) rats with focal cerebral ischemia-reperfusion injury.

Method:

Xinshao fomula were incubated respectively with liver microsomes of sham-operated rats and MCAO rats

UPLC-MS and substrate elimination method was employed

Michaelis constant(

)

maximum velocity of enzymatic reaction(

max

) and intrinsic clearance(CL

int

) of these three components from Xinshao fomula in liver microsomes of sham-operated rats and MCAO rats were calculated

these parameters between different groups were evaluated by statistical analysis.

Result:

The

values of scutellarin

apigenin-7-

-glucronide and paeoniflorin in liver microsomes of MCAO rats were (0.798±0.031)

(0.213±0.017)

(0.499±0.029) μmol·L

-1

which were quite different to these in liver microsomes of sham-operated rats.Compared with the sham-operated group

max

and CL

int

values of scutellarin and paeoniflorin in liver microsomes of MCAO rats were significantly reduced(

0.05

0.01)

and

max

of apigenin-7-

-glucronide in liver microsomes of MCAO rat was also significantly reduced(

0.05).

Conclusion:

Metabolic rates of these three active components from Xinshao fomula in liver microsomes of MCAO rats with focal cerebral ischemia-reperfusion injury decrease with low elimination rate.

关键词

Keywords

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