心肌梗死对芪参益气滴丸活性成分的肠吸收影响研究

刘洋; 孙晶; 孙静; 朱博; 朱雨欣; 李宇; 董玲

doi:10.3969/j.issn.1006-2157.2023.03.012

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心肌梗死对芪参益气滴丸活性成分的肠吸收影响研究

实验研究 | 更新时间：2023-04-07

- 心肌梗死对芪参益气滴丸活性成分的肠吸收影响研究
- Effect of myocardial infarction on the intestinal absorption of the active ingredients of Qishen Yiqi Dripping Pills
- 北京中医药大学学报 2023年46卷第3期页码：357-365
- 作者机构：
  
  北京中医药大学　北京　102488
- 作者简介：
  
  刘洋，女，博士
  #董玲，女，教授，研究员，博士生导师，主要研究方向：中药标准化、中药生物药剂学及中药制剂新技术，E-mail：dongling@bucm.edu.cn
- 基金信息：
  
  国家自然科学基金项目(81473362)
- DOI：10.3969/j.issn.1006-2157.2023.03.012
  中图分类号： R284
- 纸质出版日期：2023-03-30，
  
  网络出版日期：2023-01-17，
  
  收稿日期：2022-05-19，
- 稿件说明：
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刘洋, 孙晶, 孙静, 等. 心肌梗死对芪参益气滴丸活性成分的肠吸收影响研究[J]. 北京中医药大学学报, 2023,46(3):357-365.

LIU Yang, SUN Jing, SUN Jing, et al. Effect of myocardial infarction on the intestinal absorption of the active ingredients of Qishen Yiqi Dripping Pills[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023,46(3):357-365.
刘洋, 孙晶, 孙静, 等. 心肌梗死对芪参益气滴丸活性成分的肠吸收影响研究[J]. 北京中医药大学学报, 2023,46(3):357-365. DOI： 10.3969/j.issn.1006-2157.2023.03.012.

LIU Yang, SUN Jing, SUN Jing, et al. Effect of myocardial infarction on the intestinal absorption of the active ingredients of Qishen Yiqi Dripping Pills[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023,46(3):357-365. DOI： 10.3969/j.issn.1006-2157.2023.03.012.

摘要

目的

探讨心肌梗死对芪参益气滴丸活性成分的肠吸收影响。

方法

雄性SD大鼠25只。任意选取15只，采用结扎左冠状动脉前降支的方法构建心肌梗死模型，其余10只纳入正常组。术后7 d，通过对心电图、心肌组织切片、小肠组织切片及血清生物标志物5－羟色胺(5－HT)与内毒素(LPS)含量的检测，确定造模情况及肠道黏膜屏障生理状态。术后7～9 d，采用在体单向肠灌流技术进行芪参益气滴丸活性成分的肠吸收研究，灌流液终质量浓度均为30 g/L，经质量差法获得肠吸收相关参数(有效渗透系数、吸收速率常数及吸收分数)的数值与差异。

结果

模型组大鼠心电图显示6～8个Q波，ST段具有弓背向上抬高现象。与正常组比较，心肌组织和小肠组织的HE病理切片细胞形态学改变，较多炎性细胞浸润，血清5－HT和LPS含量升高(

0.05)；不同芪参益气滴丸活性成分的吸收速率和变化程度各不相同。其中，模型组丹参素、原儿茶醛、丹参酮ⅡA、毛蕊异黄酮、人参皂苷Rb1和反式－橙花叔醇跨肠膜吸收速率增加(

0.05)，人参皂苷Rb1和反式－橙花叔醇体内吸收程度同时提升(

0.05)；丹参素、毛蕊异黄酮由低渗透性转变为高渗透性；丹酚酸A、迷迭香酸、人参皂苷Rg1、三七皂苷R1和黄芪甲苷Ⅳ肠吸收相关参数变化差异无统计学意义(

0.05)。

结论

结扎左冠状动脉前降支可成功复制心肌梗死模型。心肌梗死模型大鼠心脏组织及小肠组织均有受损现象，心肌梗死导致了肠道黏膜屏障功能发生改变，对芪参益气滴丸不同活性成分的肠吸收影响是复杂且非特异的。

Abstract

Objective

We aimed to explore the effect of myocardial infarction (MI) on the intestinal absorption of the active ingredients of

Qishen Yiqi

Dripping Pills (QSYQ).

Methods

Twenty-five male Sprague-Dawley rats were used. Fifteen rats were randomly selected to establish the MI model by ligating the left anterior descending coronary artery; the remaining rats were used as the normal group. Seven-day postoperative MI model rats were taken to confirm the model was successfully established and to determine the physiological status of the intestinal mucosal barrier by electrocardiography (ECG)

by analyzing myocardial and intestinal tissue sections

and by measuring the levels of the serum biomarkers 5-hydroxytryptamine (5-HT) and lipopolysaccharides(LPS). In normal and seven to nine day postoperative MI model rats

the intestinal absorption of the active ingredients of QSYQ was studied by the single-pass intestinal perfusion method. The final concentration of perfusate was 30 g/L. Values and differences of parameters related to intestinal absorption such as the effective permeability coefficient

absorption rate constant

and absorption fraction were obtained by the weight difference method.

Results

The ECGs of MI model rats showed 6-8 Q waves and ST-segment elevation. Cytomorphological changes in HE-stained pathological sections of myocardial and intestinal tissues of rats were observed in the model group

with more inflammatory cell infiltration. The serum concentrations of 5-HT and LPS were higher in the model group (

0.05). The rate and extent of absorption of the different components varied in MI rats compared to normal rats. The trans-intestinal membrane absorption rates of danshensu

protocatechualdehyde

tanshinone IIA

calycosin

ginsenoside Rb1

and trans-nerolidol were higher in MI rats (

0.05)

and the in vivo absorption fractions of ginsenoside Rb1 and trans-nerolidol were also simultaneously increased (

0.05). Danshensu and calycosin changed from low to high permeability. There were no significant differences in parameters related to intestinal absorption of salvianolic acid A

rosmarinic acid

ginsenoside Rg1

notoginsenoside R1

and astragaloside Ⅳ in the disease state.

Conclusion

The MI rat model was established successfully after ligating the left anterior descending coronary artery. Morphological changes in myocardial and intestinal tissues of rats were observed. MI changed the mucosal barrier function of the intestine. The effects of the infarct state on the absorption of different types of components were complex and non-specific.

关键词

芪参益气滴丸心肌梗死在体单向肠灌流肠吸收渗透性大鼠

Keywords

Qishen Yiqi Dripping Pillsmyocardial infarctionthe single-pass intestinal perfusion methodintestinal absorptionpermeabilityrats

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