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
- 收稿：2022-05-19，
  
  网络首发：2023-01-17，
  
  纸质出版：2023-03-30
- 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. DOI: 10.3969/j.issn.1006-2157.2023.03.012.
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. DOI：

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

Keywords

references

VIRANI SS , ALONSO A , APARICIO HJ , et al . Heart Disease and Stroke Statistics－2021 Update: A Report From the American Heart Association [J]. Circulation , 2021 , 143 ( 8 )： 254 － 743 .

王玲，李群．冠心病患者肠道菌群分布及其与尿酸代谢的关系分析 [J]. 现代消化及介入诊疗， 2012 , 17 ( 6 ): 327 － 330 .

黄莹，谭超超．急性心肌梗死患者肠道优势菌群分析 [J]. 中国微生态学杂志， 2014 , 26 ( 9 ): 1004 － 1008 .

FUJIMURA KE , SLUSHER NA , CABANA MD , et al . Role of the gut microbiota in defining human health [J]. Expert Rev Anti Infect Ther , 2010 , 8 ( 4 ) : 435 － 454 .

CHEN YF , YANG FL , LU HF , et al . Characterization of fecal microbial communities in patients with liver cirrhosis [J]. Hepatology , 2011 , 54 ( 2 ): 562 － 572 .

ARUTYUNOV GP , KOSTYUKEVICH OI , SEROV RA , et al . Collagen accumulation and dysfunctional mucosal barrier of the small intestine in patients with chronic heart failure [J]. Int J Cardiol , 2007 ， 125 ( 2 )： 240 － 245 .

陈雪．注射用益气复脉(冻干)在正常大鼠和慢性心衰大鼠体内的药代动力学对比研究 [D]. 长春：吉林大学， 2018 .

何洋．芪参颗粒治疗慢性心衰大鼠的药代动力学研究 [D]. 长春：吉林大学， 2020 .

闫坤涛． ST段抬高型心肌梗死和不稳定性心绞痛患者肠道微生态和氧化三甲胺的临床研究 [D]. 天津：天津医科大学， 2018 .

LAM V , SU JD , KOPROWSKI S , et al . Intestinal microbiota determine severity of myocardial infarction in rats [J]. FASEB J , 2012 , 26 ( 11 ) ： 1727 － 1735 .

林王欧，郭书文，吴佳妮，等．益气活血药对心肌梗死后大鼠小肠黏膜屏障及肠道菌群的影响 [J]. 环球中医药， 2019 ， 12 ( 6 )： 824 － 830 .

萨础拉，吕航，姜艳艳，等．三七皂苷在大鼠外翻肠囊中的吸收及与P－糖蛋白相互作用研究 [J]. 北京中医药大学学报， 2011 ， 34 ( 12 )： 836 － 842 .

吴林霖，王爱民，李勇军，等．基于大鼠离体外翻肠囊模型考察杜仲提取物在正常和自发性高血压状态下的肠吸收特性差异 [J]. 中国实验方剂学杂志， 2018 , 24 ( 9 ): 15 － 21 .

ZHANG YQ , LU H , JIANG YF , et al . hAECs and their exosomes improve cardiac function after acute myocardial infarction in rats [J]. Aging , 2021 , 13 ( 11 ): 15032 － 15043 .

MENG H , ZHANG Y , AN ST , et al . Annexin A3 gene silencing promotes myocardial cell repair through activation of the PI3K/Akt signaling pathway in rats with acute myocardial infarction [J]. J Cell Physiol , 2019 , 234 ( 7 )： 10535 － 10546 .

WANG D , TIAN LY , LYU H , et al . Chlorogenic acid prevents acute myocardial infarction in rats by reducing inflammatory damage and oxidative stress [J]. Biomed Pharmacother , 2020 ， 132 ( 110773 )： 1 － 8 .

刘洋，张鑫，石秀佳，等．基于PBPK模型的在体单向肠灌流技术对苷元成分的适用性分析评价 [J]. 中国中药杂志， 2019 ， 44 ( 17 )： 3645 － 3652 .

LI HW , DONG L , LIU Y , et，al . Biopharmaceutics classification of puerarin and comparison of perfusion approaches in rats [J]. Inter J Pharm ， 2014 , 466 ( 1－2 )： 133 － 138 .

LIU Y , SUN J , ZHONG LY , et al . Combination of a biopharmaceutic classification system and physiologically based pharmacokinetic models to predict absorption properties of baicalein in vitro and in vivo [J]. J Trad Chin Med Sci , 2021 , 8 ( 3 )： 238 － 247 .

卢小芳．心肌梗死后大鼠胃肠功能紊乱发病机制及通心络的防治作用 [D]. 石家庄：河北医科大学， 2014 .

NIELSEN C , MORTENSEN F , ERLANDSEN E , et al . L and D-lactate as biomarkers of arterial-induced intestinal ischemia: an experimental study in pigs [J]. Int J Surg , 2012 , 10 ( 6 ): 296 － 300 .

黎介寿．加强对肠屏障功能障碍的研究 [J]. 中国临床营养杂志， 2003 ， 11 ( 4 ): 243 － 245 .

DERIKX J , MATTHIJSEN R , BRU N , et al . A new model to study intestinal ischemia-reperfusion damage in man [J]. J Surg Res , 2011 , 166 ( 2 ): 222 － 226 .

SANDEK A , BJARNASON I , VOLK H , et al . Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure [J]. Int J Cardiol , 2012 , 157 ( 1 ): 80 － 85 .

SANDEK A , BAUDITZ J , SWIDSINSKI A , et al . Altered intestinal function in patients with chronic heart failure [J]. J Am Coll Cardiol , 2007 , 50 ( 16 ): 1561 － 1569 .

SENTHONG V , LI X , HUDEC T , et al . Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with atherosclerotic burden [J]. J Am Coll Cardiol , 2016 , 67 ( 22 ): 2620 － 2628 .

EWASCHUK J , NAYLOR J , ZELLO G . D-lactate in human and ruminant-metabolism [J]. J Nutr , 2005 , 135 ( 7 ): 1619 － 1625 .

MAO Y , WANG SQ , MAO XB , et al . Intestinal barrier function in patients with acute myocardial infarction and the therapeutic effect of glutamine [J]. Inter J Cardiol , 2011 , 146 ( 3 ): 432 － 433 .

DONG ZX , LIANG ZG , GUO MH , et al . The association between plasma levels of trimethylamine N-oxide and the risk of coronary heart disease in Chinese Patients with or without Type 2 diabetes mellitus [J/OL]. Dis Mark , 2018 ： 1578320 . https：//www.hindawi.com/journals/dm/2018/15783201 https：//www.hindawi.com/journals/dm/2018/15783201 .

ZAKERI-MILANI P , BARZEGAR-JALALI M , AZIMI M , et al . Biopharmaceutical classification of drugs using intrinsic dissolution rate (IDR) and rat intestinal permeability [J]. Eur J Pharm Biopharm , 2009 , 73 ( 1 )： 102 － 106 .

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