Comparative Study on Effect of <italic style="font-style: italic">Yiqi Liangxue Shengji Formula</italic> （益气凉血生肌方） and Atorvastatin Tablets on Vascular Injury and Differences in Serum Metabolites in Abdominal Aortic Balloon Injury Model Rats

MAO Tianshi; XIE Long; GAO Qun; PAN Yi; JIA Wenhao; LIN Qian

doi:10.13288/j.11-2166/r.2024.11.016

您当前的位置：

首页 >

文章列表页 >

Comparative Study on Effect of Yiqi Liangxue Shengji Formula （益气凉血生肌方） and Atorvastatin Tablets on Vascular Injury and Differences in Serum Metabolites in Abdominal Aortic Balloon Injury Model Rats

更新时间：2024-05-24

- Comparative Study on Effect of Yiqi Liangxue Shengji Formula （益气凉血生肌方） and Atorvastatin Tablets on Vascular Injury and Differences in Serum Metabolites in Abdominal Aortic Balloon Injury Model Rats
- Journal of Traditional Chinese Medicine Vol. 65, Issue 11, Pages: 1180-1188(2024)
- 作者机构：
  
  1.北京中医药大学东直门医院，北京市东城区海运仓5号，100700
  2.北京中医药大学第三附属医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2024.11.016
  CLC：
- Received：18 September 2023，
  
  Revised：2023-11-22，
  
  Published：02 June 2024
- 稿件说明：
移动端阅览
毛天诗,谢龙,高群等.益气凉血生肌方与阿托伐他汀片对腹主动脉球囊损伤模型大鼠血管损伤及血清代谢物差异的影响比较研究[J].中医杂志,2024,65(11):1180-1188.

MAO Tianshi,XIE Long,GAO Qun,et al.Comparative Study on Effect of Yiqi Liangxue Shengji Formula （益气凉血生肌方） and Atorvastatin Tablets on Vascular Injury and Differences in Serum Metabolites in Abdominal Aortic Balloon Injury Model Rats[J].Journal of Traditional Chinese Medicine,2024,65(11):1180-1188.
毛天诗,谢龙,高群等.益气凉血生肌方与阿托伐他汀片对腹主动脉球囊损伤模型大鼠血管损伤及血清代谢物差异的影响比较研究[J].中医杂志,2024,65(11):1180-1188. DOI： 10.13288/j.11-2166/r.2024.11.016.

MAO Tianshi,XIE Long,GAO Qun,et al.Comparative Study on Effect of Yiqi Liangxue Shengji Formula （益气凉血生肌方） and Atorvastatin Tablets on Vascular Injury and Differences in Serum Metabolites in Abdominal Aortic Balloon Injury Model Rats[J].Journal of Traditional Chinese Medicine,2024,65(11):1180-1188. DOI： 10.13288/j.11-2166/r.2024.11.016.

摘要

目的

从代谢组学角度对比分析益气凉血生肌方与阿托伐他汀对大鼠血管损伤修复的影响及可能机制。

方法

将24只SD大鼠随机分为假手术组、模型组、益气凉血生肌方组、阿托伐他汀组，每组6只。除假手术组外其余各组大鼠采用球囊拉伤腹主动脉构建血管损伤大鼠模型。各组大鼠术后当天开始灌胃，假手术组、模型组大鼠灌胃去离子水15 ml/（kg·d），益气凉血生肌方组予益气凉血生肌方混悬液6 g/（kg·d）灌胃，阿托伐他汀组予阿托伐他汀混悬液2 mg/（kg·d）灌胃。各组均连续灌胃4周后，HE染色观察腹主动脉损伤段病理形态；ELISA法检测血清一氧化氮（NO）及C反应蛋白（CRP）水平；采用超高效液相色谱-质谱联用（UPLC–MS/MS）技术进行血清广泛靶向代谢组学检测，运用多元统计分析方法筛选两种药物的代谢标志物及代谢途径；比较各组大鼠两种药物血清关键代谢标志物水平。

结果

与假手术组相比，模型组大鼠腹主动脉病理显示新生内膜明显增生，检测血清NO水平明显降低、CRP水平明显升高（

＜0.01）；与模型组相比，益气凉血生肌方组与阿托伐他汀组大鼠动脉内膜增生程度均减轻，血清NO水平升高、CRP水平下降（

＜0.05或

＜0.01）。血清代谢组学结果显示，益气凉血生肌方组获得49种代谢标志物、6条代谢途径，阿托伐他汀组获得41种代谢标志物、4条代谢途径。两种药物共同调节38种代谢物，甘油磷脂代谢和精氨酸相关代谢是两种药物的共同代谢途径，溶血磷

脂酰胆碱（16∶1/0∶0）［LPC（16∶1/0∶0）］、磷脂酰胆碱（15∶0/15∶0）［PC（15∶0/15∶0）］为甘油磷脂代谢途径的关键代谢物，鸟氨酸、亚精胺为精氨酸相关代谢途径的关键代谢物。三羧酸循环、谷胱甘肽代谢是益气凉血生肌方独有的代谢途径。与假手术组相比，模型组LPC（16∶1/0∶0）、鸟氨酸、亚精胺水平均升高，PC（15∶0/15∶0）水平下降（

＜0.05或

＜0.01）。与模型组相比，益气凉血生肌方组及阿托伐他汀组LPC（16∶1/0∶0）、鸟氨酸、亚精胺水平均降低，PC（15∶0/15∶0）水平升高（

＜0.05或

＜0.01）。与益气凉血生肌方组相比，阿托伐他汀组LPC（16∶1/0∶0）降低程度更为显著（

＜0.01）。

结论

益气凉血生肌方与阿托伐他汀均可调节脂质代谢及精氨酸相关代谢，发挥降血脂、抗炎、提高精氨酸/NO生物利用、改善内皮功能障碍的作用。阿托伐他汀在降脂、抗炎方面更具优势，而益气凉血生肌方在调节能量代谢、改善氧化应激方面更佳。

Abstract

Objective

To compare the effects and differences of

Yiqi Liangxue Shengji Formula

（益气凉血生肌方） and atorvastatin on the repair of vascular injury in rats from the perspective of metabolomics.

Methods

Twenty-four male SD rats were randomly divided into sham-surgery， model， traditional Chinese medicine （TCM）， and ator-vastatin groups， with 6 rats in each group. The rat model was established by balloon-induced abdominal aorta injury. Gavage was started on the day after surgery in all groups of rats. The sham and model groups were given with deio-nized water， TCM group received

Yiqi Liangxue Shengji Formula

6 g/（kg·d）， and the atorvastatin group treated with atorvastatin suspension 2 mg/（kg·d） for 4 weeks. HE staining was used to observe the pathological morphology of the injured segment of the abdominal aorta； ELISA detection was used to test serum nitric oxide （NO） and C-reactive protein （CRP） levels； UPLC MS/MS technology was used for widely targeted metabolomics detection in serum， and multivariate statistical analysis was used to screen metabolic markers and pathways of two drugs； finally， compare serum levels of key metabolic markers of the above two medications in rats of each group.

Results

Compared with the sham-surgery group， the neointima significantly thickened， the le

vel of NO decreased significantly and the level of CRP increased in serum of the model group （

＜0.01）； compared with the model group， the degree of arterial intimal hyperplasia in TCM group and atorvastatin group reduced， with an increase in NO levels and a decrease in CRP levels （

＜ 0.05 or

＜0.01）. The results of serum metabolomics showed that TCM group obtained 49 metabolic markers and 6 metabolic pathways， while atorvastatin group obtained 41 metabolic markers and 4 metabolic pathways. The two medications jointly regulated 38 metabolites. Glycerophospholipid metabolism and arginine-related metabolism were common metabolic pathways for both medications. Lysophosphatidylcholine （16∶1/0∶0）［LPC （16∶1/ 0∶0）］， phosphatidylcholine （15∶0/15∶0）［PC （15∶0/15∶0）］ were the key metabolites of glycerophospholipid metabolic pathway； ornithine， spermidine were the key metabolites of arginine-related metabolic pathway. The tricarboxylic acid cycle and glutathione metabolism were the unique metabolic pathways of

Yiqi Liangxue Shengji Formula

. Compared with the sham-surgery group， LPC （16∶1/0∶0）， ornithine， and spermidine levels elevated and PC （15∶0/15∶0） levels decreased in the model group （

＜0.05 or

＜0.01）. Compared with the model group， LPC （16∶1/0∶0）， ornithine， and spermidine levels decreased， and PC （15∶0/15∶0） levels increased in both TCM group and atorvastatin group （

＜0.05 or

＜0.01）. The degree of LPC reduction （16∶1/0∶0） was more significant in atorvastatin group compared with that in the TCM group （

＜0.01）.

Conclusions

Both sham-surgery and atorvastatin could regulate lipid metabolism and arginine-related metabolism， exert the characteristics of lipid-lowering， anti-inflammatory， improve arginine/NO bioavailability， and improve endothelial dysfunction. Atorvastatin showed more advantages in lipid-lowering and anti-inflammatory， whi

Yiqi Liangxue Shengji Formula

has unique characteristics in regulating energy metabolism and improving oxidative stress.

关键词

Keywords

references

LAWTON JS ， TAMIS-HOLLAND JE ， BANGALORE S ， et al . 2021 ACC/AHA/SCAI guideline for coronary artery revascularization： executive summary： a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines ［J］. Circulation ， 2022 ， 145 （ 3 ）： e4 - e7 .

NEUMANN FJ ， SOUSA-UVA M ， AHLSSON A ， et al . 2018 ESC/EACTS Guidelines on myocardial revascularization ［J］. Eur Heart J ， 2019 ， 40 （ 2 ）： 87 - 165 .

NISSEN SE ， TUZCU EM ， SCHOENHAGEN P ， et al . Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis： a randomized controlled trial ［J］. JAMA ， 2004 ， 291 （ 9 ）： 1071 - 1080 .

DAVIGNON J . Beneficial cardiovascular pleiotropic effects of statins ［J］. Circulation ， 2004 ， 109 （ 23 ）： Ⅲ39 -Ⅲ43.

MACIN SM ， PERNA ER ， FARÍAS EF ， et al . Atorvastatin has an important acute anti-inflammatory effect in patients with acute coronary syndrome： results of a randomized， double-blind， placebo-controlled study ［J］. Am Heart J ， 2005 ， 149 （ 3 ）： 451 - 457 .

ZHENG D ， LIANG Q ， ZENG F ， et al . Atorvastatin protects endothelium by decreasing asymmetric dimethylarginine in dyslipidemia rats ［J］. Lipids Health Dis ， 2015 ， 14 ： 41 . doi： 10.1186/s12944-015-0041-2 http://dx.doi.org/10.1186/s12944-015-0041-2 .

MADHAWAN MV ， KIRTANE AJ ， REDFORS B ， et al . Stent-related adverse events ＞1 year after percutaneous coronary intervention ［J］. J Am Coll Cardiol ， 2020 ， 75 （ 6 ）： 590 - 604 .

马征，龙佳，贾文浩，等 . 益气凉血生肌方预防冠心病PCI术后气虚血瘀、痰热互结证患者主要不良心血管事件的随机对照试验［J］. 中医杂志， 2019 ， 60 （ 21 ）： 1837 - 1842 .

贾文浩，万洁，马征，等 . 益气凉血生肌方对PCI术后中医症状及证候要素影响的研究［J］. 世界中西医结合杂志， 2021 ， 16 （ 2 ）： 229 - 232 .

苏菲，万洁，董巧稚，等 . 从10年随访探讨益气凉血生肌方改善PCI术后生存质量的跟踪研究［J］. 世界中医药， 2016 ， 11 （ 3 ）： 395 - 397，401 .

李颖妃，黄雁超，金刚，等 . 益气凉血生肌方基于TLR4/NF-κB通路减轻内皮细胞炎症损伤的研究［J］. 现代中西医结合杂志， 2022 ， 31 （ 7 ）： 882 - 887 .

汪吴娇，刘璐，龙佳，等 . 基于mTOR1信号通路研究益气凉血生肌方对人脐静脉内皮细胞缺氧/复氧损伤的保护作用［J］. 现代中西医结合杂志， 2023 ， 32 （ 1 ）： 10 - 14，37 .

MULLER DW ， ELLIS SG ， TOPOL EJ . Experimental models of coronary artery restenosis ［J］. J Am Coll Cardiol ， 1992 ， 19 （ 2 ）： 418 - 432 .

NAIR A ， MORSY MA ， JACOB S . Dose translation between laboratory animals and human in preclinical and clinical phases of drug development ［J］. Drug Dev Res ， 2018 ， 79 （ 8 ）： 373 - 382 .

郝伟，赵晨，胡思宁，等 . 冠状动脉药物洗脱支架内再狭窄的最新研究进展［J］. 中国介入心脏病学杂志， 2023 ， 31 （ 1 ）： 63 - 68 .

李建军 . 血脂异常与动脉粥样硬化关系的现代观念［J］. 中国循环杂志， 2022 ， 37 （ 3 ）： 212 - 214 .

NISSEN SE . Effect of intensive lipid lowering on progression of coronary atherosclerosis： evidence for an early benefit from the Reversal of Atherosclerosis with Aggressive Lipid Lowering（REVERSAL） trial ［J］. Am J Cardiol ， 2005 ， 96 （ 5A ）： 61 F-68F.

KAMISHIRADO H ， INOUE T ， SAKUMA M ， et al . Effects of statins on restenosis after coronary stent implantation ［J］. Angiology ， 2007 ， 58 （ 1 ）： 55 - 60 .

LU J ， CHEN B ， CHEN T ， et al . Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases ［J］. Redox Biol ， 2017 ， 12 ： 899 - 907 . doi： 10.1016/j.redox.2017.04.032 http://dx.doi.org/10.1016/j.redox.2017.04.032 .

SCHMITZ G ， RUEBSAAMEN K . Metabolism and atherogenic disease association of lysophosphatidylcholine ［J］. Atherosclerosis ， 2010 ， 208 （ 1 ）： 10 - 18 .

ZHOU X ， WANG R ， ZHANG T ， et al . Identification of lysophosphatidylcholines and sphingolipids as potential biomarkers for acute aortic dissection via serum metabolomics ［J］. Eur J Vasc Endovasc Surg ， 2019 ， 57 （ 3 ）： 434 - 441 .

LIU P ， ZHU W ， CHEN C ， et al . The mechanisms of lysophosphatidylcholine in the development of diseases ［J］. Life Sci ， 2020 ， 247 ： 117443 . doi： 10.1016/j.lfs. 2020.117443 http://dx.doi.org/10.1016/j.lfs.2020.117443 .

PALMER RM ， ASHTON DS ， MONCADA S . Vascular endothelial cells synthesize nitric oxide from L-arginine ［J］. Nature ， 1988 ， 333 （ 6174 ）： 664 - 666 .

KHADDAJ MR ， MATHEW JC ， KENDRICK DJ ， et al . The vascular endothelium： a regulator of arterial tone and interface for the immune system ［J］. Crit Rev Clin Lab Sci ， 2017 ， 54 （ 7-8 ）： 458 - 470 .

FORTE A ， HELLSTRAND P ， NILSSON BO ， et al . The polyamine pathway as a potential target for vascular diseases： focus on restenosis ［J］. Curr Vasc Pharmacol ， 2011 ， 9 （ 6 ）： 706 - 714 .

TANG WHW ， WANG Z ， CHO L ， et al . Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk ［J］. J Am Coll Cardiol ， 2009 ， 53 （ 22 ）： 2061 - 2067 .

NISHIDA K ， ABIKO T ， ISHIHARA M ， et al . Arterial injury-induced smooth muscle cell proliferation in rats is accompanied by increase in polyamine synthesis and level ［J］. Atherosclerosis ， 1990 ， 83 （ 2-3 ）： 119 - 125 .

SHIMIZU H ， KIYOHARA Y ， KATO I ， et al . Relationship between plasma glutathione levels and cardiovascular disease in a defined population： the Hisayama study ［J］. Stroke ， 2004 ， 35 （ 9 ）： 2072 - 2077 .

MURAKI A ， MIYASHITA K ， MITSUISHI M ， et al . Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endu-rance ［J］. J Appl Physiol （1985）， 2012 ， 113 （ 3 ）： 479 - 486 .

林谦，霍艳明，郭维琴，等 . 心气虚证中医辨证规律的临床研究［J］. 中西医结合杂志， 1990 ， 10 （ 2 ）： 78 - 81，68 .

韩晶岩 . 心气虚血瘀的科学内涵和芪参益气滴丸补气活血的作用机理［J］. 世界科学技术-中医药现代化， 2019 ， 21 （ 2 ）： 139 - 147 .

查看原文

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Analysis of Clinical and Phenomics Characteristics of Patients with Phlegm-Stasis Binding Syndrome and Its Accompanied Patterns in Stable Angina Pectoris of Coronary Heart Disease

Construction and Validation of a Clinical Prediction Model for Inflammatory Remission Outcome of Bushen Zhiwang Decoction（补肾治尪汤）in the Treatment of Rheumatoid Arthritis with Liver and Kidney Deficiency Syndrome

Prevention and Treatment of Post-Percutaneous Coronary Intervention Coronary Microvascular Dysfunction from the Perspective of "Deficiency Qi Retention and Stagnation"

Effects of Spleen Deficiency on Lipid Metabolism in Hyperlipidemia Model Rats Based on Gut Microbiota Sequencing and Fecal Metabolomics

A Multi-Omics Study on the Differences in Blood Biological Characteristics between Acute Gout Patients with Damp-Heat Toxin Accumulation Syndrome and Damp-Heat Accumulation Syndrome

Related Author

LI Chongchai

LI Han

LI Zheng

LI Zeng

ZHOU Yushi

AO Yuhan

XU Shuang

WANG Xue

Related Institution

Dongfang Hospital，Beijing University of Chinese Medicine

Clinical Evaluation Center，China Academy of Chinese Medical Sciences

Affiliated Hospital of Liaoning University of Traditional Chinese Medicine

Shenyang Health Service Center

Liaoning University of Traditional Chinese Medicine

Address：No.16, Nanxiao street, Dongzhimen, Dongcheng District, Beijing Postal code：100700
Tel：010-64035632 Email：jtcmcn@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19 京公网安备11010102007558号
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

Comparative Study on Effect of Yiqi Liangxue Shengji Formula （益气凉血生肌方） and Atorvastatin Tablets on Vascular Injury and Differences in Serum Metabolites in Abdominal Aortic Balloon Injury Model Rats

DOI：10.13288/j.11-2166/r.2024.11.016

摘要

Abstract

关键词

Keywords

references