Effect of Astragaloside Ⅳ Combined with Notoginseng Total Saponins on Angiogenesis After Transplantation of BMSCs in Rats with Cerebral Ischemia

Yan-ling LI; Huang DING; Fu-rong YANG; Zhan-hui LU; Yu-wen LI; Xiao-dan LIU; Chang-qing DENG

doi:10.13422/j.cnki.syfjx.20212138

您当前的位置：

首页 >

文章列表页 >

Effect of Astragaloside Ⅳ Combined with Notoginseng Total Saponins on Angiogenesis After Transplantation of BMSCs in Rats with Cerebral Ischemia

更新时间：2021-10-14

- Effect of Astragaloside Ⅳ Combined with Notoginseng Total Saponins on Angiogenesis After Transplantation of BMSCs in Rats with Cerebral Ischemia
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 21, Pages: 73-79(2021)
- 作者机构：
  
  湖南中医药大学中西医结合心脑疾病防治湖南省重点实验室，细胞生物学与分子技术湖南省高校重点实验室，长沙 410208
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20212138
  CLC： R2-0;R289;R33;R743.31
- Received：24 July 2021，
  
  Published Online：24 September 2021，
  
  Published：05 November 2021
- 稿件说明：
移动端阅览
李艳玲,丁煌,杨芙蓉等.黄芪甲苷配伍三七总皂苷对脑缺血大鼠BMSCs移植后血管新生的影响[J].中国实验方剂学杂志,2021,27(21):73-79.

LI Yan-ling,DING Huang,YANG Fu-rong,et al.Effect of Astragaloside Ⅳ Combined with Notoginseng Total Saponins on Angiogenesis After Transplantation of BMSCs in Rats with Cerebral Ischemia[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(21):73-79.
李艳玲,丁煌,杨芙蓉等.黄芪甲苷配伍三七总皂苷对脑缺血大鼠BMSCs移植后血管新生的影响[J].中国实验方剂学杂志,2021,27(21):73-79. DOI： 10.13422/j.cnki.syfjx.20212138.

LI Yan-ling,DING Huang,YANG Fu-rong,et al.Effect of Astragaloside Ⅳ Combined with Notoginseng Total Saponins on Angiogenesis After Transplantation of BMSCs in Rats with Cerebral Ischemia[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(21):73-79. DOI： 10.13422/j.cnki.syfjx.20212138.

摘要

目的

探讨黄芪甲苷（AST Ⅳ）与三七总皂苷（NTS）配伍联合骨髓间充质干细胞移植对脑缺血大鼠神经修复和血管新生的影响。

方法

大鼠随机分为假手术组，模型组，AST Ⅳ配伍NTS低、高剂量组，骨髓间充质干细胞（BMSCs）输注组，BMSCs输注联合黄芪甲苷和三七总皂苷低（10，25 mg·kg

-1

），高（20，50 mg·kg

-1

）剂量组。全骨髓贴壁法分离、纯化BMSCs，流式细胞术检测BMSCs表面标志物CD29，CD90，CD34，CD45阳性表达率。采用大脑中动脉阻塞建立局灶性脑缺血模型。BMSCs输注组尾静脉注射PKH26标记的BMSCs（1次/d）；联用组尾静脉注射BMSCs（1次/d）并灌胃给药（2次/d）；其他组灌胃给药，2次/d；假手术组、模型组灌胃等体积生理盐水。Longa法测定神经功能缺损症状，红四氮唑（TTC）染色测定脑梗死率、免疫荧光法观察BMSCs移植后的存活及向血管的分化［PKH26/血管内皮生长因子（VEGF）的双阳性表达］，蛋白免疫印迹法（Western blot）检测血管生成素1（Ang1）和转化生长因子-

（TGF-

）蛋白的表达。

结果

成功分离培养BMSCs，表面标志物CD29，CD90，CD34，CD45鉴定符合BMSCs特征。脑缺血后出现神经功能缺损症状，模型组神经功能缺损评分显著升高（

0.01），脑梗死率显著增高（

0.01），各药物及细胞移植均能不同程度减轻上述病理改变，其中效应最强为BMSCs输注联合高剂量AST Ⅳ+NTS组（

0.01），优于单用药物和单用BMSCs输注。脑缺血后脑血管损伤，输注BMSCs后，细胞可在缺血侧脑组织存活并促进血管新生，药物联合可增强其效应。脑缺血后，Ang1和TGF-

的表达增加，效应最强为BMSCs输注联合AST Ⅳ+NTS组（

0.01），优于单用药物和单用BMSCs输注。

结论

AST Ⅳ配伍NTS能促进骨髓间充质干细胞移植的存活，靶向修复脑缺血后受损血管促进血管新生，机制可能与改善脑缺血后脑内局部微环境，促进移植干细胞的存活和分化有关。

Abstract

Objective

To investigate the effect of astragaloside Ⅳ（AST Ⅳ）and Notoginseng total saponins （NTS） combined with bone marrow mesenchymal stem cell （BMSC） transplantation on neural repair and angiogenesis in rats with cerebral ischemia.

Method

The rats were randomly divided into a sham operation group， a model group， low- and high-dose AST Ⅳ + NTS groups， a BMSC infusion group， and low- and high-dose BMSC infusion+AST Ⅳ （10 and 20 mg·kg

-1

） + NTS group （25， 50 mg·kg

-1

）. BMSCs were isolated and purified by whole bone marrow adherent culture. The positive expression of surface markers of BMSCs （CD29， CD90， CD34， and CD45） was detected by flow cytometry. The focal cerebral ischemia model was established by middle cerebral artery occlusion （MCAO）. The PKH26-labeled BMSCs were injected into the tail vein of rats in the BMSC infusion group， once a day. The rats in the combination groups received BMSC injection once a day and intragastric administration of drugs twice a day. Other groups were administered twice a day by gavage. The sham operation group and the model group received the same amount of normal saline. Symptoms and signs of neurological deficits were assessed by the Longa method and the cerebral infarction rate was determined by TTC staining. The survival and vascularization ［double positive expression of PKH26/vascular endothelial growth factor （VEGF）］ after transplantation of BMSCs were observed by the immunofluorescence method. The protein expression of Ang1 and TGF-

was measured by Western blot.

Result

BMSCs were properly isolated and cultured. The identification of surface markers CD29， CD90， CD34， and CD45 was consistent with the characteristics of BMSCs. The neurological deficit score and cerebral infarction rate of the model group were significantly increased （

0.01）. All drugs and cell transplantation could alleviate the above pathological changes in varying degrees. The strongest effect was observed in high-dose BMSC infusion+AST Ⅳ+NTS group （

0.01）， which was superior to those in the AST Ⅳ+NTS groups or the BMSC infusion group. BMSC injection helped cells survive in the ischemic brain tissues and promoted angiogenesis， and this effect could be enhanced by the combination with drugs. After cerebral ischemia， the expression of Ang1 and TGF-

was increased， and the effect in the BMSC infusion+AST Ⅳ+NTS groups was the strongest （

0.01）.

Conclusion

AST Ⅳ combined with NTS can promote the survival of transplanted BMSCs and facilitate angiogenesis after target repair of damaged blood vessels after cerebral ischemia. The mechanism may be related to the improvement of the local microenvironment in the brain after cerebral ischemia and the promotion of the survival and differentiation of transplanted stem cells.

关键词

Keywords

references

IRVINE H J ， OSTWALDT A C ， BEVERS M B ， et al . Reperfusion after ischemic stroke is associated with reduced brain edema ［J］. Cereb Blood Flow Metab ， 2018 ， 38 （ 10 ）： 1807 - 1817 .

CHUNG J W ， CHANG W H ， BANG O Y ， et al . Efficacy and safety of intravenous mesenchymal stem cells for ischemic stroke ［J］. Neurology ， 2021 ， 96 （ 7 ）： e1012 - e1023 .

BHATIA V ， GUPTA V ， KHURANA D ， et al . Randomized assessment of the safety and efficacy of intra-arterial infusion of autologous stem cells in subacute ischemic stroke ［J］. AJNR Am J Neuroradiol ， 2018 ， 39 （ 5 ）： 899 - 904 .

DENG L ， PENG Q ， WANG H ， et al . Intrathecal injection of allogenic bone marrow-derived mesenchymal stromal cells in treatment of patients with severe ischemic stroke：study protocol for a randomized controlled observer-blinded trial ［J］. Transl Stroke Res ， 2019 ， 10 （ 2 ）： 170 - 177 .

江羽，王叶叶，梁晨，等 . 经木香烃内酯诱导的骨髓间充质干细胞用于治疗脑缺血再灌注损伤的研究［J］. 世界科学技术—中医药现代化， 2019 ， 21 （ 4 ）： 573 - 579 .

刘晓丹，黄小平，邓常清，等 . 冰片对黄芪甲苷和三七总皂苷配伍有效成分在脑缺血/再灌注模型大鼠脑组织分布的影响［J］. 中草药， 2019 ， 50 （ 7 ）： 1649 - 1656 .

黄小平，谭华，邓常清，等 . 黄芪总苷和三七总皂苷配伍对脑缺血再灌注后MMP-9和TIMP-1表达的影响［J］. 中国中药杂志， 2010 ， 35 （ 16 ）： 2187 - 2191 .

丁煌，黄小平，邓常清，等 . 冰片配伍黄芪甲苷与三七总皂苷对脑缺血/再灌注后血脑屏障通透性的影响［J］. 中国药理学通报， 2019 ， 35 （ 11 ）： 1516 - 1523 .

LONGA E Z ， WEINSTEIN P R ， CARLSON S ， et al . Reversible middle cerebral artery occlusion without craniectomy in rats ［J］. Stroke ， 1989 ， 20 （ 1 ）： 84 - 91 .

欧阳波，黄小平，邓常清，等 . 冰片配伍黄芪甲苷和三七总皂苷通过Notch信号通路对大鼠脑缺血再灌注损伤模型的神经保护作用［J］. 中草药， 2020 ， 51 （ 23 ）： 5990 - 5997 .

BRICK R M ， SUN A X ， TUAN R S . Neurotrophically induced mesenchymal progenitor cells derived from induced pluripotent stem cells enhance neuritogenesis via neurotrophin and cytokine production ［J］. Stem Cells Transl Med， 2018 ， 7 （ 1 ）： 45 - 58 .

DELCROIX G J ， GARBAYO E ， SINDJI L ， et al . The therapeutic potential of human multipotent mesenchymal stromal cells combined with pharmacologically active microcarriers transplanted in hemi-parkinsonian rats ［J］. Biomaterials ， 2011 ， 32 （ 6 ）： 1560 - 1573 .

孔令提，宋春丽，石庆平 . 人参皂苷对脑缺血再灌注损伤的保护机制研究现状［J］. 中国药房， 2019 ， 30 （ 17 ）： 2445 - 2448 .

唐敏英，雷艳，吴仲秋，等 . 三维培养的间充质干细胞球体的生物学特性及应用的研究进展［J］. 中华细胞与干细胞杂志， 2020 ， 10 （ 5 ）： 314 - 318 .

ROMPOLAS P ， MESA K R ， GRECO V . Spatial organization within a niche as a determinant of stem-cell fate ［J］. Nature ， 2013 ， 502 （ 7472 ）： 513 - 518 .

HUANG X P ， DING H ， DENG C Q ， et al . Effects of the combination of the main active components of astragalus and panax notoginseng on inflammation and apoptosis of nerve cell after cerebral ischemia-reperfusion ［J］. Am J Chin Med ， 2015 ， 43 （ 7 ）： 1419 .

黄小平，刘晓丹，邓常清 . 黄芪和三七主要有效成分配伍对氧化损伤所致的PC12细胞凋亡及其活性氧、线粒体膜电位的影响［J］. 中西医结合学报， 2012 ， 10 （ 10 ）： 1127 - 1134 .

HUANG X P ， DING H ， YANG X Q ， et al . Synergism and mechanism of astragaloside Ⅳ combined with ginsenoside Rg 1 against autophagic injury of PC12 cells induced by oxygen glucose deprivation/reoxygenation ［J］. Biomed Pharmacother ， 2017 ， 89 ： 124 - 134 .

DAVIS S ， ALDRICH T H ， JONES P F ， et al . Isolation of angiopoietin-1，a lligand for the TIE2 receptor，by secretion-trap expression cloning ［J］. Cell ， 1996 ， 87 （ 7 ）： 1161 - 1169 .

YU Y ， LI J ， ZHOU H ， et al . Functional importance of the TGF- β 1 /Smad3 signaling pathway in oxygen-glucose-deprived（OGD）microglia and rats with cerebral ischemia ［J］. Int J Biol Macromol ， 2018 ， 116 ： 537 - 544 .

LEE Y C ， KAO S T ， CHENG C Y . Acorus tatarinowii schott extract reduces cerebral edema caused by ischemia-reperfusion injury in rats：involvement in regulation of astrocytic NKCC1/AQP4 and JNK/iNOS-mediated signaling ［J］. BMC Complement Med Ther ， 2020 ， 20 （ 1 ）： 374 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Analysis of Mechanism of Astragaloside Ⅳ in Regulating Ferroptosis Through SLC7A11/GPX4 Pathway Against Vascular Smooth Muscle Cell Proliferation

Multidimensional Analysis of Mechanisms of Nuciferine Against Cerebral Ischemia Based on Transcriptomic Data

Mechanism of Astragaloside Ⅳ in Regulating PI3K/Akt Molecular Pathway in Prevention and Treatment of Diabetes Complications： A Review

Effect of Compatibility of Effective Monomer Components of Fujin Shengjisan on Angiogenesis of HUVEC Based on Uniform Design

Mechanism of Chinese Medicine in Promoting Angiogenesis After Ischemic Stroke Based on PI3K/Akt Signaling Pathway： A Review

Related Author

LI Guoting

YANG Changchao

LIU Lin

LI Weikang

ZHAO Zixian

SHEN Quan

ZHAO Jingshan

QIN Yingying

Related Institution

Hebei Key Laboratory of Traditional Chinese Medicine（TCM） Research on Cardiocerebrovascular Disease，TCM Processing Technology Innovation Center of Hebei Province，College of Pharmacy， Hebei University of Chinese Medicine

Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences

School of Basic Science，Shanxi Key Laboratory for Modernization of Traditional Chinese Veterinary Medicine，Shanxi Agricultural University

School of Chinese Materia Medica，Chongqing University of Chinese Medicine

Anhui University of Chinese Medicine

AI问答

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
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