Protective Effect of Jianpi Huogu Prescription on Functional Injury of Vascular Endothelial Cells Caused by Alcohol Based on Akt/JNK/p38 MAPK Signaling Pathway

WANG Xiaoxiao; HE Lianhua; FANG-LUO Changting; LI Qun; YANG Chao; HU Zhixing; CHEN Weiheng; LIU Chunfang; HAN Lan; LIN Na

doi:10.13422/j.cnki.syfjx.20230442

您当前的位置：

首页 >

文章列表页 >

Protective Effect of Jianpi Huogu Prescription on Functional Injury of Vascular Endothelial Cells Caused by Alcohol Based on Akt/JNK/p38 MAPK Signaling Pathway

更新时间：2023-04-28

- Protective Effect of Jianpi Huogu Prescription on Functional Injury of Vascular Endothelial Cells Caused by Alcohol Based on Akt/JNK/p38 MAPK Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 11, Pages: 64-71(2023)
- 作者机构：
  
  1.安徽中医药大学药学院，合肥 230012
  2.中国中医科学院中药研究所，北京 100700
  3.北京中医药大学第三附属医院，北京 100029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230442
  CLC： R2-0;R33;R289;R742
- Published：05 June 2023，
  
  Published Online：22 March 2023，
  
  Received：17 February 2023，
- 稿件说明：
扫描看全文
王潇潇,何莲花,方罗昌婷等.基于Akt/JNK/p38 MAPK信号通路探讨健脾活骨方对酒精致血管内皮细胞功能损伤的保护作用[J].中国实验方剂学杂志,2023,29(11):64-71.

WANG Xiaoxiao,HE Lianhua,FANG-LUO Changting,et al.Protective Effect of Jianpi Huogu Prescription on Functional Injury of Vascular Endothelial Cells Caused by Alcohol Based on Akt/JNK/p38 MAPK Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(11):64-71.
王潇潇,何莲花,方罗昌婷等.基于Akt/JNK/p38 MAPK信号通路探讨健脾活骨方对酒精致血管内皮细胞功能损伤的保护作用[J].中国实验方剂学杂志,2023,29(11):64-71. DOI： 10.13422/j.cnki.syfjx.20230442.

WANG Xiaoxiao,HE Lianhua,FANG-LUO Changting,et al.Protective Effect of Jianpi Huogu Prescription on Functional Injury of Vascular Endothelial Cells Caused by Alcohol Based on Akt/JNK/p38 MAPK Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(11):64-71. DOI： 10.13422/j.cnki.syfjx.20230442.

摘要

目的

观察健脾活骨方（JPHGP）对酒精致血管内皮细胞功能损伤的保护作用，并基于蛋白激酶B/c-Jun氨基末端激酶/p38 MAPK（Akt/JNK/p38 MAPK）信号通路探索相关作用机制。

方法

通过鸡胚尿囊膜实验、胸主动脉环实验和人脐静脉内皮细胞（HUVEC）的迁移、侵袭、黏附和管腔形成实验，在有或无酒精诱导条件下，观察JPHGP不同质量浓度8、16、32 μg·L

-1

对血管新生的影响；采用蛋白免疫印迹法（Western blot）检测HUVEC中Akt、JNK、p38 MAPK等磷酸化表达水平。

结果

与正常组比较，模型组动脉环周围微血管数目及长度均减少，HUVEC的迁移、侵袭、和管腔形成能力降低（

0.05，

0.01）；JPHGP 16、32 μg·L

-1

组作用后能明显升高鸡胚尿囊膜新生血管长度（

0.05，

0.01），与模型组比较，JPHGP 8、16、32 μg·L

-1

组能浓度依赖地增加胸主动脉环周围微血管数量（

0.05，

0.01），JPHGP 32 μg·L

-1

组能升高胸主动脉环周围微血管长度（

0.05）；JPHGP 16、32 μg·L

-1

组均能增强HUVEC的迁移、侵袭、和管腔形成能力。Western blot检测结果表明，与正常组比较，模型组中的p-JNK/JNK、p-p38 MAPK/p38 MAPK、p-Akt/Akt蛋白表达水平均显著降低（

0.01）；与模型组比较，JPHGP 8、16、32 μg·L

-1

组的p-p38 MAPK/p38 MAPK、p-Akt/Akt蛋白表达水平均显著升高（

0.01），JPHGP 16、32 μg·L

-1

组的p-JNK/JNK的蛋白表达水平显著升高（

0.01）。

结论

JPHGP对酒精致血管内皮细胞功能损伤具有保护作用，其机制可能与激活Akt/JNK/p38 MAPK信号通路有关，相关研究结果将为JPHGP“健脾活血”功效阐明提供一定的科学依据。

Abstract

Objective

To investigate the protective effect of Jianpi Huogu prescription （JPHGP） on the functional injury of vascular endothelial cells caused by alcohol and explore its mechanism based on protein kinase B/c-Jun amino-terminal kinase/p38 MAPK （Akt/JNK/p38 MAPK） signaling pathway.

Method

Through chick embryo allantoic membrane， thoracic aortic ring， and migration， invasion， adhesion， and lumen formation of human umbilical vein endothelial cells （HUVEC）， the effect of JPHGP with different concentrations （8， 16 and 32 μg·L

-1

） on angiogenesis was observed in the presence or absence of alcohol. The expression levels of phosphorylation of Akt， JNK， and p38 MAPK were determined by Western blot.

Result

As compared with the normal group， the number and length of capillaries around the arterial ring in the model group were decreased， and the migration， invasion， and lumen formation capacity of HUVEC were decreased （

0.05，

0.01）. After treatment with 16 and 32 μg·L

-1

JPHGP， the length of neovascularization in chick embryo allantoic membrane was significantly increased （

0.05，

0.01）. Compared with the model group， the 8， 16， and 32 μg·L

-1

JPHGP groups increased the number of capillaries around the thoracic aortic ring in a concentration-dependent manner （

0.05，

0.01）， and the 32 μg·L

-1

JPHGP group increased the length of capillaries around the thoracic aortic ring （

0.05）. The 16 and 32 μg·L

-1

JPHGP groups enhanced the migration， invasion， and lumen formation capacity of HUVEC. The results of Western blot showed that， as compared with the normal group， the protein expression levels of p-JNK/JNK， p-p38 MAPK/p38 MAPK， and p-Akt/Akt were significantly decreased in the model group （

0.01）， and as compared with the model group， the protein expression levels of p-p38 MAPK/p38 MAPK and p-Akt/Akt were significantly increased in the 8， 16， and 32 μg·L

-1

JPHGP groups （

0.01） and the protein expression level of p-JNK/JNK was increased significantly in the 16 and 32 μg·L

-1

JPHGP groups （

0.01）.

Conclusion

JPHGP has a protective effect on the functional injury of vascular endothelial cells caused by alcohol， and its mechanism may be related to the activation of Akt/JNK/p38 MAPK signaling pathway. Relevant research results will provide certain scientific basis for clarifying the effect of JPHGP on 'invigorating spleen and promoting blood circulation'.

关键词

健脾活骨方人脐静脉内皮细胞蛋白激酶B/c-Jun氨基末端激酶/p38 MAPK（Akt/JNK/p38 MAPK）信号通路血管生成

Keywords

Jianpi Huogu prescriptionhuman umbilical vein endothelial cellsprotein kinase B/c-Jun amino-terminal kinase/p38 MAPK （Akt/JNK/p38 MAPK） signaling pathwaysangiogenesis

references

周占国，郭浩山，关涛，等.股骨头坏死病因的相关因素分析［J］.中医正骨，2020，32（1）：7-10.

ZHAO D，ZHANG F，WANG B，et al.Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults （2019 version）［J］.J Orthop Translat，2020，21：100-110.

CHEN X， LI M， YAN J K， et al. Alcohol induces cellular senescence and impairs osteogenic potential in bone Marrow-derived mesenchymal stem cells［J］. Alcohol Alcohol，2017，52（3）： 289-297．

刘铁钢，陈卫衡.非创伤性股骨头坏死的流行病学研究进展［J］.医学综述，2009，15（17）：2637-2639.

KONG X，LI X，ZHANG C，et al.Ethyl acetate fraction of Huogu formula inhibits adipogenic differentiation of bone marrow stromal cells via the BMP and Wnt signaling pathways［J］.Int J Biol Sci，2017，13（4）：480-491.

KONG X，LI X，ZHANG C，et al.Aqueous fraction of Huogu formula promotes osteogenic differentiation of bone marrow stromal cells through the BMP and Wnt signaling pathways［J］.Rejuvenation Res，2016，19（6）：509-520.

JIANG Y，LIU D，KONG X，et al.Huogu Ⅰ formula prevents steroid-induced osteonecrosis in rats by down-regulating PPARgamma expression and activating Wnt/LRP5/beta-catenin signaling［J］.J Tradit Chin Med，2014，34（3）：342-350.

CHEN W H，KONG X Y，WAN R，et al.Effects of huogu Ⅰ formula （Ⅰ） on correlated factors of bone regeneration in chickens with steroid-induced necrosis of femoral head［J］.Chin J Integr Med，2012，18（5）：378-384.

徐腾腾，王金霞，明瑞蕊，等.健脾活骨方对糖皮质激素致血管内皮细胞功能损伤的干预作用［J］.中国中药杂志，2022，47（6）：1625-1631.

惠银银，刘又斌，王晶，等.非创伤性股骨头坏死病因的研究进展［J］.中医正骨，2018，30（2）：33-36，40.

方罗昌婷，汪倩倩，孙丛丛，等.基于VEGF/VEGFR2/PI3K/Akt信号通路研究健脾活骨方对AONFH血管损伤的修复作用机制［J］.中国实验方剂学杂志，2023，29（8）：186-194.

LI Q，WANG Z.Influence of mesenchymal stem cells with endothelial progenitor cells in co-culture on osteogenesis and angiogenesis：An in vitro study［J］.Arch Med Res，2013，44（7）：504-513.

PEACH CJ， MIGNONE VW， ARRUDA MA， et al.Molecular pharma-cology of VEGF-A isoforms： Binding and signalling at VEGFR2［J］.Int J Mol Sci， 2018，19：1264.

MELINCOVICI C S，BOŞCA A B，ŞUŞMAN S，et al.Vascular endothelial growth factor （VEGF）-key factor in normal and pathological angiogenesis［J］.Rom J Morphol Embryol，2018，59（2）：455-467.

谭婕，李芃，王洪星，等.加味阳和汤对阳虚寒凝型酒精性股骨头坏死大鼠PI3K、Akt基因及蛋白表达水平的影响［J］.临床合理用药杂志，2022，15（36）：118-121.

马文元，吴智恒，吴洁，等.股骨头坏死信号通路研究概述［J］.中国医药科学，2022，12（18）：26-29，90.

SONG F，HU B，CHENG J W，et al.Anlotinib suppresses tumor progression via blocking the VEGFR2/PI3K/Akt cascade in intrahepatic cholangiocarcinoma［J］.Cell Death Dis，2020，11（7）：573.

史桂荣，任博文，张仲博，等.红茴香提取物干预骨质疏松性大鼠骨折后的血管生成［J］.中国组织工程研究，2023，27（31）：5028-5034.

AGAS D，HANNA R，BENEDICENTI S，et al.Photobiomodulation by near-infrared 980-nm wavelengths regulates pre-osteoblast proliferation and viability through the PI3K/Akt/Bcl-2 pathway［J］.Int J Mol Sci，2021，22（14）：7586.

耿军辉，张丽军，王亚丽，等.PI3K/Akt信号通路与肿瘤血管新生的研究进展［J］.现代肿瘤医学，2018，26（9）：1462-1466.

周毅，杨世鹏，赵智慧，等.川骨片对家兔激素性股骨头缺血性坏死ERK1/2、JNK、p38磷酸化蛋白的影响［J］.广州中医药大学学报，2019，36（11）：1808-1813.

SUZUKI A，GUICHEUX J，PALMER G，et al.Evidence for a role of p38 MAP kinase in expression of alkaline phosphatase during osteoblastic cell differentiation［J］.Bone，2002，30（1）：91-98.

李登举，张瑶珍.JNK和p38通路与正常及异常造血［J］.国外医学：生理、病理科学与临床分册，2001，21（4）：264-265.

田能，孔祥英，万蓉，等.健脾活血方对激素性股骨头坏死血管内皮生长因子表达的影响［J］.中国实验方剂学杂志，2010，16（2）：48-51.

李泰贤，张彦琼，黄泽青，等.从分子网络解析非创伤性股骨头坏死不同中医证候的生物学基础及其对证方药的作用机制［J］.中国实验方剂学杂志，2020，26（16）：192-204.

沈莹姗，乌日莎娜，庄至坤，等.基于病理表型辨析激素性与酒精性股骨头坏死的血瘀证特点［J］.中华中医药杂志，2021，36（8）：4868-4872.

魏秋实，杨帆，陈哓俊，等.激素性与酒精性股骨头坏死患者骨标本坏死区域病理与显微结构特点分析［J］.中国修复重建外科杂志，2018，32（7）：866-872.

王金霞，贾可欣，明瑞蕊，等.通络生骨胶囊对糖皮质激素致血管内皮细胞功能损伤的保护作用［J］.中国实验方剂学杂志，2021，27（9）：48-55.

徐传毅.袁浩教授从血瘀证论治激素性股骨头坏死经验［J］.中医药学刊，2003，21（2）：194-195.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect and Mechanism of Curcumin on Melanoma Growth and Angiogenesis

Effect of Gualou Xiebai Banxiatang on Myocardial Microangiogenesis and HIF-1α/VEGF-related Pathways in Myocardial Ischemia Model Rats

Role of MAPK Signaling Pathway in Prevention and Treatment of Rheumatoid Arthritis and Chinese Medicine Intervention： A Review

In Vitro and in Vivo Evaluation of Scutellarin-phospholipid Complex Nanoemulsion and Analysis of Its Activity in Ameliorating LPS-induced Vascular Endothelial Injury

Related Author

QIN Jian-wei

CHEN Lin

CHEN Wenhao

MENG Weishan

LI Hong

TIAN Weiwei

ZHANG Qi

TAN Yingying

Related Institution

The Second Affiliated Hospital of Henan University of Science and Technology

Basic Medical College，Shaanxi University of Chinese Medicine

Gansu University of Chinese Medicine

Gansu Provincial Hospital of Traditional Chinese Medicine

Guizhou Provincial Food and Drug Inspection Institute

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