Anti⁃fibrosis mechanism of Bushen Rougan Formula inhibiting angiogenesis in mice

Xin WANG; Ziming AN; Huilin DONG; Hongming NIE

doi:10.16306/j.1008-861x.2022.S1.038

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Anti⁃fibrosis mechanism of Bushen Rougan Formula inhibiting angiogenesis in mice

Experiment Research | 更新时间：2022-08-29

- Anti⁃fibrosis mechanism of Bushen Rougan Formula inhibiting angiogenesis in mice
- Academic Journal of Shanghai University of Traditional Chinese Medicine Vol. 36, Issue S1, Pages: 167-173(2022)
- 作者机构：
  
  1.上海中医药大学附属曙光医院肝病研究所（上海　201203）
  2.上海中医药大学附属曙光医院肝病科（上海　201203）
- 作者简介：
- 基金信息：
- DOI：10.16306/j.1008-861x.2022.S1.038
  CLC：
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王欣,安梓铭,董慧琳等.补肾柔肝方抑制血管新生的抗小鼠肝纤维化作用机制[J].上海中医药大学学报,2022,36(S1):167-173.

WANG Xin,AN Ziming,DONG Huilin,et al.Anti⁃fibrosis mechanism of Bushen Rougan Formula inhibiting angiogenesis in mice[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(S1):167-173.
王欣,安梓铭,董慧琳等.补肾柔肝方抑制血管新生的抗小鼠肝纤维化作用机制[J].上海中医药大学学报,2022,36(S1):167-173. DOI： 10.16306/j.1008-861x.2022.S1.038.

WANG Xin,AN Ziming,DONG Huilin,et al.Anti⁃fibrosis mechanism of Bushen Rougan Formula inhibiting angiogenesis in mice[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(S1):167-173. DOI： 10.16306/j.1008-861x.2022.S1.038.

摘要

目的,2,从血管新生角度探讨补肾柔肝方抗小鼠肝纤维化作用机制。,方法,2,雄性C57小鼠按体质量分层随机分为正常组、模型组、补肾柔肝方组、索拉非尼（Sorafenib）组。模型组、补肾柔肝方组、索拉非尼组以0.4%二甲基亚硝胺（DMN）腹腔注射，1次/d，每周3次，共8周，诱导肝纤维化模型。造模第5周开始给药，8周后处死留取血清、肝组织样本。记录小鼠体质量变化及死亡情况；取材后检测血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）及白蛋白（ALB）含量。以天狼猩红胶原染色和肝组织羟脯氨酸（Hyp）含量评估肝纤维化程度；以肝组织血小板内皮细胞粘附分子-1（CD31）和血管内皮生长因子受体2（VEGFR2）蛋白表达情况评价肝脏血管新生情况。,结果,2,模型组小鼠死亡率为15.4%（2/13），补肾柔肝方组无小鼠死亡，索拉非尼组小鼠死亡率7.7%（1/13）。补肾柔肝方组及索拉非尼组小鼠血清ALT、AST含量较模型组降低（,P,<,0.05），血清ALB含量升高（,P,<,0.05）；补肾柔肝方组和索拉非尼组小鼠肝组织Hyp含量较模型组显著降低（,P,<,0.05）。天狼星红染色显示，补肾柔肝方组和索拉非尼组纤维化程度较模型组明显减轻；Western blot及肝组织免疫组化实验显示，补肾柔肝方组和索拉菲尼组小鼠肝组织CD31和VEGFR2蛋白表达较模型组均显著下调（,P,<,0.05）。,结论,2,补肾柔肝方可有效改善DMN诱导小鼠模型肝纤维化，其作用机制可能与抑制血管新生有关。

Abstract

Objective： To investigate the mechanism of Bushen Rougan Formula against hepatic fibrosis from the perspective of angiogenesis.,Methods,2,Male C57 mice were stratified randomly divided into normal group， model group， Bushen Rougan Formula group， Sorafenib group according to body weight. In order to induce liver fibrosis model， the model group， Bushen Rougan Formula group and Sorafenib group were intraperitoneally injected with 0.4% dimethylnitrosamine （DMN） once a day， three times a week for 8 weeks. The drug was administered at the 5th week of modeling. After 8 weeks， the mice were sacrificed， and serum and liver tissue samples were collected. The changes of body weight and death of mice were recorded. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST） and albumin （ALB） contents were detected after sampling. The degree of hepatic fibrosis was evaluated by sirius red collagen staining and liver hydroxyproline （Hyp） contents. The expression of platelet endothelial cell adhesion molecule-1 （CD31） and vascular endothelial growth factor receptor 2 （VEGFR2） protein in liver tissue were used to evaluate hepatic angiogenesis.,Results,2,The mortality rate of mice in the model group， Bushen Rougan Formula group and the Sorafenib group was 15.4%（2/13）， 0 and 7.7%（1/13）， respectively. The contents of serum ALT and AST in Bushen Rougan Formula group and the Sorafenib group were significantly decreased （,P,<,0.05）， while the content of serum ALB was significantly increased （,P,<,0.05）. Sirius red staining showed that the degree of fibrosis in Bushen Rougan Formula group and Sorafenib group was significantly reduced compared with the model group. Western blot and liver immunohistochemistry showed that CD31 and VEGFR2 protein expression were significantly down-regulated in Bushen Rougan Formula group and the Sorafenib group compared with the model group （,P,<,0.05）.,Conclusion,2,Bushen Rougan Formula can effectively improve DMN-induced hepatic fibrosis in mouse model， and its mechanism may be related to inhibition of angiogenesis.

关键词

补肾柔肝方二甲基亚硝胺肝纤维化血管新生

Keywords

Bushen Rougan Formuladimethylnitrosaminehepatic fibrosisangiogenesis

references

FORBES S J， GUPTA S，DHAWAN A. Cell therapy for liver disease： From liver transplantation to cell factory［J］. J Hepatol， 2015 ，62（1）： S157-S169.

YOSHIJI H， KURIYAMA S， YOSHII J， et al. Vascular endothelial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis［J］. Gut， 2003， 52（9）： 1347-1354.

NI Y， LI J M， LIU M K， et al. Pathological process of liver sinusoidal endothelial cells in liver diseases［J］. World J Gastroenterol， 2017， 23（43）： 7666-7677.

WANG Z， LI J， XIAO W， et al. The STAT3 inhibitor S3I-20 suppresses fibrogenesis and angiogenesis in liver fibrosis［J］. Lab Invest， 2018， 98（12）：1600-1613.

ELPEK G Ö. Angiogenesis and liver fibrosis［J］. World J Hepatol， 2015， 7（3）： 377-391.

LIU L， YOU Z， YU H， et al. Mechanotransduction-modulated fibrotic microniches reveal the contribution of angiogenesis in liver fibrosis［J］. Nat Mater， 2017， 16（12）： 1252-1261.

王见义，张美珠.补肾柔肝方治疗乙肝后肝纤维化临床对照研究［J］.辽宁中医药大学学报，2014， 16（6）： 118-120.

郑亚江，吴樱，洪蔚蔚，等. 补肾柔肝方对肝纤维化大鼠肝组织TGF-β1-Smads信号通路的干预作用［J］.现代中西医结合杂志，2018， 27（27）： 2965-2968.

金明姬，黄伟，陈卫，等.3种小鼠肝纤维化模型的比较及凯时注射液的抗肝纤维化作用评价［J］.解放军医学杂志，2013， 38（9）： 714-719.

冯劲立，沈海蓉，李想，等.防己黄芪汤对复合造模肝纤维化小鼠肝线粒体过氧化损伤的影响［J］.中药新药与临床药理，2010，21（5）：506-508.

张斌，王灵台.补肾柔肝方对二甲基亚硝胺诱导大鼠肝纤维化后CTGF mRNA表达的影响［J］. 世界华人消化杂志，2008（20）： 2224-2228.

LI S， DAI W， MO W， et al. By inhibiting PFKFB3， aspirin overcomes sorafenib resistance in hepatocellular carcinoma［J］. Int J Cancer， 2017， 141（12）： 2571-2584.

聂红明，王灵台. 安络化纤丸抗肝纤维化的研究进展［J］. 中西医结合肝病杂志，2016， 26（3）： 185-187.

吴惠春，张斌，王灵台. 柔肝方含药血清对TGF-β1诱导人肝星状细胞表达骨桥蛋白的影响及其机制［J］.中国实验方剂学杂志，2015， 21（13）： 109-113.

CORPECHOT C， BARBU V， WENDUM D， et al. Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis［J］. Hepatology， 2002， 35（5）： 1010-1021.

LEE J S， SEMELA D， IREDALE J， et al. Sinusoidal remodeling and angiogenesis： a new function for the liver-specific pericyte［J］. Hepatology， 2007， 45（3）： 817-825.

FERRARA N， GERBER H P， LECOUTER J. The biology of VEGF and its receptors［J］. Nat Med， 2003， 9（6）： 669-676.

YANG L， KWON J， POPOV Y， et al. Vascular endothelial growth factor promotes fibrosis resolution and repair in mice［J］. Gastroenterology， 2014， 146（5）： 1339-1350.

NAKAMURA I， ZAKHARIA K， BANINI B A， et al. Brivanib attenuates hepatic fibrosis in vivo and stellate cell activation in vitro by inhibition of FGF， VEGF and PDGF Signaling［J］. PLoS ONE， 2015， 9（4）： e0142355.

WOODFIN A， VOISIN MB， NOURSHARGH S. PECAM-1： a multi-functional molecule in inflammation and vascular biology［J］. Arterioscler Thromb Vasc Biol， 2007， 27（12）： 2292-2301.

吕靖，谭烨，赵志敏，等.扶正化瘀组分复方抑制血管新生的抗肝纤维化作用机制［J］.世界中医药，2015， 10（2）： 186-191.

ZHAO S， ZHANG Z， YAO Z， et al. Tetramethylpyrazine attenuates sinusoidal angiogenesis via inhibition of hedgehog signaling in liver fibrosis［J］. IUBMB Life， 2017， 69（2）： 115-127.

KANTARI-MIMOUN C， CASTELLS M， KLOSE R， et al. Resolution of liver fibrosis requires myeloid cell-driven sinusoidal angiogenesis［J］. Hepatology， 2015， 61（6）： 2042-2055.

陈兰羽，马继征，刘咏梅，等. 基于HIF-1α介导的VEGF mRNA表达探讨膈下逐瘀汤抗肝纤维化血管新生的机制［J］. 中草药，2019， 50（2）： 449-456.

高俪原，梁宝瑜，金春，等. 血管新生在肝脏疾病发生与发展中作用的研究进展［J］. 生理科学进展，2020， 51（3）： 193-197.

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