高级检索
中华实验眼科杂志
期刊首页
过刊列表
高级检索
稿件发表
• 实验研究 •
ENGLISH ABSTRACT
芪灯明目胶囊对氧诱导视网膜病变小鼠视网膜血管的保护作用
刘春梦
丁珊
董雪雯
赵丹丹
蒲思源
裴利
张富文
作者及单位信息
·
DOI： 10.3760/cma.j.cn115989-20220426-00181
Protective effect of Qideng Mingmu capsule on retinal vessels in mice with oxygen-induced retinopathy
Liu Chunmeng
Ding Shan
Dong Xuewen
Zhao Dandan
Pu Siyuan
Pei Li
Zhang Fuwen
Authors Info & Affiliations
Liu Chunmeng
Eye School of Chengdu University of Traditional Chinese Medicine, Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection, Chengdu 610075, China
Ding Shan
Eye School of Chengdu University of Traditional Chinese Medicine, Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection, Chengdu 610075, China
Dong Xuewen
Eye School of Chengdu University of Traditional Chinese Medicine, Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection, Chengdu 610075, China
Zhao Dandan
Eye School of Chengdu University of Traditional Chinese Medicine, Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection, Chengdu 610075, China
Pu Siyuan
Eye School of Chengdu University of Traditional Chinese Medicine, Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection, Chengdu 610075, China
Pei Li
Eye School of Chengdu University of Traditional Chinese Medicine, Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection, Chengdu 610075, China
Zhang Fuwen
Eye School of Chengdu University of Traditional Chinese Medicine, Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection, Chengdu 610075, China
·
DOI： 10.3760/cma.j.cn115989-20220426-00181
0
0
0
0
0
0
PDF下载
APP内阅读
摘要

目的研究芪灯明目胶囊对氧诱导视网膜病变(OIR)小鼠视网膜新生血管形成及重塑的影响。

方法将36只出生后第7天的(P7)SPF级C57BL/6J幼鼠采用随机数字表法分为正常组、OIR组、芪灯明目胶囊组和阿帕替尼组，每组9只。正常组小鼠于正常环境下饲养，其余小鼠均在高氧环境中[氧浓度为(75±2)%]饲养5 d(P7～P12)后再在正常环境中饲养5 d(P12～P17)建立OIR模型。芪灯明目胶囊组和阿帕替尼组从P12开始分别给予芪灯明目胶囊(900 mg/kg)与血管内皮生长因子受体2抑制剂阿帕替尼(70 mg/kg)灌胃，1次/d，连续5 d。P17时，摘取小鼠眼球，制作眼球石蜡切片并行苏木精－伊红染色，计数各组小鼠突破内界膜的血管内皮细胞数目；制作视网膜铺片并行FITC-dextran荧光染色，计算视网膜无灌注区面积比、新生血管密度与总血管密度；采用免疫荧光染色法检测视网膜血管内皮细胞标志物CD31与周细胞标志物α-平滑肌肌动蛋白(α-SMA)的分布和荧光强度；采用免疫组织化学染色法检测视网膜缺氧诱导因子1α(HIF-1α)与血管内皮钙黏蛋白(VE-cadherin)的表达分布。

结果正常组、OIR组、芪灯明目胶囊组和阿帕替尼组突破内界膜的血管内皮细胞数目分别为(2.83±4.40)、(37.33±5.43)、(23.83±6.79)和(14.00±9.34)个，总体比较差异有统计学意义( F＝28.313， P<0.001)，其中OIR组突破内界膜血管内皮细胞数明显多于正常组、芪灯明目胶囊组和阿帕替尼组，差异均有统计学意义(均 P<0.05)。视网膜铺片结果显示，OIR组视网膜存在大片无灌注区域与新生血管芽，血管迂曲，分布紊乱，芪灯明目胶囊组和阿帕替尼组血管分布较OIR组更均匀，无灌注区面积和新生血管较OIR组减少。正常组、芪灯明目胶囊组和阿帕替尼组视网膜无灌注区面积比和新生血管密度均较OIR组降低，差异均有统计学意义(均 P<0.05)。正常组、芪灯明目胶囊组和阿帕替尼组CD31免疫荧光强度和HIF-1α吸光度值明显低于OIR组，α-SMA免疫荧光强度和VE-cadherin吸光度值明显高于OIR组，差异均有统计学意义(均 P<0.05)。

结论芪灯明目胶囊能够抑制OIR小鼠视网膜新生血管形成，增加血管周细胞覆盖，缓解视网膜缺氧以及增加血管完整性，对OIR小鼠视网膜血管起到保护作用。

视网膜新生血管;氧诱导视网膜病变;小鼠;芪灯明目胶囊;阿帕替尼
ABSTRACT

ObjectiveTo investigate the effect of Qideng Mingmu capsule on the formation and remodeling of retinal neovascularization in mice with oxygen-induced retinopathy (OIR).

MethodsThirty-six postnatal day 7 (P7)SPF grade C57BL/6J pups were divided into normal group, OIR group, Qideng Mingmu capsule group and apatinib group by random number table method, with 9 mice in each group.The mice in the normal group were raised in normal environment.The mice in the other three groups were fed in hyperoxic environment of (75±2)% oxygen concentration for 5 days from P7 to P12 and then were fed in normal environment for 5 days from P12 to P17 to establish the OIR model.From P12, mice in Qideng Mingmu capsule group and apatinib group were given intragastric administration of Qideng Mingmu capsule (900 mg/kg) and vascular endothelial growth factor receptor 2 inhibitor apatinib (70 mg/kg) respectively, once a day for 5 consecutive days.On P17, paraffin sections of mouse eyeballs were made and stained with hematoxylin-eosin to count the number of vascular endothelial cells that broke through the internal limiting membrane.The retinal slices were prepared and stained with FITC-dextran to quantify the retinal non-perfusion area, neovascularization density and total vascular density.The distribution and fluorescence intensity of retinal vascular endothelial cell marker CD31 and pericyte marker α-smooth muscle actin (α-SMA) were observed by double immunofluorescence staining.Immunohistochemical staining was used to detect the expression and distribution of retinal hypoxia inducible factor-1α (HIF-1α) and vascular endothelial cadherin (VE-cadherin).The use and care of animals were in accordance with the Regulations on the Management of Laboratory Animals issued by the Ministry of Science and Technology.This study was approved by the Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine (No.2019-30).

ResultsThe number of vascular endothelial cells breaking through the internal limiting membrane in normal group, OIR group, Qideng Mingmu capsule group and apatinib group were (2.83±4.40), (37.33±5.43), (23.83±6.79) and (14.00±9.34), respectively, with a statistically significant overall difference ( F=28.313, P<0.001).There were more vascular endothelial cells breaking through internal limiting membrane in OIR group than in normal group, Qideng Mingmu capsule group and apatinib group, showing statistically significant differences (all at P<0.05).In the observation of mouse retinal slices, there were large non-perfusion areas, neovascularization buds and disordered distribution of blood vessels in OIR group.The distribution of blood vessels was more uniform and the areas of non-perfusion and neovascularization were smaller in Qideng Mingmu capsule group and apatinib group than in OIR group.The relative area of central retinal non-perfusion area and neovascularization density were significantly lower in normal group, Qideng Mingmu capsule group and apatinib group than in OIR group (all at P<0.05).The immunofluorescence intensity of CD31 and the absorbance value of HIF-1α were significantly lower, and the immunofluorescence intensity of α-SMA and the absorbance value of VE-cadherin were significantly higher in normal group, Qideng Mingmu capsule group and apatinib group than in OIR group (all at P<0.05).

ConclusionsQideng Mingmu capsule can inhibit retinal neovascularization formation, increase vascular pericyte coverage, relieve retinal hypoxia and increase vascular integrity in OIR mice.It can protect the retinal vessels of OIR mice.

Retinal neovascularization;Oxygen-induced retinopathy;Mouse;Qideng Mingmu capsule;Apatinib
Zhang Fuwen, Email: mocdef.3ab61333newfz
Copyright by Chinese Medical Association
No content published by the journals of Chinese Medical Association may be reproduced or abridged without authorization. Please do not use or copy the layout and design of the journals without permission.
All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.
引用本文

刘春梦,丁珊,董雪雯,等. 芪灯明目胶囊对氧诱导视网膜病变小鼠视网膜血管的保护作用[J]. 中华实验眼科杂志,2024,42(05)：428-435.

DOI:10.3760/cma.j.cn115989-20220426-00181

PERMISSIONS

Request permissions for this article from CCC.

评价本文
*以上评分为匿名评价

版权归中华医学会所有。

未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。

除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。

视网膜新生血管(retinal neovascularization，RNV)是早产儿视网膜病变、视网膜静脉阻塞和糖尿病视网膜病变等眼病的重要病理表现，常引起出血和渗漏，影响视功能 [ 1 , 2 ]。抗血管内皮生长因子(vascular endothelial growth factor，VEGF)玻璃体腔注射是目前RNV的标准药物治疗方式，可有效减轻黄斑水肿、减少新生血管以及改善或稳定视力 [ 3 ]。然而，VEGF抑制剂的视力改善作用通常会随着时间的推移而下降，需要频繁注射以维持视力，给患者和社会带来沉重的负担，且患者的依从性会随病程的延长而下降 [ 4 , 5 ]。也有研究表明抗VEGF治疗会加速增生性视网膜外膜的形成，并加剧玻璃体视网膜牵引 [ 6 ]。因此，有必要研究RNV新的治疗方法。芪灯明目胶囊由葛根、黄芪和灯盏细辛组成。有研究显示芪灯明目胶囊能减轻高血糖导致的大鼠视网膜微血管损害，减少周细胞丢失，保护血－视网膜屏障，其作用机制可能与抑制VEGF-A，以及缺氧诱导因子1α(hypoxia inducible factor-1α，HIF-1α)等有关 [ 7 , 8 , 9 , 10 ]。葛根素能抑制氧诱导的大鼠RNV，黄芪能减少高糖环境下血管内皮细胞损伤，灯盏细辛能使癌变组织的血管向良性血管生长，从而产生"良性血管生成"的抗癌功效 [ 11 , 12 , 13 ]。基于以上研究，推测芪灯明目胶囊能抑制RNV的形成，并且可能对新生血管具有良性血管转化作用，从而促进视网膜血管系统稳定。由于芪灯明目胶囊是口服给药，而目前针对RNV标准的治疗是抗VEGF药物玻璃体注射治疗。为避免给药方式产生的影响，本研究以口服VEGFR2抑制剂阿帕替尼 [ 14 ]作为阳性对照药物。本研究建立氧诱导视网膜病变(oxygen-induced retinopathy，OIR)模型，观察芪灯明目胶囊对RNV形成和重塑的影响，探讨芪灯明目胶囊是否在抑制RNV形成的同时促进良性血管转化，从而保护视网膜，为其临床应用提供新的实验依据。
试读结束，您可以通过登录机构账户或个人账户后获取全文阅读权限。
参考文献
[1]
Carmeliet P ， Jain RK . Molecular mechanisms and clinical applications of angiogenesis[J]. Nature， 2011，473(7347)∶298－307. DOI： 10.1038/nature10144 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Potente M ， Gerhardt H ， Carmeliet P ．Basic and therapeutic aspects of angiogenesis[J]. Cell， 2011，146(6)∶873－887. DOI： 10.1016/j.cell.2011.08.039 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Ferrara N ， Adamis AP . Ten years of anti-vascular endothelial growth factor therapy[J]. Nat Rev Drug Discov， 2016，15(6)∶385－403. DOI： 10.1038/nrd.2015.17 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Ciulla TA ， Huang F ， Westby K ，et al. Real-world outcomes of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration in the United States[J]. Ophthalmol Retina， 2018，2(7)∶645－653. DOI： 10.1016/j.oret.2018.01.006 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Wecker T ， Ehlken C ， Bühler A ，et al. Five-year visual acuity outcomes and injection patterns in patients with pro-re-nata treatments for AMD，DME，RVO and myopic CNV[J]. Br J Ophthalmol， 2017，101(3)∶353－359. DOI： 10.1136/bjophthalmol-2016-308668 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Avery RL . Bevacizumab (Avastin) for retinopathy of prematurity：wrong dose，wrong drug，or both？[J]. J AAPOS， 2012，16(1)∶2－4. DOI： 10.1016/j.jaapos.2011.11.002 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Zhang M ， Yang J ， Zhao X ，et al. Network pharmacology and molecular docking study on the active ingredients of qidengmingmu capsule for the treatment of diabetic retinopathy[J/OL]. Sci Rep， 2021，11(1)∶7382[2023－06－16]. http://www.ncbi.nlm.nih.gov/pubmed/33795817. DOI： 10.1038/s41598-021-86914-8 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
李强，段俊国，王红义，等．芪灯明目胶囊对自发性糖尿病大鼠视网膜蛋白激酶C表达的影响[J]. 眼科新进展， 2010，30(3)∶210－213.
返回引文位置Google Scholar
百度学术
万方数据
Li Q ， Duan JG ， Wang HY ，et al. Effect of Qidengmingmu capsule on protein kinase C in retina of spontaneous diabetic rats[J]. Rec Adv Ophthalmol， 2010，30(3)∶210－213.
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[9]
黄贵芝，段俊国，杨灵萍，等．中药部位复方DGH对STZ诱发的糖尿病大鼠早期视网膜形态学影响的实验研究[J]. 中国中医眼科杂志， 2008，18(4)∶204－206＋184.
返回引文位置Google Scholar
百度学术
万方数据
Huang GZ ， Duan JG ， Yang LP ，et al. Effect of DGH on retinal morphology impairment of STZ DM rats[J]. J Tradit Chin Ophthalmol， 2008，18(4)∶204－206＋184.
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[10]
张富文，段俊国，赵凌，等．芪灯明目胶囊对高血糖大鼠血视网膜屏障影响的研究[J]. 国际眼科杂志， 2013，13(6)∶1077－1080. DOI： 10.3980/j.issn.1672-5123.2013.06.04 .
返回引文位置Google Scholar
百度学术
万方数据
Zhang FW ， Duan JG ， Zhao L ，et al. Effect of Chinese medicine Qidengmingmu capsule on the STZ induced hyperglycemia rat's blood-retinal barrier[J]. Int Eye Sci， 2013，13(6)∶1077－1080. DOI： 10.3980/j.issn.1672-5123.2013.06.04 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[11]
岑璐莎．葛根素对氧诱导大鼠视网膜新生血管模型PECAM-1及VEGF表达的影响[J]. 浙江中西医结合杂志， 2017，27(10)∶850－852＋916. DOI： 10.3969/j.issn.1005-4561.2017.10.007 .
返回引文位置Google Scholar
百度学术
万方数据
Cen LS . Effect of Puerarin on the expression of PECAM-1 and VEGF in hyperoxia-induced retinopathy of rats[J]. Zhejiang J Integr Tradit Chin West Med， 2017，27(10)∶850－852＋916. DOI： 10.3969/j.issn.1005-4561.2017.10.007 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[12]
彭军，郑一瑾，姜丹．黄芪注射液对高糖所致血管内皮细胞损伤的保护作用[J]. 中国现代医学杂志， 2007，17(17)∶2092－2095. DOI： 10.3969/j.issn.1005-8982.2007.17.012 .
返回引文位置Google Scholar
百度学术
万方数据
Peng J ， Zheng YJ ， Jiang D ．Protect effects of astragalus on traumatic vascular endothelial cells as a result of high glucose[J]. Chin J Modern Med， 2007，17(17)∶2092－2095. DOI： 10.3969/j.issn.1005-8982.2007.17.012 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[13]
周曾同，张水龙，华丽，等．灯盏细辛抗白斑癌变的功效及其血管生成机制的实验研究[J]. 中华口腔医学杂志， 2001，36(2)∶149－151. DOI： 10.3760/j.issn:1002-0098.2001.02.022 .
返回引文位置Google Scholar
百度学术
万方数据
Zhou ZT ， Zhang SL ， Hua L ，et al. Study of resisting leukoplakia canceration and angiopoiesis by herba erigerontis[J]. Chin J Stomatol， 2001，36(2)∶149－151. DOI： 10.3760/j.issn:1002-0098.2001.02.022 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[14]
Liu M ， Li H ， Wang X ，et al. Experimental study of the vascular normalization window for tumors treated with apatinib and the efficacy of sequential chemotherapy with apatinib in lung cancer-bearing mice and patients[J]. Cancer Med， 2020，9(8)∶2660－2673. DOI： 10.1002/cam4.2923 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Smith LE ， Wesolowski E ， McLellan A ，et al. Oxygen-induced retinopathy in the mouse[J]. Invest Ophthalmol Vis Sci， 1994，35(1)∶101－111.
返回引文位置Google Scholar
百度学术
万方数据
[16]
温臣婷，贺涛，邢怡桥．EPO加重氧诱导视网膜病变小鼠视网膜新生血管的形成[J]. 湖北医药学院学报， 2015，34(2)∶114－119＋104. DOI： 10.13819/j.issn.1006-9674.2015.02.002 .
返回引文位置Google Scholar
百度学术
万方数据
Wen CT ， He T ， Xing YQ . The erythropoietin aggratates the retinal neovascularization in retinopathic mice induced with oxygen[J]. J Hubei Univ Med， 2015，34(2)∶114－119＋104. DOI： 10.13819/j.issn.1006-9674.2015.02.002 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[17]
张艳，胡樱凡，杨巧巧，等．芪灯明目胶囊及有效组分对糖尿病视网膜病变大鼠的影响及机制研究[J]. 中药药理与临床， 2015，31(4)∶166－170.
返回引文位置Google Scholar
百度学术
万方数据
Zhang Y ， Hu YF ， Yang QQ ，et al. Protective effect and mechanism of Qidengmingmu capsule on diabetic retinopathy rats induced by streptozotocin[J]. Pharm Clin Chin Materia Medica， 2015，31(4)∶166－170.
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[18]
周曾同，金芝贵，张水龙，等．灯盏细辛对金地鼠颊囊癌血管生成影响的形态特征研究[J]. 临床口腔医学杂志， 2000，16(3)∶166－169. DOI： 10.3969/j.issn.1003-1634.2000.03.016 .
返回引文位置Google Scholar
百度学术
万方数据
Zhou ZT ， Jin ZG ， Zhang SL ，et al. A morphic study on erigeron breviscapus (Vant) Hand-Mazz affecting angiogenesis of golden hamster cheek pouch[J]. J Clin Stomatol， 2000，16(3)∶166－169. DOI： 10.3969/j.issn.1003-1634.2000.03.016 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[19]
周曾同，张水龙，丁瑞宇，等．灯盏细辛干预金地鼠颊囊癌变过程的α-SMA动态观察[J]. 上海口腔医学， 2000，9(2)∶107－109. DOI： 10.3969/j.issn.1006-7248.2000.02.016 .
返回引文位置Google Scholar
百度学术
万方数据
Zhou ZT ， Zhang SL ， Ding RY ，et al. Observation on α-SMA during erigeron breviscapus(Vant) Hand-Mazz obstructs the evolution of carcinogenesis of gloden hamster cheek pouch[J]. Shanghai J Stomatol， 2000，9(2)∶107－109. DOI： 10.3969/j.issn.1006-7248.2000.02.016 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[20]
李雯霖，姜德咏，郭丽花，等．葛根素抑制缺氧状态下人视网膜色素上皮细胞低氧诱导因子-1α表达[J]. 眼科新进展， 2006，26(7)∶504－507. DOI： 10.3969/j.issn.1003-5141.2006.07.007 .
返回引文位置Google Scholar
百度学术
万方数据
Li WL ， Jiang DY ， Guo LH ，et al. Inhibition of puerarin on the expression of hypoxia-inducible factor-1α in human RPE cells in hypoxic condition[J]. Rec Adv Ophthalmol， 2006，26(7)∶504－507. DOI： 10.3969/j.issn.1003-5141.2006.07.007 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[21]
陶文迪，田秀玉，李茂星，等．黄芪水提取物对高原缺氧大鼠运动能力的影响[J]. 解放军医药杂志， 2019，31(12)∶12－18. DOI： 10.3969/j.issn.2095-140X.2019.12.003 .
返回引文位置Google Scholar
百度学术
万方数据
Tao WD ， Tian XY ， Li MX ，et al. Effect of astragalus membranaceus aqueous extract on ability of plateau hypoxia exercise in rats[J]. Med Pharm J Chin PLA， 2019，31(12)∶12－18. DOI： 10.3969/j.issn.2095-140X.2019.12.003 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[22]
卢飞艳，丁燕子，陈相健，等．黄芪甲苷促进缺氧损伤后人主动脉内皮细胞血管新生的研究[J]. 南京医科大学学报(自然科学版)， 2019，39(8)∶1124－1129. DOI： 10.7655/NYDXBNS20190806 .
返回引文位置Google Scholar
百度学术
万方数据
Lu FY ， Ding YZ ， Chen XJ ，et al. Astragaloside Ⅳ promoted angiogenesis of human aortic endothelial cells after hypoxic injury[J]. J Nanjing Med Univ (Natural Sci)， 2019，39(8)∶1124－1129. DOI： 10.7655/NYDXBNS20190806 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[23]
Jain RK . Normalizing tumor vasculature with anti-angiogenic therapy：a new paradigm for combination therapy[J]. Nat Med， 2001，7(9)∶987－989. DOI： 10.1038/nm0901-987 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Goel S ， Duda DG ， Xu L ，et al. Normalization of the vasculature for treatment of cancer and other diseases[J]. Physiol Rev， 2011，91(3)∶1071－1121. DOI： 10.1152/physrev.00038.2010 .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Shepro D ， Morel NM . Pericyte physiology[J]. FASEB J， 1993，7(11)∶1031－1038. DOI： 10.1096/fasebj.7.11.8370472 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Li Z ， Ning F ， Wang C ，et al. Normalization of the tumor microvasculature based on targeting and modulation of the tumor microenvironment[J/OL]. Nanoscale， 2021，13(41)∶17254－17271[2023－08－18]. http://www.ncbi.nlm.nih.gov/pubmed/34651623. DOI： 10.1039/d1nr03387e .
返回引文位置Google Scholar
百度学术
万方数据
[27]
Gunaratnam L ， Bonventre JV . HIF in kidney disease and development[J]. J Am Soc Nephrol， 2009，20(9)∶1877－1887. DOI： 10.1681/ASN.2008070804 .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Kaur B ， Khwaja FW ， Severson EA ，et al. Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis[J]. Neuro Oncol， 2005，7(2)∶134－153. DOI： 10.1215/S1152851704001115 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
Taveau JC ， Dubois M ， Le Bihan O ，et al. Structure of artificial and natural VE-cadherin-based adherens junctions[J]. Biochem Soc Trans， 2008，36(Pt 2)∶189－193. DOI： 10.1042/BST0360189 .
返回引文位置Google Scholar
百度学术
万方数据
[30]
Vestweber D . VE-cadherin：the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation[J]. Arterioscler Thromb Vasc Biol， 2008，28(2)∶223－232. DOI： 10.1161/ATVBAHA.107.158014 .
返回引文位置Google Scholar
百度学术
万方数据
[31]
Dejana E ， Tournier-Lasserve E ， Weinstein BM . The control of vascular integrity by endothelial cell junctions：molecular basis and pathological implications[J]. Dev Cell， 2009，16(2)∶209－221. DOI： 10.1016/j.devcel.2009.01.004 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
张富文，Email： mocdef.3ab61333newfz
B

刘春梦：参与设计实验、研究实施、数据采集、分析/解释数据、统计分析及论文撰写；丁珊：参与设计实验、研究实施、数据采集及分析/解释数据；董雪雯：参与研究实施、数据采集及分析/解释数据；赵丹丹、蒲思源、裴利：参与数据采集和分析/解释数据；张富文：参与设计实验、研究实施、统计分析和论文智力性内容的修改及定稿

C
所有作者均声明不存在利益冲突
D
四川省自然科学基金面上项目 (2023NSFSC0690)
成都中医药大学"杏林学者"学科人才项目 (YXRC2018013)
评论 （0条）
注册
登录
时间排序
暂无评论，发表第一条评论抢沙发
最新推荐
更多
HIF-1α调控的巨噬细胞极化在免疫相关疾病中作用的研究进展
唐梦燕 等
国际免疫学杂志 2023,46(05)
外泌体miRNA在肿瘤进展中的作用及其可能机制
武伦 等
中华肝脏病杂志 2021,29(09)
膝关节周围滑囊及其相关疾病的MRI表现
叶琴 等
中华放射学杂志 2021,55(04)
中性粒细胞胞外诱捕网产生的分子机制及其在相关疾病中的作用
王迪 等
中华微生物学和免疫学杂志 2021,41(01)
MedAI助手（体验版）
文档即答
智问智答
机器翻译
回答内容由人工智能生成，我社无法保证其准确性和完整性，该生成内容不代表我们的态度或观点，仅供参考。
生成快照
文献快照

你好，我可以帮助您更好的了解本文，请向我提问您关注的问题。

0/2000

《中华医学会杂志社用户协议》 | 《隐私政策》

《SparkDesk 用户协议》 | 《SparkDesk 隐私政策》

网信算备340104764864601230055号 | 网信算备340104726288401230013号

技术支持：

历史对话
本文全部
还没有聊天记录
设置
模式
纯净模式沉浸模式
字号
小中大