您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (10): 16-20.doi: 10.6040/j.issn.1671-7554.0.2014.1000

• 基础医学 • 上一篇    下一篇

Caveolin-1对脑缺血大鼠血管新生的影响

郑娟1, 李政2, 张文静1, 袁琳冉1, 樊书菠1, 刘玉刚1, 袁中瑞1   

  1. 1. 山东大学医学院病理生理学教研室, 山东 济南 250012;
    2. 昆明医科大学第二附属医院, 云南 昆明 650101
  • 收稿日期:2014-12-26 出版日期:2015-10-10 发布日期:2015-10-10
  • 通讯作者: 刘玉刚。E-mail:liu.yugang@sdu.edu.cn;袁中瑞。E-mail:zhongruiyuan@sdu.edu.cn E-mail:liu.yugang@sdu.edu.cn;zhongruiyuan@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(81171106,81201391);中国博士后科学基金(20110491578)

Role of Caveolin-1 in postischemic angiogenesis in a rat model of ischemic stroke

ZHENG Juan1, LI Zheng2, ZHANG Wenjing1, YUAN Linran1, FAN Shubo1, LIU Yugang1, YUAN Zhongrui1   

  1. 1. Department of Pathophysiology, School of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. The Second Hospital of Kunming Medical University, Kunming 650101, Yunnan, China
  • Received:2014-12-26 Online:2015-10-10 Published:2015-10-10

PDF (PC)

296

摘要： 目的 探讨缺血性脑卒中大鼠缺血周边脑组织Caveolin-1(Cav-1)的表达及抑制其表达对缺血周边血管新生的影响。方法 随机将雄性Wistar大鼠分为4组:假手术组(Sham组,n=15),脑缺血组(MCAO组,n=55),Cav-1 siRNA慢病毒转染组(siRNA组,n=20)以及非编码siRNA慢病毒转染组(misRNA组,n=20)。用Q-PCR以及免疫印迹检测Cav-1的动态表达,FITC-dextran检测血管密度,多普勒血流仪检测血流量。结果 与Sham组比较,MCAO组再灌注4 h~3 d, Cav-1表达逐渐下降(P均<0.05),3 d表达水平最低(P<0.01),7 d 后明显恢复(P<0.05),14 d接近正常(P>0.05)。与MCAO组比较,siRNA组Cav-1的表达水平显著降低,并且缺血周边血管密度及血流量显著下降(P均<0.05);misRNA组的上述指标无明显变化。结论 Cav-1参与调节缺血性脑卒中后缺血周边脑组织的血管新生。

关键词: Caveolin-1, 血管新生, 大鼠, 缺血性脑卒中

Abstract: Objective To investigate the expression and involvement of Caveolin-1(Cav-1) in postischemic angiogenesis using a rat model of ischemic stroke. Methods Normal male Wistar rats were randomly divided into four groups: Sham group(n=15), cerebral ischemia group (MCAO group, n=55), lentivirus-expressing Cav-1 siRNA treated group (siRNA group, n=20) and lentivirus-expressing nonsense siRNA treated group (misRNA group, n=20). Q-PCR and Western blotting analysis were used to detect the expression of Cav-1. FITC-dextran was used to detect the vessel volume, and Laser Doppler was used to measure the local cerebral blood flow in ischemic penumbral. Results The expressions of Cav-1 from hour 4 to day 3 post-MCAO significantly decreased in MCAO group (all P<0.05), compared with sham group, and the minimum level appeared on day 3 post-MCAO(P<0.01). Interestingly, the expression of Cav-1 on day 7 post-MCAO significantly restored (P<0.05), and reached the normal level on day 14 post-MCAO(P>0.05). As expected, in Cav-1 siRNA group, the expression of Cav-1 significantly decreased compared with MCAO or misRNA group (all P<0.05). Meanwhile, there were significantly weakened vessel volume and local cerebral blood flow in ischemic penumbral (P<0.05). Conclusion Cav-1 might be involved in postischemic angiogenesis. Further investigation of the regulation molecular machenism of Cav-1 in postischemic angiogenesis may be helpful for therapeutic angiogenesis for ischemic stroke.

Key words: Rats, Angiogenesis, Ischemic stroke, Caveolin-1

中图分类号: 

  • R614.2
[1] Beck H, Plate KH. Angiogenesis after cerebral ischemia[J]. Acta Neuropathol, 2009, 117(5): 481-496.
[2] Li Y, Lu Z, Keogh CL, et al. Erythropoietin-induced neurovascular protection, angiogenesis, and cerebral blood flow restoration after focal ischemia in mice[J]. Cereb Blood Flow Metab, 2007, 27(5): 1043-1054.
[3] Sonveaux P, Martinive P, DeWever J, et al. Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlim collateralization and nitric oxide-mediated angiogenesis[J]. Circ Res, 2004, 95(2):154-161.
[4] 李慧, 黄景阳, 陈海丽, 等. 脑缺血再灌注后大鼠海马Wnt7b的表达[J]. 山东大学学报:医学版, 2013, 51(2): 7-11. LI Hui, HUANG Jingyang, CHEN Haili, et al. Expression and location of Wnt7b in rat subgranular zone of hippocampus dentate gyrus after cerebral ischemia-reperfusion[J]. Journal of Shandong University: Health Science, 2013, 51(2): 7-11.
[5] Bederson JB, Pitts LH, Tsuji M, et al. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic evaluation[J]. Stroke, 1986, 17(3):472-476.
[6] Liu S, Liu W, Ding W, et al. Electron paramagnetic resonance-guided normobaric hyperoxia treatment protects the brain by maintaining penumbral oxygenation in a rat model of transient focal cerebral ischemia[J]. J Cereb Blood Flow Metab, 2006, 26(10):1274-1284.
[7] Navarro A, Anand-Apte B, Parat MO. A role for caveolae in cell migration[J]. FASEB J, 2004, 18(15):1801-1811.
[8] Ghajar CM, Blevins KS, Hughes CC, et al. Mesenchymal stem cells enhance angiogenesis in mechanically viable prevascularized tissues via early matrix metalloproteinase upregulation[J]. Tissue Eng, 2006, 12(10):2875-2888.
[9] Sonveaux P, Martinive P, DeWever J, et al. Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis[J]. Circ Res, 2004, 95(2):154-161.
[10] Shatz M, Liscovitch M. Caveolin-1: a tumor-promoting role in human cancer[J]. Int J Radiat Biol, 2008, 84(3):177-189.
[11] Mehta D, Malik AB. Signaling mechanisms regulating endothelial permeability[J]. Physiol Rev, 2006, 86(1):279-367.
[12] Razani B, Engelman JA, Wang XB, et al. Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities[J]. J Biol Chem, 2001, 276(41):38121-38138.
[13] Sonveaux P, Martinive P, DeWever J, et al. Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis[J]. Circ Res, 2004, 95(2):154-161.
[14] Liu J, Wang XB, Park DS, et al. Caveolin-1 expression enhances endothelial capillary tubule formation[J]. J Biol Chem, 2002, 277(12):10661-10668.
[15] Rosenstein JM, Krum JM. New roles for VEGF in nervous tissue-beyond blood vessels[J]. Exp Neurol, 2004, 187(2):246-253.
[16] Zhang R, Wang L, Zhang L, et al. Nitric oxide enhances angiogenesis via the synthesis of vascular endo thelial grow the factor and cGM P after stroke in the rat[J]. Circ Res, 2003, 92(3):308-313.
[1] 吴逸南 葛志明 李方 贺红 姜虹 张运. 自发性高血压大鼠肾脏血管紧张素转换酶2的表达[J]. 山东大学学报(医学版), 2209, 47(6): 5-.
[2] 祝林 胡三元 张光永 丁祥就. 前列腺素E2对阻塞性黄疸大鼠小肠粘膜形态的保护作用[J]. 山东大学学报(医学版), 2209, 47(6): 12-.
[3] 孙涛 张道来 谢珊珊 王玉卓 冯玉新 辛华. 酒精对原代培养的神经前体细胞间隙连接蛋白43表达的影响[J]. 山东大学学报(医学版), 2209, 47(6): 20-.
[4] 张道来 孙涛 谢珊珊 王玉卓 赵玲 冯玉新 辛华. 体外原代培养胎鼠大脑皮层神经元NMDAR1亚基表达的发育性变化[J]. 山东大学学报(医学版), 2209, 47(6): 28-32.
[5] 张亮,徐敏,庄向华,娄福臣,娄能俊,吕丽,郭文娟,郑凤杰,陈诗鸿. 内质网应激与凋亡在糖尿病周围神经病变中的表达变化[J]. 山东大学学报（医学版）, 2017, 55(8): 13-17.
[6] 刘芳,乔蕾,陈文超,杨丽娜. 大蒜素后处理对大鼠心肌缺血-再灌注损伤的保护作用[J]. 山东大学学报（医学版）, 2017, 55(7): 6-11.
[7] 谢海滨,武群政,刘少壮,黄鑫,程玉刚,胡三元,张光永. 肝线粒体相关内质网膜在袖状胃切除术改善糖尿病大鼠胰岛素敏感性中的作用[J]. 山东大学学报（医学版）, 2017, 55(10): 36-40.
[8] 陈怡憓,刘学蔚,侯绪浩,孙钦峰. 醛化白及多糖/羟丙基壳聚糖/纳米珍珠层粉复合材料促下颌骨缺损修复的动物实验研究[J]. 山东大学学报（医学版）, 2016, 54(6): 7-11.
[9] 李红志,刘静,宋岩,迟令懿,刘玉光. 利拉鲁肽对脊髓损伤修复作用的探讨[J]. 山东大学学报（医学版）, 2016, 54(4): 1-5.
[10] 曲立新,时兴华,杜怡峰. 急性缺血性脑卒中患者血浆PMP及EMP含量与预后的相关性[J]. 山东大学学报（医学版）, 2016, 54(12): 32-36.
[11] 任宝鑫,马云峰,刘殿伟,李卓,姜勇. Wnt3a在大鼠蛛网膜下腔出血后早期脑损伤中对神经细胞自噬和凋亡的影响[J]. 山东大学学报（医学版）, 2016, 54(10): 11-15.
[12] 赵蕙琛,柴家超,张亮,袁明振,彭力,刘元涛. 糖尿病大鼠阴茎海绵体硫化氢含量及其合成酶表达的变化[J]. 山东大学学报（医学版）, 2016, 54(10): 25-28.
[13] 陈志新,王颖,曹新冉, 黑乃豪,李俊龙,董波,关广聚. 非肽类Ang(1-7)受体激动剂AVE0991对大鼠糖尿病肾病的保护作用[J]. 山东大学学报（医学版）, 2016, 54(10): 29-33.
[14] 张东青, 王勇, 陈守臻, 朱耀丰, 史本康. 糖尿病大鼠尿道α1肾上腺素能受体与神经生长因子表达的改变及其对尿道功能的影响[J]. 山东大学学报（医学版）, 2015, 53(9): 30-34.
[15] 冯潇雨, 张洪美, 车选强, 康东红. 成骨细胞刺激因子对去卵巢骨质疏松大鼠的治疗效果[J]. 山东大学学报（医学版）, 2015, 53(7): 8-12.
Viewed
Full text
233
HTML PDF
Just accepted Online first Issue Just accepted Online first Issue
0 0 0 0 0 233

  From Others local
  Times 30 203
  Rate 13% 87%

Abstract
933
Just accepted Online first Issue
0 0 933
  From Others
  Times 933
  Rate 100%

Cited
Web of Science  Crossref   ScienceDirect  Search for Citations in Google Scholar >>
 
This page requires you have already subscribed to WoS.
  Shared   
  Discussed   
No Suggested Reading articles found!
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发