Neuroprotective effect of recombinant adeno-associated virus human thioredoxin-PR39 on acute cerebral infarction in rats

被引:9
作者
Guo, Yu-Dong [1 ]
Huang, Teng [2 ]
Sheng, Wen-Hua [3 ]
Guan, Yun-Fei [4 ]
Du, Yi-Feng [5 ]
Lin, You-Ting [5 ]
Ruan, Xi-Yun [5 ]
机构
[1] Fifth Peoples Hosp Jinan, Dept Neurol, Jinan 250022, Shandong, Peoples R China
[2] Shandong Univ, Shandong Prov Hosp, Dept Neurol, Jinan 250022, Shandong, Peoples R China
[3] Shandong Univ, Dept Neurol, Jinan Cent Hosp, Jinan 250013, Shandong, Peoples R China
[4] Shandong Univ, Sch Med, Dept Neurol, Jinan 250012, Shandong, Peoples R China
[5] Shandong Univ, Dept Neurol, Shandong Prov Hosp, 324 Jingwuweiqi Rd, Jinan 250021, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
adeno-associated virus; thioredoxin; PR39; gene fusion; gene therapy; acute cerebral infarction; ISCHEMIA-REPERFUSION INJURY; MEDIATED GENE-THERAPY; ANTIMICROBIAL PEPTIDE; ARTERY OCCLUSION; PR-39; STROKE; APOPTOSIS; PROLIFERATION; REGULATOR; BINDING;
D O I
10.3892/etm.2018.6456
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
The recombinant adeno-associated virus human thioredoxin-PR39 (rAAV/hTRX-PR39) has been demonstrated to have a protective effect on hypoxic cells. The present study aimed to explore the potential effect of rAAV/hTRX-PR39 on acute cerebral infarction in rats. Middle cerebral artery occlusion (MCAO) model rats were produced and divided into three groups: Normal saline group, empty virus group (rAAV, without hTRX-PR39 cDNA) and rAAV/hTRX-PR39 group. Hematoxylin and eosin staining and electron microscopy observation were used to assess the morphological changes of ischemic brain tissue during different periods. Immunohistochemistry was employed to detect the expression of CD34 to reflect angiogenesis of ischemic brain tissue. Rats treated with rAAV/hTRX-PR39 showed an alleviated degree of ischemic brain edema relative to that in control groups, suggesting PR39 can ameliorate brain damage after cerebral ischemia. In the rAAV/hTRX-PR39 group, CD34-positive cells were significantly increased in ischemic brain tissues compared to control groups. Furthermore, CD34-positive cells were primarily observed around the perivascular in ischemic brain, indicating the angiogenesis role of PR39 in ischemic brain. The present findings suggest that PR39 could effectively ameliorate ischemic brain damage and promote angiogenesis, which may contribute to the treatment of acute cerebral infarction.
引用
收藏
页码:2633 / 2638
页数:6
相关论文
共 32 条
[1]
Intramyocardial Injection of Recombinant Adeno-Associated Viral Vector Coexpressing PR39/Adrenomedullin Enhances Angiogenesis and Reduces Apoptosis in a Rat Myocardial Infarction Model [J].
An, Rui ;
Xi, Cong ;
Xu, Jian ;
Liu, Ying ;
Zhang, Shumiao ;
Wang, Yuemin ;
Hao, Yuewen ;
Sun, Lijun .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2017, 2017
[2]
Aoki Motokuni, 2006, Nihon Rinsho, V64, P762
[3]
PR-39 and PR-11 peptides inhibit ischemia-reperfusion injury by blocking proteasome-mediated IκBα degradation [J].
Bao, JL ;
Sato, K ;
Li, M ;
Gao, YH ;
Abid, R ;
Aird, W ;
Simons, M ;
Post, MJ .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2001, 281 (06) :H2612-H2618
[4]
RAT MIDDLE CEREBRAL-ARTERY OCCLUSION - EVALUATION OF THE MODEL AND DEVELOPMENT OF A NEUROLOGIC EXAMINATION [J].
BEDERSON, JB ;
PITTS, LH ;
TSUJI, M ;
NISHIMURA, MC ;
DAVIS, RL ;
BARTKOWSKI, H .
STROKE, 1986, 17 (03) :472-476
[5]
Monomeric recombinant peptide aptamers are required for efficient intracellular uptake and target inhibition [J].
Borghouts, Corina ;
Kunz, Christian ;
Delis, Natalia ;
Groner, Bernd .
MOLECULAR CANCER RESEARCH, 2008, 6 (02) :267-281
[6]
Acute treatment and long-term management of stroke in developing countries [J].
Brainin, Michael ;
Teuschl, Yvonne ;
Kalra, Lalit .
LANCET NEUROLOGY, 2007, 6 (06) :553-561
[7]
Role of HIF-1α or in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis [J].
Carmeliet, P ;
Dor, Y ;
Herbert, JM ;
Fukumura, D ;
Brusselmans, K ;
Dewerchin, M ;
Neeman, M ;
Bono, F ;
Abramovitch, R ;
Maxwell, P ;
Koch, CJ ;
Ratcliffe, P ;
Moons, L ;
Jain, RK ;
Collen, D ;
Keshet, E .
NATURE, 1998, 394 (6692) :485-490
[8]
PR-39, a syndecan-inducing antimicrobial peptide, binds and affects p130Cas [J].
Chan, YR ;
Gallo, RL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (44) :28978-28985
[9]
A next step in adeno-associated virus-mediated gene therapy for neurological diseases: regulation and targeting [J].
Chtarto, Abdelwahed ;
Bockstael, Olivier ;
Tshibangu, Terence ;
Dewitte, Olivier ;
Levivier, Marc ;
Tenenbaum, Liliane .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2013, 76 (02) :217-232
[10]
RETRACTED: Protection against myocardial ischemia-reperfusion injury by the angiogenic masterswitch protein PR 39 gene therapy: The roles of HIF1α stabilization and FGFR1 signaling (Retracted Article) [J].
De Muinck, Ebo D. ;
Nagy, Norbert ;
Tirziu, Daniela ;
Murakami, Masahiro ;
Gurusamy, Narasimman ;
Goswami, Shyamal K. ;
Ghatpande, Satish ;
Engelman, Richard M. ;
Simons, Michael ;
Das, Dipak K. .
ANTIOXIDANTS & REDOX SIGNALING, 2007, 9 (04) :437-445