Morroniside protects against cerebral ischemia/reperfusion injury by inhibiting neuron apoptosis and MMP2/9 expression

被引:44
作者
Zeng, Guoyong [1 ]
Ding, Weijiang [2 ]
Li, Yin [2 ]
Sun, Meiying [3 ]
Deng, Liying [2 ]
机构
[1] Nanchang Univ, Affiliated Ganzhou Hosp, Dept Neurol, Ganzhou 341000, Jiangxi, Peoples R China
[2] Nanchang Univ, Affiliated Hosp 2, Dept Neurol, 1 Minde Rd, Nanchang 330006, Jiangxi, Peoples R China
[3] Peoples Hosp Fuzhou, Dept Neurol, Fuzhou 344000, Jiangxi, Peoples R China
关键词
morroniside; cerebral ischemia; reperfusion injury; matrix metalloproteinase-2; matrix metalloproteinase-9; ISCHEMIA-REPERFUSION INJURY; BLOOD-BRAIN-BARRIER; CORNI FRUCTUS; UP-REGULATION; RATS; MATRIX; CELLS; CONTRIBUTES; DISRUPTION; ACTIVATION;
D O I
10.3892/etm.2018.6457
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The aim of the present study was to investigate the effect of morroniside against matrix metalloproteinase (MMP)2/9 and focal cerebral ischemia/reperfusion (I/R) injury in rats. A rat model of focal cerebral I/R injury rats was established and rats were administered with 30, 90 or 270 mg/kg/day morroniside for 7 days. The expression of MMP2/9 and neuronal apoptosis were assessed. In addition, the expression of active caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were measured. The results revealed that MMP2 and MMP9 expression was upregulated and the percentage of apoptotic neurons was increased in rats with focal cerebral I/R injury compared with the control. However, treatment with morroniside significantly inhibited I/R-induced MMP2/9 expression and neuron apoptosis compared with the untreated I/R injury group. Morroniside administration also decreased the expression of active caspase-3 and increased the Bcl-2/Bax ratio compared with untreated rats with focal cerebral I/R injury. The inhibitory effect of morroniside on MMP2/9 expression and neuron apoptosis was dose dependent. In summary, the results of the present study suggest that morroniside is able to protect against cerebral I/R injury in the brain and may have potential as a therapeutic treatment for patients who have suffered a stroke.
引用
收藏
页码:2229 / 2234
页数:6
相关论文
共 30 条
[1]   Guhong injection protects against focal cerebral ischemia-reperfusion injury via anti-inflammatory effects in rats [J].
Ai, Jinchao ;
Wan, Haitong ;
Shu, Mingchun ;
Zhou, Huifen ;
Zhao, Tao ;
Fu, Wei ;
He, Yu .
ARCHIVES OF PHARMACAL RESEARCH, 2017, 40 (05) :610-622
[2]   Matrix metalloproteinase 2 gene knockout has no effect on acute brain injury after focal ischemia [J].
Asahi, M ;
Sumii, T ;
Fini, ME ;
Itohara, S ;
Lo, EH .
NEUROREPORT, 2001, 12 (13) :3003-3007
[3]   Hydroxysafflor Yellow A Protects Against Cerebral Ischemia-Reperfusion Injury by Anti-apoptotic Effect Through PI3K/Akt/GSK3β Pathway in Rat [J].
Chen, Lin ;
Xiang, Yanxiao ;
Kong, Lingjun ;
Zhang, Xiumei ;
Sun, Baozhu ;
Wei, Xinbing ;
Liu, Huiqing .
NEUROCHEMICAL RESEARCH, 2013, 38 (11) :2268-2275
[4]   Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart [J].
Cheung, PY ;
Sawicki, G ;
Wozniak, M ;
Wang, WJ ;
Radomski, MW ;
Schulz, R .
CIRCULATION, 2000, 101 (15) :1833-1839
[5]   Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010 [J].
Feigin, Valery L. ;
Forouzanfar, Mohammad H. ;
Krishnamurthi, Rita ;
Mensah, George A. ;
Connor, Myles ;
Bennett, Derrick A. ;
Moran, Andrew E. ;
Sacco, Ralph L. ;
Anderson, Laurie ;
Truelsen, Thomas ;
O'Donnell, Martin ;
Venketasubramanian, Narayanaswamy ;
Barker-Collo, Suzanne ;
Lawes, Carlene M. M. ;
Wang, Wenzhi ;
Shinohara, Yukito ;
Witt, Emma ;
Ezzati, Majid ;
Naghavi, Mohsen ;
Murray, Christopher .
LANCET, 2014, 383 (9913) :245-255
[6]   Metalloproteinase-9 deficiency protects against hepatic ischemia/reperfusion injury [J].
Hamada, Takashi ;
Fondevila, Constantino ;
Busuttil, Ronald W. ;
Coito, Ana J. .
HEPATOLOGY, 2008, 47 (01) :186-198
[7]   Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion [J].
Hua, Fang ;
Ma, Jing ;
Ha, Tuanzhu ;
Xia, Yeling ;
Kelley, Jim ;
Williams, David L. ;
Kao, Race L. ;
Browder, I. William ;
Schweitzer, John B. ;
Kalbfleisch, John H. ;
Li, Chuanfu .
JOURNAL OF NEUROIMMUNOLOGY, 2007, 190 (1-2) :101-111
[8]   Matrix Metalloproteinase-2 (MMP-2) Gene Deletion Enhances MMP-9 Activity, Impairs PARP-1 Degradation, and Exacerbates Hepatic Ischemia and Reperfusion Injury in Mice [J].
Kato, Hiroyuki ;
Duarte, Sergio ;
Liu, Daniel ;
Busuttil, Ronald W. ;
Coito, Ana J. .
PLOS ONE, 2015, 10 (09)
[9]   Formononetin mediates neuroprotection against cerebral ischemia/reperfusion in rats via downregulation of the Bax/Bcl-2 ratio and upregulation PI3K/Akt signaling pathway [J].
Liang, Kun ;
Ye, Yu ;
Wang, Yong ;
Zhang, Jianfeng ;
Li, Chaoqian .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2014, 344 (1-2) :100-104
[10]   MMP-2 siRNA PROTECTS AGAINST CONTRACTILE DYSFUNCTION IN CARDIOMYOCYTES SUBJECTED TO ISCHEMIA/REPERFUSION [J].
Lin, H. ;
Sra, B. ;
Cadete, V. J. ;
Sawicka, J. ;
Cayabyab, F. S. ;
Sawicki, G. .
CANADIAN JOURNAL OF CARDIOLOGY, 2012, 28 (05) :S396-S397