Expression of Laminin and Matrix Metalloproteinase-9 around the Infarct Area Following Focal Ischemia in Rat Brains and Its Significance_West China Medical Journal

Authors：

1. Basic Medical Experimental Teaching Centre, Chengdu Medical College, Chengdu, Sichuan 610500, P. R. China; 2. Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China; 3. Department of General Surgery, Chengdu Medical College Hosipital, Chengdu, Sichuan 610513, P. R. China;

Corresponding author：

Keywords：

层粘连蛋白; 基质金属蛋白酶-9; 脑缺血; 大鼠

DOI：

10.7507/1002-0179.20130207

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目的　观察局灶性脑缺血梗死区周围层粘连蛋白（Laminin）及基质金属蛋白酶（MMP）-9表达，探讨其在脑缺血再灌注损伤发病机制中的作用。方法　将45只体重250～300 g、4个月龄的Sprague Dawley（SD）雄性大鼠随机分为假手术（Sham）组与局灶性缺血再灌注（MCAO）组。MCAO组又分6、24、72 h及7 d组，每组各9只。光学显微镜下观察脑组织病理改变，免疫组织化学染色检测各组Laminin及MMP-9的表达情况。结果　再灌注后6 h，即有MMP-9表达明显增高，表达高峰出现在再灌注后24 h，3 d时有所下降，至7 d时仍明显高于基础水平
（P＜0.01）。Laminin的表达于再灌注6 h开始降低，24 h降至最低，3 d后开始缓慢回升。结论　脑缺血再灌注后，病变区MMP-9与Laminin表达变化可反映脑血管壁受损状况，并与脑缺血损伤及修复过程有关。

Citation： HU Xiaosong,ZHOU Dong,TANG Yu,LIU Jing,LI Juan.. Expression of Laminin and Matrix Metalloproteinase-9 around the Infarct Area Following Focal Ischemia in Rat Brains and Its Significance. West China Medical Journal, 2013, 28(5): 651-654. doi: 10.7507/1002-0179.20130207 Copy

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1. 　Lo EH. A new penumbra: transitioning from injury into repair after stroke[J]. Nature Med, 2008, 14(5): 497-500.
2. 　Moskowitz MA, Lo EH, Iadecola C. The Science of stroke: mechanisms in search of treatments[J]. Neuron , 2010, 67(2): 181-198.
3. 　Longa EZ, Weinstein PR, Calson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1): 84-86.
4. 　Rosenberg GA. Matrix metalloproteinases and their multiple roles in neurodegenerative diseases[J]. Lancet Neurol, 2009, 8 (2): 205-216.
5. 　Zhang H, Trivedi A, Lee J-U, et al. Matrix metalloproteinase-9 and stromal cell-derived factor-1 act synergistically to support migration of blood-borne monocytes into the injured spinal cord[J]. J Neurosci 2011, 31(44): 15894-15903.
6. 　Gu Z, Cu i J, Brown, et al. A highly specific inhibitor of matrix metalloproteinase-9 rescues laminin from proteolysis and neurons from apoptosis in transient focal cerebral ischemia[J]. J Neurosci, 2005, 25(27) : 6401-6408.
7. 　Lee H, Park JW, Kim SP, et al. Doxycycline inhibits matrix metalloproteinase-9 and laminin degradation after transient global cerebral ischemia[J]. Neurobiol Dis, 2009, 34(1): 189-198.
8. 　陈红兵, 郭云良, 孙圣刚, 等. 大鼠脑缺血再灌流后基质金属蛋白酶2和9的表达[J].解剖学杂志, 2005, 28(3): 304-307.
9. 　张微微, 魏亚洲, 周小英. 大鼠脑缺血/再灌注层粘连蛋白表达的实验研究[J]. 北京医学, 2005, 27(7): 408-410.
10. 　Jia F, PanYH, M ao Q, et al. Matrix metalloproteinase-9 expression and protein levels after fluid percussion injury in rats: the effect of injury severity and brain temperature[J]. J Neurotrauma, 2010, 27(6): 1059-1068.
11. 　Tong L, Smyth D, Kerr C, et al. Mitogen-activated protein kinases Erk1/2 and p38 are required for maximal regulation of TIMP-1 by oncostatin M in murine fibroblasts[J]. Cell Signal, 2004, 16(10): 1123-1132.
12. 　Asahi M, Wang X, Mori T, et al. Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia[J]. J Neurosci, 2001, 21(19): 7724-7732.
13. 　Higashida T, K reipke CW, Rafols JA, et al. The role of hypoxia inducible factor-1 alpha, aquaporin-4, and matrix metallo roteinase-9 in blood-brain barrier disruption and brain edema after traumatic brain injury[ J] . J Neuro surg, 2010, 6(10) : 1162-1168.
14. 　Esposito E, Iacono A, Muia´ C, et al. Signal transduction pathways involved in protective effects of melatonin in C6 glioma cells[J]. J Pineal Res, 2008, 44(1):78-87.
15. 　Nelson KK, Subbaram S, Connor KM, et al. Redoxdependent matrix metalloproteinase-1 expression is regulated by JNK through Ets and AP-1 promoter motifs[J]. J Biol Chem, 2006, 281(15): 14100-14110.
16. 　English JL, Kassiri Z, Koskivirta I, et al. Individual TIMP deficiencies differentially impact pro-MMP-2 activation[J]. J Biol Chem 2006, 281(15): 10337-10346.
17. 　Van den Steen PE, Dubois B, Nelissen I, et al. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9) [J]. Crit Rev Biochem Mol Biol, 2002, 37(6): 375-536.
18. 　王嵘, 胡晓松, 龙启福, 等. 局灶性脑缺血预处理对大鼠梗死区周围巢蛋白表达的影响[J]. 基础医学与临床, 2011, 31(12): 1341-1345.

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Expression of Laminin and Matrix Metalloproteinase-9 around the Infarct Area Following Focal Ischemia in Rat Brains and Its Significance

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