層粘連蛋白及基質金屬蛋白酶-9在大鼠局灶性腦缺血梗死區周圍的表達及意義_《華西醫學》

作者：

1 成都醫學院基礎醫學實驗教學中心（成都，610500）;2 四川大學華西醫院神經內科;3 成都醫學院附屬醫院普外科;

關鍵詞：

層粘連蛋白基質金屬蛋白酶-9 腦缺血大鼠

DOI：

10.7507/1002-0179.20130207

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目的　觀察局灶性腦缺血梗死區周圍層粘連蛋白（Laminin）及基質金屬蛋白酶（MMP）-9表達，探討其在腦缺血再灌注損傷發病機制中的作用。方法　將45只體重250～300 g、4個月齡的Sprague Dawley（SD）雄性大鼠隨機分為假手術（Sham）組與局灶性缺血再灌注（MCAO）組。MCAO組又分6、24、72 h及7 d組，每組各9只。光學顯微鏡下觀察腦組織病理改變，免疫組織化學染色檢測各組Laminin及MMP-9的表達情況。結果　再灌注后6 h，即有MMP-9表達明顯增高，表達高峰出現在再灌注后24 h，3 d時有所下降，至7 d時仍明顯高于基礎水平
（P＜0.01）。Laminin的表達于再灌注6 h開始降低，24 h降至最低，3 d后開始緩慢回升。結論　腦缺血再灌注后，病變區MMP-9與Laminin表達變化可反映腦血管壁受損狀況，并與腦缺血損傷及修復過程有關。

引用本文： 胡曉松,周東,唐瑜,劉靜,李娟. 層粘連蛋白及基質金屬蛋白酶-9在大鼠局灶性腦缺血梗死區周圍的表達及意義. 華西醫學, 2013, 28(5): 651-654. doi: 10.7507/1002-0179.20130207 復制

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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.	王嶸, 胡曉松, 龍啟福, 等. 局灶性腦缺血預處理對大鼠梗死區周圍巢蛋白表達的影響[J]. 基礎醫學與臨床, 2011, 31(12): 1341-1345.

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. 　陳紅兵, 郭云良, 孫圣剛, 等. 大鼠腦缺血再灌流后基質金屬蛋白酶2和9的表達[J].解剖學雜志, 2005, 28(3): 304-307.
9. 　張微微, 魏亞洲, 周小英. 大鼠腦缺血/再灌注層粘連蛋白表達的實驗研究[J]. 北京醫學, 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. 　王嶸, 胡曉松, 龍啟福, 等. 局灶性腦缺血預處理對大鼠梗死區周圍巢蛋白表達的影響[J]. 基礎醫學與臨床, 2011, 31(12): 1341-1345.

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層粘連蛋白及基質金屬蛋白酶-9在大鼠局灶性腦缺血梗死區周圍的表達及意義

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