Minocycline inhibits 5-lipoxygenase activation and brain inflammation after focal cerebral ischemia in rats

被引:61
作者
Chu, Li-sheng
Fang, San-hua
Zhou, Yu
Yu, Guo-liang
Wang, Meng-ling
Zhang, Wei-ping
Wei, Er-qing [1 ]
机构
[1] Zhejiang Univ, Sch Med, Dept Pharmacol, Hangzhou 310058, Peoples R China
[2] Zhejiang Chinese Med Univ, Dept Physiol, Hangzhou 310053, Peoples R China
关键词
minocycline; 5-lipoxygenase; leukotriene; focal cerebral ischemia; inflammation;
D O I
10.1111/j.1745-7254.2007.00578.x
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Aim: To determine whether the anti-inflammatory effect of minocycline on postis-chemic brain injury is mediated by the inhibition of 5-lipoxygenase (5-LOX) expression and enzymatic activation in rats. Methods: Focal cerebral ischemia was induced for 30 min with middle cerebral artery occlusion, followed by reperfusion. The ischemic injuries, endogenous IgG exudation, the accumulation of neutrophils and macrophage/microglia, and 5-LOX mRNA expression were determined 72 h after reperfusion. 5-LOX metabolites (leukotriene B-4 and cysteinyl leukotrienes) were measured 3 h after reperfusion. Results: Minocycline (22.5 and 45 mg/kg, ip, for 3 d) attenuated ischemic injuries, IgG exudation, and the accumulation of neutrophils and macrophage/microglia 72 h after reperfusion. It also inhibited 5-LOX expression 72 h after reperfusion and the production of leukotrienes 3 h after reperfusion. Conclusion: Minocycline inhibited postischemic brain inflammation, which might be partly mediated by the inhibition of 5-LOX expression and enzymatic activation.
引用
收藏
页码:763 / 772
页数:10
相关论文
共 48 条
[1]   INTRACAROTID INFUSION OF LEUKOTRIENE-C4 SELECTIVELY INCREASES BLOOD-BRAIN-BARRIER PERMEABILITY AFTER FOCAL ISCHEMIA IN RATS [J].
BABA, T ;
BLACK, KL ;
IKEZAKI, K ;
CHEN, K ;
BECKER, DP .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1991, 11 (04) :638-643
[2]   P2Y1 and cysteinyl leukotriene receptors mediate purine and cysteinyl leukotriene co-release in primary cultures of rat microglia [J].
Ballerini, P ;
Di Iorio, P ;
Ciccarelli, R ;
Caciagli, F ;
Poli, A ;
Beraudi, A ;
Buccella, S ;
D'Alimonte, I ;
D'Auro, M ;
Nargi, E ;
Patricelli, P ;
Visini, D ;
Traversa, U .
INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 2005, 18 (02) :255-268
[3]   TIME-RELATED CHANGES IN MYELOPEROXIDASE ACTIVITY AND LEUKOTRIENE B-4 RECEPTOR-BINDING REFLECT LEUKOCYTE INFLUX IN CEREBRAL FOCAL STROKE [J].
BARONE, FC ;
HILLEGASS, LM ;
TZIMAS, MN ;
SCHMIDT, DB ;
FOLEY, JJ ;
WHITE, RF ;
PRICE, WJ ;
FEUERSTEIN, GZ ;
CLARK, RK ;
GRISWOLD, DE ;
SARAU, HM .
MOLECULAR AND CHEMICAL NEUROPATHOLOGY, 1995, 24 (01) :13-30
[4]   Inflammatory mediators and stroke: New opportunities for novel therapeutics [J].
Barone, FC ;
Feuerstein, GZ .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1999, 19 (08) :819-834
[5]   Protective effect of the 5-lipoxygenase inhibitor AA-861 on cerebral edema after transient ischemia [J].
Baskaya, MK ;
Hu, YG ;
Donaldson, D ;
Maley, M ;
Rao, AM ;
Prasad, MR ;
Dempsey, RJ .
JOURNAL OF NEUROSURGERY, 1996, 85 (01) :112-116
[6]   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
[7]   Rapid import of cytosolic 5-lipoxygenase into the nucleus of neutrophils after in vivo recruitment and in vitro adherence [J].
Brock, TG ;
McNish, RW ;
Bailie, MB ;
PetersGolden, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (13) :8276-8280
[8]   TRANSLOCATION AND LEUKOTRIENE SYNTHETIC CAPACITY OF NUCLEAR 5-LIPOXYGENASE IN RAT BASOPHILIC LEUKEMIA-CELLS AND ALVEOLAR MACROPHAGES [J].
BROCK, TG ;
MCNISH, RW ;
PETERSGOLDEN, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (37) :21652-21658
[9]   Production of leukotrienes in a model of focal cerebral ischaemia in the rat [J].
Ciceri, P ;
Rabuffetti, M ;
Monopoli, A ;
Nicosia, S .
BRITISH JOURNAL OF PHARMACOLOGY, 2001, 133 (08) :1323-1329
[10]   Inflammatory mechanisms after ischemia and stroke [J].
Danton, GH ;
Dietrich, WD .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2003, 62 (02) :127-136