Objective  To observe the activity alteration of MMP-9

and investigate the protective effect of doxycycline on brain tissue after cerebral ischemia-reperfusion injury in rats.   Methods  Cerebral ischemia-reperfusion model was induced by middle cerebral artery occlusion (MCAO). SD rats were divided into sham-operated group

saline group and doxycycline group

18 rats in each group. The laser-doppler probe was fixed before and after operation (MCAO)

and at reperfusion 24 h

to measure local cerebral blood flow (CBF) in an area supplied by the middle cerebral artery. The infarct volume was defined by 2

3

5-triphenyltetrazolium chloride (TTC) staining at reperfusion 24 h. Gelatin zymography was used to determine the activity of MMP-9 in the cerebral ischemic tissue. Neuron ultrastructure was investigated by transmission electron microscopy (TEM) in the rat ischemic cerebral cortex.   Results  There was significant change between the cerebral blood flow (CBF) [(57.98±4.20)%

(59.23±3.30)% respectively of the base line] at reperfusion 24 h and MCAO [ (22.94±3.16 )%

( 21.63±3.46)% of the base line] (P0.01)

but no significant difference was seen between the saline and doxycycline groups at same time point (P0.05). The cerebral infarction volume in doxycycline group [(9.77±2.68)%] was significantly decreased than that in saline group [(33.44±4.50)%] (P0.01). The activity of MMP-9 in saline group (5.95±0.73) were significantly increased compared with the sham-operation group (1.21±0.15) at reperfusion 24 h (P0.01). Doxycycline (2.47±0.42) significantly inhibited the enhanced activity of MMP-9 at reperfusion 24 h (P0.01). Neuron ultrastructure was abnormal change in saline group

but there was obvious recovery for the abnormal neuron ultrastructure in doxycycline group.   Conclusion  Doxycycline exerts a protective effect on focal cerebral ischemia-reperfusion injury in rats by inhibiting MMP-9 activity.