RESUMO
Objective To investigate the protective effect of meglumine adenosine cyclosphosp (MAC) on the cerebral ischemia-reperfusion (I/R) injury in rabbits.Methods Twenty four healthy rabbits were randomly divided into control group (n =6),I/R group (n =6),MAC pretreated group (n =6),and MAC treated group (n =6).Cerebral ischemia-reperfusion injury model was made by separating and electrocoagulating vertebral arteries and clipping common carotid arteries in the latter 3 groups after anesthesia.The sham-operated group underwent vessel separation without clipping.L/R group was administered with nothing,while MAC pretreated group with MAC before ischemia,and MAC treated group with MAC just after ischemia.Blood was gathered from jugular vein before ischemia,and 30 min,1 h,and 2 h after reperfusion for testing IL-8,superoxide dismutase (SOD) and malondialdehyde (MDA).The brain tissue slice was observed by optical microscope.Results Compared to control group and before ischemia,the levels of IL-8 and SOD in serum were significantly increased and decreased,and the levels of MDA was significantly increased at 30 min after reperfusion in I/R group; the levels of IL-8 and MDA in serum were significantly increased,and the levels of SOD in serum was significantly decreased at 1 h and 2 h after reperfusion in I/R group.The levels of IL-8 in serum was less at 30 min and 1 h and 2 h after reperfusion in MAC pretreated group than in I/R group.At 1 h and 2 h after reperfusion,the levels of MDA in serum was less and the levels of SOD in serum was higher in MAC pretreated group than in I/R group.At 1 h and 2 h after reperfusion,the levels of IL-8 in serum were less and the levels of SOD in serum were higher in MAC treated group than in I/R group.The levels of MDA in serum were less at 2 h after reperfusion in MAC treated group than in I/R group.Compared to I/R group,pathological change was lighter in the MAC pretreated and MAC treated group.Conclusions MAC has a fine cerebral-protective effect and has no side effect.
RESUMO
Objective To investigate the analgesic effect of a specific p38MAPK inhibitor SB203580 in a rat model of chronic constriction injury (CCI) to sciatic nerve. Methods Male SD rats weighing 220-250 g were used in this study. The neuropathic pain model was established by CCI to sciatic nerve. The rats were anesthetized with intraperitoneal (i.p.) pentobarbital 40 mg?kg-1. Left sciatic nerve was exposed and 4 loose ligatures were placed on left sciatic nerve at 1 mm intervals with 4-0 silk suture. The animals were allowed 7 days to recover from surgery. Intrathecal (IT) SB203S80 was given through a needle inserted at L5,6 interspace. In experiment A, 40 rats wee randomly divided into 5 groups (n = 8 each): control group and 4 SBgroups (SB203580 0.1, 0.5, 2.5 and 5.0 ?g were given respectively) . Response of the hindpaw to mechanical stimulation with von Frey filament (MWT) was measured before (T0,baseline) and at 0.5, 3, 6, 12 and 24 h (T1-5) after IT SB203580 injection. In experiment B, 36 animals were randomly divided into 6 groups (n = 6 each): (1) sham operation group; (2) CCI group; (3) DMSO group; (4) SB 0.1 ?g group; (5) SB 0.5 ?g group and (6) SB 5.0 ?g group. The animals were lulled at 6h after IT SB203580 administration and L5,6 lumbar segment of the spinal cord was removed for determination of pCREB expression in the dorsal horn by immuno-cytochemistry. Results The rats developed hyperalgesia after CCI and IT SB203580 administration significantly increased MWT in a dose dependent manner. The number of pCREB positive neurons in the L4,5 spinal dorsal horn was significantly increased after CCI. Interthecal administration of SB203580 0.5 or 5.0 ?g significantly inhibited the CCI-induced increase in pCREB expression. Conclusion Intrathecal administration of SB203580 can attenuate the hyperalgesia induced by CCI and inhibition of CREB phosphorylation in the spinal dorsal horn is involved in the mechanism.