RESUMO
Objective To investigate the therapeutic effects of intravenous monosialo ganglio-sides(GM-1)on neurotoxicity of intrathecally administered bupivacaine in rats and its possible mecha-nism.Methods One hundred and eight adult male Sprague-Dawley rats,weighing 280-300 g,were randomly divided into 3 groups (n=36 each):sham operation group (group sham),group saline and group GM-1.Neurotoxicity model was performed by injecting 0.12μl/g body weight of bupivacaine at concentrations of 5% via an implanted intrathecal catheter at 90-minute intervals for 4.5 h in groups saline and GM-1.After observing 24 h,group GM-1 was administered GM-1 30 mg/kg by intrave-nous injection for 7 days,once a day;while groups saline and sham received equal volume of normal saline.The recovery of the locomotor function was evaluated with Basso,Beattie and Bresnahan (BBB)and tail-flick latency(TFL)before injection bupivacaine and days 1,3,5,7,14,28 after in-jection,TFL was converted to the percent maximum possible effect (%MPE).Six rats were sacri-ficed in each group at each time point,and spinal cord was taken to examine histological injury scores by light and electron microscopy at the L3 level,and neuron caspase-3 expression was evluated using immunohistochemistry and RT-PCR.Results Compared with group saline,%MPE,histological inju-ry score and caspase-3 mRNA expression were decreased on days 7,14 and 28;Caspase-3 protein ex-pression was decreased on days 5,7,14 and 28;while BBB score was higher on days 14 and 28 in group GM-1 (P < 0.05 ).Compared with group sham,% MPE,histological injury score,caspase-3 mRNA and protein expression in groups GM-1 and saline were significantly higher,while BBB score was lower on 1,3,5,7,14 and 28 d after injection (P <0.05).Conclusion GM-1 can promote neuro-functional recovery after bupivacaine neurotoxicity in rats through the possible mechanism of down-regulating neuron caspase-3 expression.
RESUMO
Objective To evaluate the efficacy of intrathecally administered monosialoganglioside (GM-1)for treatment of bupivacaine spinal anesthesia-induced neurotoxicity to rat spinal cord.Methods Adult male Sprague-Dawley rats,weighing 280-300 g,in which the intrathecal catheter was successfully inserted into the L3,4 intervertebral space and advanced toward the tail,were randomly divided into 4 groups (n =36 each):sham operation group (group S),GM-1 group,bupivacaine group (group B) and bupivacaine + GM-1 group (group BG).In B and BG groups,the rats received 5％ bupivacaine 20 μl via the intrathecal catheter 3 times at 1.5-hour intervals.GM-1 20 μg was injected intrathecally 24 h later once a day for 7 days in BG and GM-1 groups.Before bupivacaine injection and on days 1,3,5,7,14 and 28 after bupivacaine injection (T0-T6),tail flick latency (TFL) was measured,MPE (percentage of maximal possible effect) was calculated,and the locomotor recovery was evaluated using the Basso,Beattie,Bresnahan (BBB) Locomotor Rating Scale.Then six rats were randomly chosen and sacrificed in each group.Spinal cord was removed for histopathologic examination (with light and electronic microscope) and for determination of caspase-3 protein and mRNA expression (by immuno-histochemistry and RTPCR).The pathological changes of the spinal cord were scored.Results Compared with S and GM-1 groups,MPE,pathological scores,and caspase-3 protein and mRNA expression were significantly increased and BBB score was decreased at T1-6 in group B (P ＜ 0.05),and MPE was increased at T1-5 (P ＜ 0.05) and returned to the baseline value at T6 (P ＞ 0.05) and pathological scores,and caspase-3 protein and mRNA expression were significantly increased and BBB score was decreased at T1-6 in group BG (P ＜ 0.05).There were no significant differences in each parameter at each time point between S and GM-1 groups (P ＞ 0.05).Compared with group B,MPE and caspase-3 protein and mRNA expression were significantly decreased at T2-6,pathological scores were decreased at T3-6,and BBB score was increased at T4-6 in group BG (P ＜ 0.05).The pathological changes of spinal cord tissues were obvious at T1-6 in group B and at T1-3 in group BG,but the changes gradually recovered at T4-6 in group BG.Conclusion Intrathecally administered GM-1 has therapeutic effect against bupivacaine spinal anesthesia-induced neurotoxicity to rat spinal cord,and inhibition of neuronal apoptosis in the spinal cord may be involved in the underlying mechanism.