Effect of encapsulation in liposomes on toxic effect of bupivacaine on spinal cord in rats / 中华麻醉学杂志

ABSTRACT

ObjectiveTo study the toxic effect of bupivacaine encapsulated in liposomes on spinal cord in rats.MethodsOne hundred and eight SD rats (200-225 g) in which intrathecal (IT) catheter was successfully implanted without complications were randomly divided into 6 groups ( n =18 each)control group (group C) ; liposome group (group L) ; 0.5％ and 1.0％ bupivacaine groups (groups B1 and B2 ) and 0.5％ and 1.0％ bupivacaine encapsulated in liposomes groups (groups LB1 and LB2 ).In groups L,B1,B2,LB1 and LB2,liposome,0.5 ％ bupivacaine,1.0 ％ bupivacaine,0.5 ％ liposomal bypivacaine and 1.0 ％ liposomal bupivacaine 20 μl were injected IT respectively once a day for 7 consecutive days,while in group C nothing was injected IT.Pain threshold was measured by mechanical stimulation of the plantar surface of hindpaw.Motor function of the hindlimbs was also assessed.The animals were sacrificed at 8 day after IT injection.The lumbar segment of the spinal cord was removed for microscopic examination,detection of neuronal apoptosis (by flow cytometry) and Fos protein expression (by immuno-histochemistry).Results1.0％ bupivacaine IT significantly increased the percentage of apoptotic neurons in group B2 as compared with control group.0.5％ and 1.0％ bupivacaine IT significantly increased the number Fos protein positive cells in group B1 and B2 as compared with group C.1.0％ bupivacaine IT induced severe histologic damage including shrinkage of nucleus and vacuole formation in mitochondria.Encapsulation of bupivacaine in liposomes significantly attenuated bupivacaine-induced increase in apoptosis and Fos protein expression and histologic damage in group LB2 as compared with group B2.ConclusionThe encapsulation in liposomes can decrease the neurotoxicity of 1.0 ％ bupivacaine administered IT in rats.