鞘内注射吗啡混合芬太尼对切口痛大鼠海马及血浆IFN-γ水平的影响

Effects of intrathecal morphine and fentanyl on IFN-γ levels in hippocampus and plasma of rats with incisional pain

目的:评价鞘内注射吗啡混合芬太尼对切口痛大鼠海马及血浆干扰素-γ(IFN-γ)水平的影响。方法:取鞘内置管术成功的健康雄性SD大鼠96只,体重180~220 g,6~8周龄,采用随机数字表法分为4组(n=24):生理盐水组(NS组)、切口痛组(P组)、吗啡混合芬太尼组(MF组)和吗啡混合芬太尼+切口痛组(MFP组)。P组和MFP组制备切口痛模型。造模前20 min时,MF组和MFP组鞘内注射吗啡5μg/kg和芬太尼0.25μg/kg的混合液50μl,NS组和P组鞘内注射生理盐水50μl。于造模前24 h(T_(0))、造模后1、6、24、48和72 h(T_(1~5))时,每组随机取6只大鼠,测定机械缩足反应阈(MWT)与热缩足潜伏期(TWL);于T_(0),T_(2),T_(3)和T_(5)时分别处死6只大鼠,取海马组织和下腔静脉血标本,采用ELISA法检测海马组织和血浆IFN-γ水平。结果:与NS组比较,P组T_(1~5)时MWT降低、TWL缩短,T_(2,3)和T_(5)时血浆IFN-γ浓度降低,MF组T_(1~3)时MWT升高、TWL延长,MFP组T_(1~4)时MWT降低、TWL缩短,MF组和MFP组T_(2)时血浆IFN-γ浓度降低(P<0.05);与P组比较,MF组和MFP组T_(1~5)时MWT升高、TWL延长,T_(2,3)和T_(5)时血浆IFN-γ浓度升高(P<0.05);与MF组比较,MFP组T_(1~4)时MWT降低、TWL缩短,T_(2,3)时血浆IFN-γ浓度升高(P<0.05)。4组各时点海马IFN-γ含量比较差异无统计学意义(P>0.05)。结论:鞘内注射吗啡混合芬太尼可提高切口痛大鼠血浆IFN-γ浓度,改善外周免疫抑制。

Objective To evaluate the effects of intrathecal morphine and fentanyl on interferon(IFN)-γlevels in hippocampus and plasma of rats with incisional pain.Methods Ninety-six healthy male Sprague-Dawley rats in which intrathecal catheters were successfully inserted,weighing 180-220 g,aged 6-8 weeks,were divided into 4 groups(n=24 each)using a random number table method:normal saline group(group NS),incisional pain group(group P),morphine and fentanyl group(group MF)and morphine and fentanyl with incisional pain group(group MFP).Incisional pain model was established in group P and group MFP.At 20 min before the model was established,a 50μl mixture of morphine 5μg/kg and fentanyl 0.25μg/kg was intrathecally injected in group MF and group MFP,while normal saline 50μl was injected intrathecally in group NS and group P.At 24 h before establishment of the model(T_(0))and at 1,6,24,48 and 72 h after establishment of the model(T_(1~5)),6 mice were randomly selected from each group for determination of the mechanical paw withdrawal threshold(MWT)and thermal paw withdrawal latency(TWL).The animals were sacrificed and hippocampal tissues and blood samples from the inferior vena cava were collected for determination of IFN-γlevels in hippocampal tissues and plasma(by enzyme-linked immunosorbent assay).Results Compared with group NS,MWT was significantly decreased and TWL was shortened at T_(1~5),and IFN-γconcentration in plasma was decreased at T_(2,3) and T_(5) in group P,MWT was increased and TWL was prolonged at T_(1~3) in group MF,MWT was decreased and TWL was shortened at T_(1~3) in group MFP,and IFN-γconcentration in plasma was decreased at T_(2) in MF and MFP groups(P<0.05).Compared with group P,MWT was increased,TWL was prolonged at T_(1~5),and IFN-γconcentration in plasma was increased at T_(2,3) and T_(5) in MF and MFP groups(P<0.05).Compared with group MF,MWT was decreased and TWL was shortened at T_(1~4),and IFN-γconcentration in plasma was increased at T_(2) and T_(3) in MFP(P<0.05).There was no significant difference in IFN-γconcentration at each time point among the 4 groups(P>0.05).Conclusion Intrathecal morphine and fentanyl can increase plasma IFN-γconcentration,and improve peripheral immunosuppression.