右美托咪定对利多卡因致大鼠脊髓神经损伤的影响

摘要

目的 评价右美托咪定对利多卡因致大鼠脊髓神经损伤的影响.方法 雄性SD大鼠24只,体重250～280 g,采用随机数字表法分为三组(n=8):对照组(C组)、利多卡因组(L组)、右美托咪定+利多卡因组(DL组).C组仅行鞘内置管术,L组和DL组在鞘内置管后鞘内注射10％盐酸利多卡因20 μL,其中DL组在鞘内注射利多卡因前1h,腹腔注射右美托咪定15μg/kg.分别于术前1d(基础值)及术后1、2、3d时测定热缩足潜伏期(TWL).于术后3d行为学测定结束后处死大鼠,取脊髓组织,采用TUNEL染色测定大鼠脊髓神经元细胞凋亡率,Westernbolt测定脊髓肿瘤坏死因子-o (TNF-α)和白细胞介素-8(IL-8)表达水平.结果 三组大鼠TWL基础值比较,差异无统计学意义(P＞0.05);C组大鼠各时点TWL比较,差异无统计学意义(P＞0.05);与C组比较,L组大鼠术后1、2、3d时TWL均延长(P＜ 0.05);与L组比较,DL组大鼠术后2、3d时TWL均缩短(P＜0.05).与C组比较,L组大鼠脊髓神经元细胞凋亡率升高(P＜0.05);与L组比较,DL组大鼠脊髓神经元细胞凋亡率降低(P＜0.05).与C组比较,L组大鼠脊髓内TNF-α和IL-8的表达增强(P＜0.05);与L组比较,DL组大鼠脊髓内TNF-α和IL-8的表达减弱(P＜0.05).结论 右美托咪定通过抗神经元细胞凋亡减轻利多卡因所致的大鼠脊髓神经损伤,其机制与抑制炎性反应的发生有关.%Objective To evaluate the influence of Dexmedetomidine on Lidocaine-induced spinal cord never injury in rats.Methods 24 male SD rats weighting from 250 to 280 g were divided into three groups (n=8) by random number table:control group (Group C),Lidocaine group (Group L) and Dexmedetomidine+Lidocaine group (Group DL).Group C was only given intrathecal cathetering,while group L and group DL were given 20 μL of 10％ Lidocaine hydrochloride via intrathecal injection after intrathecal cathetering,where group DL was given 15 μg/kg of Dexmedetomidine via abdominal injection 1 h before intrathecal injection of Lidocaine.Thermal withdrawal latency (TWL) was determined on 1 d before operation (baseline) and postoperative 1,2 and 3 d.The rats were sacrificed at the end of behavior determination at postoperative 3 d,and the spinal cord tissues were taken.TUNEL staining was used to determine the apoptosis of rat spinal neurons,and Western blot was used to determine the expressions of TNF-o and IL-8.Results There were no statistical differences among each group of rats in baseline TWL (P ＞ 0.05),and there were no statistical differences in baseline rat TWL in group C among different time points (P ＞ 0.05).Compared with group C,rat TWL of group L were all prolonger at postoperative 1,2 and 3 d (P ＜ 0.05).Compared with group L.rat TWLs of group DL were all shorter at postoperative 2 and 3 d (P ＜ 0.05).Compared with group C,cell apoptosis rate of spinal neuron was increased and the expressions of TNF-α and IL-8 were increased in group L (P ＜ 0.05).Compared with group L,cell apoptosis rate of spinal neuron was decreased and the expressions of TNF-α and IL-8 were decreased in group DL (P ＜ 0.05).Conclusion Dexmedetomidine can reduce the Lidocaine-induced spinal cord never injury in rats by anti-apoptosis of neurons,and the mechanism is related to inhibition on inflammation.