鞘内注射外源性神经生长因子对利多卡因致大鼠脊髓损伤的保护作用

The protective effect of exogenic nerve growth factor by intrathecal injection on lidocaine-induced neurotoxicity in rats

目的 探讨鞘内注射外源性神经生长因子（nerve growth factor,NGF）对利多卡因致脊髓神经毒性损伤的保护作用.方法 选择鞘内置管成功的大鼠60只,按随机数字表法分为生理盐水对照组（S组）和NGF治疗组（N组）两个大组,每大组分为P0、P1、P8三个不同时点的亚组,每组10只.S组P0亚组：仅行假手术,S组P1亚组,鞘内注射20％盐酸利多卡因20 μl;S组P8亚组,鞘内注射20％盐酸利多卡因20μl,连续7d鞘内注射NS,每次注射0.9％NS 20 μl;N组P0亚组：仅行假手术;N组P1亚组：鞘内注射20％盐酸利多卡因20 μl;N组P8亚组：鞘内注射20％盐酸利多卡因20μl,连续7d鞘内注射NGF,每次注射NGF 10 μg/20μl..连续评测两组中P8亚组大鼠的热痛阈值（tail-flick latency,TFL）及运动功能评分（motor function,Mr）,观察比较两组大鼠各亚组光镜及透射电镜下脊髓的病理改变.结果 与S组P8亚组比较,在5d～8d4个时点N组P8亚组的TFL最大镇痛效应百分率（percent of maximal possible potential effect,％MPE）（％MPETFL）显著降低[（62.5±20.3）％vs（32.6±23.5）％,（51.9±23.7）％vs（25.8±26.3）％,（43.8±22.5）％vs（20.5±24.3）％,（38.4±25.7）％vs（18.5±23.7）％]（P＜0.05）;且MF评分显著降低[3vs0,3vs0,3 vs0,3vs0]（P＜0.05）.光镜病理改变：S组P8亚组脊髓后角白质广泛水肿、脊膜细胞大量增生、广泛空泡变性;N组P8亚组见后角白质神经纤维水肿,脊膜细胞少量增生,空泡变性不明显.透射电镜病理改变：S组P8亚组见有髓神经纤维的髓鞘板层结构广泛肿胀疏松,无髓神经纤维模糊不清;N组P8亚组见有髓神经纤维的髓鞘板层结构局部疏松,可见肿胀的无髓神经纤维.结论 鞘内注射NGF能够减轻利多卡因引起的脊髓毒性损伤,改善脊髓神经细胞的超微结构.

Objective To investigate the protective effect of exogenic nerve growth factor （NGF） on lidocaine-induced neurotoxicity in rats.Methods After successful intrathecal catherization and positive lidocaine test,60 rats were randomly allocated into NS group （S group） and NGF groups （N group） which included P0,P1 and P8 subgroups with 10 in each subgroups.Two P0 subgroups：sham operation; Two P1 subgroups：20% lidocaine 20 μl intrathecal injection.Two P8 subgroups：20% lidocaine 20 μl intrathecal injection and NS/NGF 20 μl intrathecal injection on consecutive 7 d.TFL and MF on consecutive 7 din two P8 subgroups and the pathologic changes in the spinal cord by method of microscopy and electron scope were observed by a blind investigator in each subgroups.Results Compared with S group P8 subgroup,maximal effect proportion （MEP） of TFL [（62.5± 20.3）% vs （32.6±23.5）%,（51.9±23.7） % vs （25.8±26.3）%,（43.8±22.5）% vs （20.5±24.3）%,（38.4±25.7）% vs （18.5±23.7）%] （P〈0.05） and MF 3 vs 0,3 vs 0,3 vs 0,3 vs 0 （P〈0.05） were significantly decreased at the timing of 5 d-7 d.Edema vacuolar degeneration and interstitial edema in white matter of posterior horn of spinal cord were found in P8 subgroup of group S.On transmission electroscope,typical changes included interstitial edema,loosening of the laminae of myelinated fibers,axon swelling and local degeneration with most serious injury in P8 subgroup of group S,however,the above is improved in P8 subgroup of group S.Conclusions Exogenic NGF may repair the cells undergoing apoptosis therefore decrease the injury probably.