T型钙通道在鞘内注射利多卡因致大鼠脊髓神经毒性中的作用

Role of T-type calcium channel in spinal neurotoxicity of intrathecal lidocaine in rats

目的评价T型钙通道在鞘内注射利多卡因致大鼠脊髓神经毒性中的作用。方法鞘内置管成功的成年雄性sD大鼠48只，体重230～270g，采用随机数字表法，将其随机分为4组（n=12）：二甲基亚砜组（D组）、10％利多卡因组（L组）、米贝地尔＋利多卡因组（M组）和生理盐水＋利多卡因组（N）组，另取12只大鼠作为正常对照组（C组）。D组和L组分别鞘内注射二甲基亚砜和10％利多卡因20μl，M组和N组分别鞘内注射米贝地尔200μl/10μl和生理盐水10μl后鞘内注射10％利多卡因20μl。于鞘内给药前、给药后2、4、8、12h、1、2、3、4和5d（T0-9）时测定大鼠后肢机械缩足反应阈值（MWT）和热缩足反射潜伏期（TWL）。于T6时每组随机取4只大鼠处死取脊髓腰膨大，光镜下观察病理学结果。结果与c组比较，D组各时点MWT和TWL差异无统计学意义（P〉0．05），L组和N组T1-8时MWT升高，T1～7时TWL延长，M组，T1-6时MWT升高，TWL延长（P〈0．05）；与L组和N组比较，M组T1～4时MWT降低，TWL缩短（P〈0．05）。M组较L组和N组脊髓病理学损伤减轻。结论T型钙通道参与了鞘内注射利多卡因致大鼠脊髓神经毒性的过程。

Objective To investigate the role of T-type calcium channel in the spinal neurotoxicity of intrathecal （IT） lidocaine in rats. Methods Forty-eight adult male SD rats in which IT catheter was successfully implanted, weighing 230-270 g, were randomly divided into 4 groups （n = 12 each）： dimethyl sulfoxide （DMSO） group （group D）, lidocaine group （group L）, mihefradil ＋ lidocaine group （group M）, normal saline ＋ lidocaine group （group N）. Another 12 rats served as control group （group C）. DMSO and 10% lidocaine 20μl were injected intrathecally in groups D and L respectively. After mibefradil 200 μg/10μl and normal saline 10μl were injected intrathecally in groups M and N respectively, 10% lidocaine 20 μl was injected intrathecally in the two groups. The mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） were measured be- fore IT injection and at 2, 4,8 and 12 h and 1, 2, 3, 4 and 5 d after IT injection （T0-9 ）. Four rats were sacrificed at T6 in each group and their lumbar enlargements were removed for microscopic examination. Results Compared with group C, no significant change in MWT and TWL was found at each time point in group D, MWT was signifi- cantly increased at Tl_s and TWL was significantly prolonged at T1-7 in groups L and N, and MWT was significantly increased at T1.6 and TWL was significantly prolonged at T1.6 in group M （ P 〈 0.05 ） . Compared with groups L and N, MWT was significantly decreased at T1.4 and TWL was significantly shortened at T1-4 in group M （ P 〈 0.05）. Pathological injury was significantly reduced in group M as compared with groups L and N. Conclusion T-type calcium channel is involved in the spinal neurotoxicity of IT lidocaine in rats.