盐酸利多卡因神经毒性损伤大鼠脊髓钙／钙调蛋白依赖性蛋白激酶Ⅱ的表达

Expression of calclum/calmodulin dependent protein kinase II in spinal cord of the rats followed iidocaine hydrochlorlde lntrathecal injection

目的观察大鼠鞘内注射盐酸利多卡因神经损伤后脊髓钙／钙调蛋白依赖性蛋白激酶Ⅱ（calcium／calmodulindependentproteinkinaseⅡ，CaMKⅡ）的表达变化。方法鞘内成功置管的雄性SD大鼠48只，体质量（230±20）g，用随机数字表法将大鼠分成4组（n=12，其中行为学检测大鼠8只，免疫印迹实验大鼠4只）：正常组（C组）、假手术组（S组）、溶媒组（D组）、10％利多卡因组（L组）。分别于给药前、给药后2h、4h、8h、12h、1d、2d、3d、4d、5d等时点检测大鼠机械缩腿阈值（Mechanicalwithdrawalthreshold，MWT）和热缩腿潜伏期（thermalwithdrawallatency，TWL）。并于给药后12h取4只大鼠脊髓腰膨大，免疫印迹检测大鼠脊髓腰膨大CaMKⅡ的表达。结果C组、S组和D组大鼠MWT的基础值分别为（11．2±3．1）g、（11．8±2．2）g和（11．4±2．4）g，其余各时间点与基础值比较差异无统计学意义（n=8，P〉0．05）；L组大鼠MWT在给药后2h、4h、8h、12h、1d、2d、3d、4d时点显著增加（n=8，P〈0．01），分别为（22．0±6．6）g、（22．2±5．3）g、（20．5±5．8）g、（18．5±4．3）g、（16．7±3．2）g、（15．2±3．1）g、（15．5±3．5）g、（13．7±2．4）g。与MWT结果相似，C组、S组和D组大鼠TWL的各时间点比较差异无统计学意义（n=8，P〉0．05）；L组大鼠TWL在给药后2h、4h、8h、12h、1d、2d、3d时点显著增加（n=8，P〈0．01）。C组、S组、D组及L组大鼠脊髓CaMKⅡ表达分别为0．17±0．03、0．16±0．03、0．19±0．05、0．42±0．11，L组大鼠表达显著增加（n=4，P〈0．01）。结论鞘内注射盐酸利多卡因可致脊髓CaMKⅡ表达显著增加，提示CaMKⅡ可能与盐酸利多卡因所致的神经损伤有关。

Objective To observe the expression of calcium/calmodulin dependent protein kinase II （ CaMK II ） in the spinal cord of the rats followed lidocaine hydrochloride intrathecal injection. Methods 48 male SD rats weight （230v 20）g, after intrathecal indwelling catheter, were randomly divided into four groups （n = 12, 8 rats for behavioral detection and 4 rats for western blotting） ：normal group （C group）, sham group （S group）, DMSO group （ D group）, 10% lidocaine group （ L group）. Mechanical withdrawal threshold（MWT） and thermal withdrawal latency（TWL） were detected before and after 2 h, 4 h, 8 h, 12 h, 1 d, 2 d, 3 d , 4 d and 5 d with drug treatment. Intumescentia lumbalis of the spinal cord were collected to measure the expression of CaMK II with western blotting after drug treatment for 12 h. Results The based MWT of the rats in C, S and D group were （ 11.2 ± 3.1 ） g, （ 11.8 ± 2.2 ） g and （ 11.4±2.4） g respectively. There were no differences among the every time points （ n = 8, P〉 0.05）. The MWT of the rats in L group significantly increased at 2 h, 4 h, 8 h, 12 h, 1 d , 2 d,3 d and 4 d after treatment with lidocaine hydrochloride, and the data were （22.0 ± 6.6） g, （22.2 ± 5.3 ） g, （20.5 ±5.8）8, （18.5 ±4.3）g, （16.7±3.2）g, （15.2 ±3.1）g, （15.5±3.5）g, （13.7±2.4）g respectively （ n=8, P〈0.01）. TWL had no difference among the rats in C, S, and D group（ n=8, P〉0.05）. The TWL of the rats in L group significantly increased at 2 h, 4 h, 8 h, 12 h, 1 d,2 d and 3 d after treatment with lidocaine hydroehloride （ n = 8, P 〈 0.01 ）. The expression of CaMK II of the rats in C group, S group, D group and L group were 0.17± 0.03,0.16 ± 0.03,0.19 ±0.05,0.42± 0.11, and significantly upregulated in L goup （ n = 4, P 〈 0.01）. Concision Lidocaine hydrochloride intrathecal injection can increase the expression of the CaMK II in the spinal cord of the rats. Those indicate that CaMK II may be involved with the nerve damage induced by lidocaine hydroehloride.