[目的]观察氯化锂对脊髓损伤后BDNF/TrkB信号表达的作用,探讨其对脊髓损伤大鼠肢体运动功能恢复的作用和机制。[方法]36只SD大鼠随机分为假手术组(12例)、对照组(12例)、氯化锂组(12例),假手术组仅行椎板切除术,对照组和氯化锂组采用NYU脊髓打击器建立脊髓损伤模型,术后第1、3、5 d和第7 d行BBB肢体运动功能评分。干预7 d后取材,采用尼氏染色光镜观察神经元形态,免疫荧光定位BDNF阳性细胞,并计数进行半定量分析,Western blot检测BDNF蛋白、TrkB蛋白和p-TrkB蛋白表达。[结果]在脊髓损伤后肢体运动功能方面,自干预后第3 d起,氯化锂组BBB评分高于对照组,差异具有统计学意义(P〈0.05),至术后第5 d,两组间BBB评分差异更加明显(P〈0.01)。尼氏染色提示氯化锂组脊髓损伤后神经元的形态优于对照组。氯化锂组脊髓损伤后脊髓前角运动神经元BDNF阳性细胞数高于对照组,差异具有统计学意义(P〈0.01);Western blot检测表明氯化锂组的BDNF蛋白和p-TrkB蛋白表达高于对照组,两组间差异有统计学意义(P〈0.05),但两组间TrkB蛋白表达差异无统计学意义(P〉0.05)。[结论]氯化锂能促进脊髓损伤对照大鼠肢体运动功能恢复,其机制可能与其促进脊髓损伤后脊髓前角运动神经元分泌BDNF,促进TrkB受体磷酸化,从而上调BDNF/TrkB信号表达,促进脊髓损伤后神经元存活、再生和轴突再生、再髓鞘化有关。
[Objective] To investigate the role of lithium chloride on the expression of BDNF/TrkB pathway in a spinalcord injury( SCI) rat model and analyze the mechanism of lithium chloride for recovery of motor function. [Method] Thirty-six SD rats were randomly divided into the sham operation group( n=12), control group( n=12) and lithium chloride group( n=12). Only laminectomy was conducted in the animals of the sham operation group, whereas the spinal cord injury model was es-tablished by NYU spinal cord impactor in the control group and lithium chloride group. After surgery, lithium chloride was intra-peritoneally given at 3mg/Kg once per day in the animals of the lithium chloride group, whereas the same dose of normal salinewere given for those in sham operation group and the control group. BBB score was used to evaluate the motor function at 1, 3, 5,7 days after administration, then tissues samples were harvested for Nissl's staining, transmission electron microscope observa-tion, immunofluorescence analysis and western blot test. [Results] In term of motor function, the lithium chloride group gotsignificantly higher BBB scores than those in the control group at 3 days after administration(P〈0.05), with further increaseddifferences between the two groups at 5 days( P〈0.01). Additionally, Nissl's staining revealed that much better structure andmorphology of neuron remained in the lithium chloride group compared to the control group. Furthermore, the number of BDNFpositive cells in the spinal cord anterior horn was significant-ly higher in the lithium chloride group than the controlgroup( P〈0.01). Moreover, Western blot test showed expres-sion of BDNF protein and phosphorylated TrkB protein inthe lithium chloride group were likewise significantly higherthan the control group( P〈0.05), however, no significantdifference in the expression of TrkB was detected betweenthe two groups. [Conclusions] Lithium chloride does im-prove the motor function recovery after spinal cord injury