GSK-3β抑制剂对大鼠脊髓损伤后细胞凋亡的影响

Effect of glycogen synthase kinase-3β inhibitor on cell apoptosis after spinal cord injury in rats

目的:观察GSK-3β抑制剂对大鼠脊髓损伤后细胞凋亡的影响。方法:健康雌性SD成年大鼠45只,采用WD法制作成T10平面完全性截瘫的脊髓损伤动物模型,并在L4平面蛛网膜下腔植入注药导管后随机分为3组,每组15只。A组为TDZD-8治疗组;B组:PBS治疗组;C组:手术瘫痪对照组。所用试剂均在手术后1 h内经导管内注射,TDZD-8(1 mg/kgd)和PBS(60μL/d),连续注射3周。各组在损伤后2 h、4 h、8 h、24 h、7 d(每个时相点3只大鼠)用TUNEL法检测细胞凋亡情况。结果:脊髓损伤后2 h开始出现凋亡细胞,此后,凋亡细胞逐渐增加,损伤后8 h阳性细胞达到高峰,50.3±4.3、58.7±2.2、58.9±2.8,损伤后24 h、7 d凋亡细胞数逐渐减少。不同的时间点TDZD-8治疗组阳性细胞数量均明显低于PBS治疗组和手术瘫痪对照组(P<0.05)。结论:TDZD-8能够抑制脊髓损伤后神经细胞凋亡,减少继发性脊髓损伤。

Objective： To investigate the effect of glycogen synthase kinase-3β（GSK-3β） inhibitor on cell apoptosis after spinal cord injury （SCI） in rats. Methods： A total of 45 healthy adult female Sprague-Dawley rats were selected, and the WD method was used to establish a rat model of SCI caused by complete paraplegia at the T10 level. A catheter was inserted into the subarachnoid space at the IA level and then the rats were randomly divided into three groups, with 15 rats in each group. The rats in group A were treated with TDZD-8 and those in group B were treated with PBS. Group C was control group. The rats in groups A and B were given TDZD-8 （1 mg/kg/d） or PBS （60 μL/d） via the catheter for 3 consecutive weeks. TUNEL method was used to measure cell apoptosis at 2, 4, 8, and 24 hours and 7 days after injury （three rats for each time point）. Results： Apoptotic cells started to occur at 2 hours after SCI （50.3 ± 4.3）, gradually increased at 4 hours after SCI （58.7 ±- 2.2）, and reached a peak at 8 hours after SCI （58.9 ± 2.8）. The number of apoptotic cells gradually decreased at 24 hours and 7 days after SCI. Compared with groups B and C, group A had a significantly lower number of positive cells at all time points （P 〈 0.05）. Conclusions： TDZD-8 can inhibit neuronal apoptosis after SCI and reduce secondary SCI.