摘要
目的观察联合应用ROCKII和GSK-3β抑制剂对成体大鼠脊髓损伤后细胞凋亡的影响。方法①健康雌性SD成年大鼠80只,其中75只大鼠采用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5组,每组15只,A组为TDZD-8治疗组,B组为Y27632治疗组,C组为TDZD-8+Y27632联合治疗组,D组为PBS对照组,E组为手术对照组;F组5只正常大鼠作为空白对照组。所用试剂均在手术后1h内经导管鞘内注射。②脊髓损伤后各组在8、24h和1w三个时间点,采用TUNEL法检测脊髓细胞凋亡情况。结果在各观察时间点,A组至E组平均凋亡细胞数均高于F组,A组至C组在各观察时间点均低于D、E两组,C组在各观察时间点均低于A、B两组,差异均有统计学意义(P<0.05)。结论 Y27632和TDZD-8均可减少脊髓损伤后细胞凋亡,联合应用比单独应用的作用更明显。
Objective To explore the combined apoptosis inhibition effect of ROCKII and GSK-3β inhibitors on spi- nal cord injury in rats. Methods 75 adult female Sprague-Dawley (SD) rats were randomly allocated into 5 groups. The complete paraplegia at T10 level was made by the weight-drop impaction. A catheter was set into subarachnoid space at L4 level of the rats. Group A was treated with the GSK-3βinhibitor TDZD-8. Group B was treated with the ROCKII in- hibitor Y27632. Group C was treated with the combination of TDZD-8 and Y27632. Group D was treated with PBS. Group E was sham operation group. The other 5 rats (group F) were as normal control. All the reagents were injected respectively into subarachnoid space within 1 hour after operation. The number of apoptotic cells in the spinal cord lesion of every group was assessed by TUNEL assay at 8 hours, 24hours and 1 week respectively. Results Compared with group A to group E, the average apoptotie cell number in group F was significantly less at all three time points. The av- erage apoptotie cell number in group A to group C was significantly less than the number in group D and group E respec- tively, and the significantly lowest cell number was observed in group c. The differences between group A and group B, group D and group E were not significant. Conclusion Compared with the individual application of ROCKII and GSK-3β inhibitor, Y27632 and TDZD-8 respectively, the combination is more effective in reducing the apoptosis after spinal cord injury, and is likely beneficial for the prevention of secondary damage after initial trauma.
出处
《西部医学》
2012年第6期1059-1062,1066,共5页
Medical Journal of West China
基金
国家自然科学基金资助项目(30872602)