小剂量格列本脲对大鼠急性脊髓损伤后继发性损害的影响

Effects of low dose Glibenclamide on secondary damage after acute spinal cord injury in rats

目的 探讨格列本脲对大鼠脊髓损伤后继发性损害的保护作用.方法 90只SD大鼠随机分为3组,每组30只,即单纯椎板切除组（对照组）、脊髓损伤组（损伤组）与脊髓损伤后格列本脲治疗组（治疗组）.HE染色及电镜观察脊髓损伤后病理变化;免疫组织化学法检测脊髓损伤后45min、6 h、24 h、3 d、7 d的磺脲类药物受体1（sulfonylurea receptor type 1,SUR1）表达变化,利用IPP 6.0软件对SUR1的表达进行定量分析.采用BBB评分评价大鼠后肢功能的恢复.并对大鼠血糖进行定量检测.结果 HE染色显示：脊髓损伤后脊髓出血和胶质细胞增生随时间延长而加重,治疗组的组织出血、小胶质细胞增生和中性粒细胞浸润均较损伤组轻.电镜观察：治疗组的炎症细胞浸润、髓鞘板层结构破坏及线粒体肿胀程度等均较损伤组明显减轻.免疫组织化学染色显示：除45 min时SUR1尚未表达外,其余各时间点治疗组的SUR1表达均较损伤组弱.术后24 h,损伤组SUR1表达达高峰,此后随时间逐渐下降.三组各时间点的SUR1平均光密度经单因素方差分析,差异有统计学意义.治疗组大鼠BBB评分明显高于损伤组大鼠,各组差异有统计学意义.治疗组大鼠的血糖稍下降,但三组差异并无统计学意义.结论 格列本脲治疗能显著减轻脊髓的继发性损伤,促进脊髓功能恢复.格列本脲通过抑制SUR1的表达而发挥脊髓保护作用.

Objective To investigate the effects of Glibenclamide on reduction of secondary damage after acute spinal cord injury in rats.Methods Ninety rats were randomly divided into control group （laminectomy alone）,spinal cord injury group（injury group）,and treatment group（treated with Glibenclamide after spinal cord injury）,with 30 rats in each group.The pathological morphology changes of injured spinal cord were observed by HE staining and electron microscope.The expressions of sulfonylurea receptor 1 （SUR1）were detected by immunohistochemical method at 45 min,6 h,24 h,3 d and 7 d after spinal cord injury,and IPP 6.0 software were used for quantitative analysis.The function recoveries of the hind limbs of rats were evaluated by BBB score.The blood sugar level was detected quantitatively.Results HE staining showed that tissue bleeding and microglia proliferation getting severe with time after spinal cord injury.Compared to the injury group,tissue bleeding,microglia proliferation and inflammatory cell invasion was less severe in treatment group.Showed by electron microscope,inflammatory cell invasion,myelin sheath layer structure damage and mitochondrial swelling were significantly reduced after Glibenclamide treatment.Detected by immunohistochemical staining,the expressions of SUR1 at all time points after injury,except for 45 min that there were no SUR1 expressions in all groups,were much weaker in the treatment group than in the injury group.The SUR1 expression reached the peak at 24 h after injury in injury group,and decreased gradually with time.Significant differences were found in the SUR1 expression among three groups by oneway ANOVE.The BBB scores of treatment group were significant higher than that of injury group.The blood sugar slightly decreased in the treatment group,while no significant difference was found among three groups.Conclusion Glibenclamide can significant reduced the secondary damage after acute spinal cord injury.The protection of Glibenclamide after spinal cord injury may relate to its suppression of SUR1.