目的 探讨大剂量甲泼尼龙(methylprednisolone,MP)对急性脊髓损伤(acute spinal cord injury,ASCI)大鼠脊髓组织中内质网应激相关蛋白C/EBP家族的同源蛋白(C/EBP homology protein,CHOP)的影响.方法 48只SD大鼠采用Allen法制作ASCI模型,按随机数字表法分为MP治疗组(MP组,n=24)与生理盐水组(NS组,n=24),MP组在损伤后早期从尾静脉注射大剂量MP,对照组同样方法注射等量NS,分别于伤后3 h,1、3和7 d(3 h组、1 d组、3 d组和7 d组,每组6只)用改良Tarlov评分法评价其神经功能,再在各时间点处死动物,取受损节段脊髓HE染色及免疫组织化学观察其形态变化以及CHOP分布特点,同时用TUNEL方法检测细胞凋亡.其量的评定借助于IPP(Image-Pro Plus 6.0)软件,结果分别用累积光密度(integrated optical density,IOD)及平均光密度(mean density)表示.结果 MP组与NS组Tarlov评分分别为(3.583 3±0.583 6)分和(3.041 7±0.6903)分,MP组较NS组各个时间点后肢运动功能明显改善(P<0.01).CHOP在各组大鼠脊髓组织中均呈阳性表达,MP组CHOP表达明显低于NS组(P<0.05);MP组内,CHOP表达1d组和3 h组、3 d组的差异有统计学意义(P<0.05),且3 h组<1 d组>3 d组.MP组内各时间点的细胞凋亡差异有统计学意义(P<0.05),并且3h组<1 d组<3 d组>7 d组;NS组和MP组之间3 h、1 d、3 d之间的细胞凋亡差异有统计学意义(P<0.05).结论 大鼠ASCI后CHOP显著升高,早期应用大剂量MP对CHOP的表达具有明显的抑制作用.%Objective To investigate the effect of high-dose methylprednisolone (MP) on the expression of C/EBP homologous protein (CHOP) after acute spinal cord injury (ASCI) in rats. Methods A rat model of ASCI was established with the modified Allen's method. Forty-eighty ASCI rats were randomly assigned to receive tail vein injection of either high-dose MP(MP group, n = 24) or normal saline (NS group, n = 24). At 3 hours and 1,3 and 7 days after ASCI, nerve function was evaluated using modified Tarlov score and animals were sacrificed to collect the damaged segments of the spinal cord. Morphological changes were measured by HE staining. The expression of CHOP was detected hy immunohistochemistry. Cell apoptosis was examined hyrnTUNEL assay. Quantitative assessment was performed using IPP (Image-Pro Plus 6. 0) and resulted were presented as integrated optical density (IOD)and average optical density. Results The Tarlov scores were 3. 583 3 ± 0. 583 6 and 3. 041 7 ± 0. 690 3 in MP group and NS group,respectively. Compared with NS group,high-dose MP significantly improved hind limb motor func-tion(P<0. 01). Positive expression of CHOP was found in spinal cord tissue in both group. Compared with NS group,high-dose MP obviously decreased the expression of CHOP (P<0. 05). In MP group,CHOP expression at 1 day was higher than that at 3 hours and 3 days(P<0. 05). Furthermore, there were significant differences in cell apoptosis among different time points (3 h< 1 d<3 d>7 d)(P<0. 05). Moreover,differences in cell apoptosis were obvious at 3 hours and 1 and 3 days between NS group and MP group. Conclusion The expression of CHOP increases in rats after ASCI and early administration of high-dose MP can inhibit the expression of CHOP.
展开▼
