大剂量甲基强的松龙对脊髓空洞前状态AQP4表达的影响

Effect of high-dose methylprednisolone on AQP4 expression during development of experimental presyrinx state in rabbits

目的探讨大剂量甲基强的松龙(MP)对AQP4表达的影响及其对实验性脊髓空洞前状态脊髓水肿的保护机制。方法选用新西兰白兔,制作动物模型并应用大剂量MP干预,采用干湿重法测定脊髓含水量,用免疫组化、Western blot和RT-PCR技术检测脊髓空洞前状态AQP4及其mRNA表达变化。结果Kaolin组动物于术后第1天脊髓含水量即有明显增加,第7天达到高峰, 21d时稍有缓解;AQP4于术后第1天开始减弱,第7-14天达到最低水平,到21d时回升;而AQP4 mRNA表达变化趋势与其蛋白含量变化相一致。MP组动物脊髓水肿时间延迟,程度显著减轻,上颈髓AQP4及其mRNA明显增高,以7d、14d最为显著。结论MP能够在基因和蛋白水平增加AQP4表达,促进水分子向血管腔和蛛网膜下腔转运,发挥抑制脊髓水肿作用。

Objective To investigate the effect of high-dose methylprednisolone on AQP4 expression and its neuroprotective mechanism of spinal edema during development of presyrinx state in rabbits. Methods The experimental syringomyelia models of rabbits were established by intra-cisternal injection of Kaolin. High-dose methylprednisolone was administered in animals of MP groups. The expression of AQP4,AQP4 mRNA and the water content of upper cervical spinal cord were measured with immunohistochemistry,Western blot, RT-PCR and dry-wet measure in 1,3,7, 14, 21d after operation respectively. Results The water content of upper cervical cord in Kaolin group animals increased from 1 st day, reached its peak at 7th day, lasted to 14th day, and then began to drop. AQP4 expression decreased in 3rd day after operation, reached its minimum at 7th day, lasted to 14th day, and recovered partially at 21 st day approximately. RT-PCR found the decreasing of AQP4 mRNA coincided well with that of AQP4 immunoreactive expression in presyrinx. Upper cervical cord edema in MP group showed to be delayed and obviously lessened, the AQP4 and its mRNA was significantly upregulated at each time point, especially in 7d and 14d after operation. Conclusion MP could obviously upregulated AQP4 and its mRNA expression in presyrinx state of experimental syringomyelia, the later helps to transport water to vessels and subarachnoid spaces to suppress edema formation of spinal cord.