甲泼尼龙对实验性变态反应性脑脊髓炎大鼠SRp30c的影响

Effects of methylprednisolone on expression of SRp30c in experimental allergic encephalomyelitis in rats

目的研究不同剂量甲泼尼龙(MP)作用于实验性变态反应性脑脊髓炎(EAE)大鼠模型后,剪接因子SRp30c的表达及其与疗效的关系,探讨MP治疗作用及发生激素抵抗的可能机制。方法构建Wistar大鼠EAE模型,将EAE大鼠分成大剂量组、小剂量组、模型对照组,分别通过尾静脉注射MP 100 mg/kg、25 mg/kg、等容量生理盐水;另取未造模大鼠作为正常对照组,予等容量生理盐水注射。给药5d后处死大鼠,提取新鲜脊髓组织行RT-PCR,检测SRp30c mRNA表达,分析其与疗效的关系。结果SRp30c在各组均有表达,大、小剂量组SRp30c mRNA表达明显高于模型组、正常对照组,差异有显著性;不同大鼠Kono评分改善的差值与其SRp30c mRNA表达值呈负相关(r=-0.583,P<0.05)。结论SRp30c表达与病情及MP剂量无直接关系,但与疗效呈负相关,表明其与糖皮质激素敏感性下降有着密切的关系,EAE模型发生激素抵抗的机制中SRp30c扮演着重要的角色。

Objective To investigate the expression of alternative splicing factor SRp30c and the therapeutic effect of methylprednisolone （MP） and the correlation between SRp30c and the therapeutic effect in experimental allergic encephalomyelitis （EAE） in rats after treatment with MP at different doses,and to explore the possible mechanisms of glucocortieoid resistance. Methods Established EAE model with Wistar rats and the animal model were divided into three groups （ high-dose group, low-dose group, and model control group）. High-dose group and low-dose group were treated by intravenous injection MP through caudal vein at the doses of 100 mg/ kg and 25 mg/kg respectively. Model control group and another normal control group were administered with normal saline at the same volume. The rats were executed after 5-day therapy, then the spinal cord was extracted and used to detect the expression of SRp30c mRNA by reverse transcription polymerase chain reaction. The relationship between SRp30c and the therapeutic effect was studied. Results SRp30c was expressed in every group. The expression level of high-dose group and low-dose group were significant higher than that of model and normal control group. There was linear correlation between the expression of SRp30c mRNA and the GN score changes （ r = - 0. 583, P 〈 0. 05 ）. Conclusion There was neither direct correlation between the expression of SRp30c and pathogenesis, nor the dose of MP. While it had a negative correlation between SRp30c and therapeutic effect. Therefore, it suggested that SRp30c contributed to the declining sensitivity of glueocorticoid, and it might play an important role in the mechanisms of glucoeorticoid resistance in EAE.