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目的探讨选择性雌激素受体调节剂(SERM)减轻实验性自身免疫性脑脊髓炎(EAE)炎症反应的可能机制。方法用MOG35-55多肽诱发60只EAE小鼠模型,做去卵巢术。分为治疗组和对照组(n=30),治疗组予SERM(雷洛昔芬)治疗。比较2组EAE小鼠的临床症状评分。取脑和脊髓组织,行H-E染色、luxolfastblue(LFB)-H-E染色观察病理学改变;实时荧光定量PCR及ELISA法检测基质金属蛋白酶9(MMP-9)、肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)、白细胞介素4(IL-4)水平;蛋白质印迹分析检测髓鞘碱性蛋白(MBP)表达量,分析脱髓鞘情况。结果治疗组EAE小鼠与对照组相比,治疗组临床症状减轻(P<0.01)、发病率降低(P<0.05);H-E染色显示治疗组炎细胞浸润减少(P<0.05);LFB-H-E染色结果和MBP表达量显示治疗组脱髓鞘减轻(P<0.05);实时荧光定量PCR及ELISA结果示治疗组脑和脊髓组织中MMP-9、TNF-α、IFN-γ表达降低而IL-4增加(P<0.05,P<0.01)。结论 SERM可能通过降低MMP-9、TNF-α、IFN-γ表达,增加IL-4表达,从而减轻EAE小鼠炎症反应。
Objective To investigate the possible mechanism of selective estrogen receptor modulator (SERM) in reducing inflammation in experimental autoimmune encephalomyelitis (EAE). Methods Sixty EAE mouse models were induced with MOG35-55 peptide to perform ovariectomy. Divided into the treatment group and the control group (n = 30), the treatment group to SERM (raloxifene) treatment. The clinical symptom scores of two groups of EAE mice were compared. The brain and spinal cord tissues were taken out and stained with hematoxylin and eosin (HE). Luxolfastblue (LFB) -HE staining was used to observe the pathological changes. The expressions of MMP-9, TNF- Interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels were measured. Western blot analysis was performed to detect the expression of MBP, and the demyelination was analyzed. Results Compared with the control group, the clinical symptoms of the EAE mice in the treatment group were alleviated (P <0.01), and the morbidity was decreased (P <0.05). The number of inflammatory cells in the treatment group was decreased (P <0.05) The results of staining and MBP showed that the demyelination was relieved in the treatment group (P <0.05). The results of real-time fluorescence quantitative PCR and ELISA showed that the expression of MMP-9, TNF-α and IFN- 4 increased (P <0.05, P <0.01). Conclusion SERM may reduce the inflammatory response of EAE mice by decreasing the expression of MMP-9, TNF-α and IFN-γ and increasing the expression of IL-4.