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| 选择性雌激素受体调节剂对实验性自身免疫性脑脊髓炎小鼠的抗炎机制研究 |
| 胡晓1,娄磊2,袁军3,万兴4,王建怡5,,秦新月1* |
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| (1.重庆医科大学附属第一医院神经内科,重庆 400016;2.遵义医学院小儿内科,遵义 563003;3.贵州省人民医院中心实验室,贵阳 550002;4.贵州省人民医院肿瘤科,贵阳 550002;5.贵州省人民医院小儿内科,贵阳 550002) |
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| 摘要: |
| 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、luxol fast blue(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。 |
| 关键词: 实验性自身免疫性脑脊髓炎 选择性雌激素受体调节剂 炎症 |
| DOI：10.3724/SP.J.1008.2010.00 |
| 投稿时间：2010-03-24修订日期：2010-08-31 |
| 基金项目:贵州省科技厅攻关项目\[黔科合sy(2009)3054\]. |
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| Anti-inflammatory mechanism of selective estrogen receptor modulator in mice with experimental autoimmune encephalomyelitis |
| HU Xiao1, LOU Lei2, YUAN Jun3, WAN Xing4, WANG Jian-yi5,,QIN Xin-yue1* |
| (1. Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;2. Department of Pediatrics, Zunyi Medical College, Zunyi 563003, Guizhou, China;3. Department of Central Laboratory, the Guizhou Provinical People’s Hospital, Guiyang 550002, Guizhou, China;4. Department of Oncology, the Guizhou Provinical People’s Hospital, Guiyang 550002, Guizhou, China;5. Department of Pediatrics, the Guizhou Provinical People’s Hospital, Guiyang 550002, Guizhou, China) |
| Abstract: |
| Objective To explore the anti-inflammatory mechanisms of selective estrogen receptor modulator (SERM) on experimental autoimmune encephalomyelitis(EAE). Methods EAE models were induced with MOG35-55 peptide in 60 mice and all animals were ovarectomized. The model animals were then divided into treatment group and control group (n=30). Treatment group was treated with SERM. The clinical symptom scores were compared between the two groups. The pathologic changes of the brain and spinal cord were studied by H-E staining and luxol fast blue(LFB)-HE staining. The expressions of MMP-9, TNF-α, IFN-γ, and IL-4 mRNA and protein were examined by quantitative real-time PCR and ELISA. Western blotting analysis was used to analyze the expression of myelin basic protein (MBP) so as to analyze the demyelination status.Results Clinical symptom scores and incidence of EAE in the treatment group were improved compared with those in the control group (P<0.01, P<0.05). H-E staining showed that infiltration of inflammatory cells was decreased in the treatment group (P<0.05). LFB-H-E staining and Western blotting analysis showed that the demyelination was improved in the treatment group (P<0.05). The results of quantitative real-time PCR and ELISA showed that the expression of MMP-9,TNF-α, and IFN-γ were decreased and the expression of IL-4 was increased (P<0.05, P<0.01). Conclusion SERM can alleviate the inflammation symptom in EAE mice through decreasing MMP-9, TNF-α, and IFN-γ and increasing IL-4 expression. |
| Key words: experimental autoimmune encephalomyelitis selective estrogen receptor modulators inflammation |
