β-榄香烯对自身免疫性脑脊髓炎小鼠早期炎性损伤的治疗作用及其免疫学机制  

The effect and immunological mechanism of β-elemene on the early inflammation in EAE mice

作　　者：张荣伟[1] 李颖[1] 田阿勇[2] 张慧敏[1] 禹红梅[3] 

机构地区：[1]中国医科大学干诊神经科,辽宁沈阳110001 [2]中国医科大学麻醉科,辽宁沈阳110001 [3]中国医科大学神经内科,辽宁沈阳110001

出　　处：《解剖科学进展》2012年第3期242-246,共5页Progress of Anatomical Sciences

基　　金：国家自然科学基金资助项目(No.81100889);辽宁省博士科研启动基金资助(No.20111106)

摘　　要：目的探讨β-榄香烯对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)小鼠早期炎性损伤的治疗作用及可能的免疫学机制。方法 6～8周龄健康雌性野生型C57BL/6小鼠(SPF15)共64只,均分为对照组、模型组和β-榄香烯治疗组。采用髓鞘少突胶质细胞糖蛋白(myelinoligodendrocyte glycoprotein peptide35-55,MOG35-55)多肽作为抗原诱发EAE小鼠模型。于免疫后15日剥离脊髓组织进行病理学研究,MTT实验检测EAE小鼠MOG抗原特异性增殖反应及β-榄香烯(β-elemene)对MOG抗原特异性增殖反应的影响,定量PCR技术分别检测各组小鼠脊髓及淋巴结细胞白细胞介素17(interleukin-17,IL-17)、转录因子孤儿核受体(retinoid acid-related orphan receptors-γt,RORγt)、白细胞介素6(interleukin-6,IL-6)、白细胞介素23(interleukin-23,IL-23)、转化生长因子β(transforming growth factor-β,TGF-β)以及叉头蛋白3(Foxp3)的mRNA的表达。结果模型组的神经功能评分高于治疗组(<0.05),治疗组小鼠脊髓炎症及轴索损伤较模型组减轻。免疫后11d,与模型组比较,治疗组小鼠脊髓IL-17、RORγt、IL-6、IL-23的mRNA的表达减少(<0.05),Foxp3mRNA的表达增加(<0.05),并持续至免疫后15d。体外研究发现模型组T淋巴细胞增殖较对照组更明显(<0.05),治疗组β-榄香烯对T淋巴细胞增殖抑制呈现明显的量效关系(<0.05);与模型组比较,治疗组体外培养的淋巴细胞IL-17、RORγt、IL-6、IL-23mRNA表达水平增加,Foxp3mRNA表达水平减少(<0.05)。结论β-榄香烯减轻EAE小鼠早期炎性损伤,可能与其抑制髓鞘少突胶质细胞糖蛋白多肽反应性T细胞的激活以及维持Th17细胞/调节T细胞亚群的平衡密切相关。Objective To study the neuroprotective effect of β-elemene on the early inflammation of experimental autoimmune encephalomyelitis（EAE） mice and its potential immunological mechanism.Methods 64 Female C57BL/6 mice（6~8w） were divided averagely into normal control group,EAE model（immunized with p35-55 peptide of myelin oligodendrocyte glycoprotein peptide35-55,MOG35-55） and β-elemene treated group.Mice were examined daily for neurological signs,spinal cords were removed at 15 days after immunization for pathologic study.Proliferation of lymphocytes was detected by MTT,mRNA expressions of IL-17,RORγt,IL-6,IL-23,TGF-β and Foxp3 were determined by real time PCR.Results Compared with the model group,the neurologic function and spinal cords inflammation and axonal damage were improved in β-elemene treated group（0.05）,and the expression levels of IL-17,RORγt,IL-6,IL-23 mRNA in spinal cords and lymphocytes declined,but increased for Foxp3 mRNA at 11 and 15 days（0.05）.β-elemene inhibited the proliferation of specific T lymphocytes dose-dependently（0.05）.Conclusion The repairment of β-elemene on EAE mice might be related to the inhibition and regulation of T lymphocytes by β-elemene in EAE mice.

关 键 词：Β-榄香烯 实验性自身免疫性脑脊髓炎 Th17细胞 调节T细胞 小鼠 

分 类 号：R744.3[医药卫生—神经病学与精神病学]