摘要
目的:探讨雌二醇(estradiol,E2)对去卵巢后实验性自身免疫性脑脊髓炎(Experimental autoimmune encephalomyeli-tis,EAE)大鼠的免疫抑制作用及其机制。方法:制备去卵巢后10天的EAE动物模型,随机分为EAE组、E2治疗组和佐剂组。E2治疗组从免疫后(Post-inoculation,p.i.)0~5天每日肌注E2(250μg/kg)一次。观察各组在不同时间点的血清E2浓度、血清和脑脊液中白蛋白含量比值(CSF to serum albumin quotient,QA),通过QA评定血脑屏障(Blood-brain barrier,BBB)的损害。在p.i.6、8、10、12、14、16天处死动物,取脑和脊髓用免疫组化技术检测不同部位细胞间粘附分子1(Intercellular adhension molecule-1,I-CAM-1)和干扰素γ(Interferon-γ,IFN-γ)的表达,并对EAE组ICAM-1和IFN-γ进行相关分析。结果:在p.i.6~12天E2治疗组血清E2浓度较EAE组升高(F=1666.49,P<0.05)。EAE组QA在p.i.8天达峰值(0.31±0.07),E2治疗组QA在p.i.14天达峰值(0.20±0.04),E2治疗组QA值幅度低且峰值出现时间较EAE组延迟(F=26.20,P<0.05)。E2治疗组临床症状评分(0.53±0.92)较EAE组(2.07±1.67)降低(t=2.93,P<0.05);E2治疗组体重减轻(6.73±3.53)较EAE组(15.40±4.03)减少(t=6.26,P<0.05);E2治疗组发病率(27%)较EAE组(73%)降低(χ2=6.53,P<0.05)。在p.i.10~16天,E2治疗组ICAM-1的表达较EAE组降低(F=21.01,P<0.05),E2治疗组IFN-γ的表达较EAE组降低(F=26.19,P<0.05)。EAE组ICAM-1与IFN-γ表达呈显著正相关性(r=0.87,P<0.01)。结论:E2能够有效抑制EAE,其抑制机制与E2下调ICAM-1、IFN-γ的表达,进而保护BBB的功能和促使Th细胞发生转分化有关。
Objective: To study the immunosuppressive effect of E2 and its mechanism in ovafiectomized rats with EAE. Methods: Wistar rats ovariectomized ten days ago were randomly divided into EAE group, E2 group and Complete Freund Adjuvant(CFA) group. E2 group were injected with E2(250 μg/kg) once a day from 0 to 5 p.i. Serum E2 was monitered with fall automatic chemiluminescence immune assay. Albumin of CSF and serum was quantified by full automatic biochemistry analyzer and damages of BBB were evaluated by the albumin QA of CSF to serum.The brain and spinal cords were removed on days from 6 to 16 p.i. for immunohistochemical staining of ICAM-1 and IFN-γ in different parts of the nervous system. Correlation in amounts of ICAM-1 to IFN-γ was analyzed with IMAGE systems. Results: When compared with EAE group, the serum E2 level in F2 group increased obviously on days from 6 to 12 p. i. ( F = 1666.49, P 〈 0.05). The QA value in EAE group rapidly increased to the peak(0.31±0.07) on day 8 p.i. ,but slowly increased to the peak(0.20_+ 0.04) on day 14 p.i.in E2 group. The difference was statistically significant ( F = 26.20, P 〈 0.05). When compared with EAE group(2.07±1.67 ), the score of clinical symptoms of E2 group(0.53±0.92) was significantly decreased( t = 2.93, P 〈 0.05)in E2 group.The loss of body weight and the incidence in E2 group was significantly decreased when compared with those of EAE group(6.73±3.53 vs 15.40±4.03, t = 6.26, P 〈 0.05; 27 % vs 73 %, X^2= 6.53, P 〈 0.05). On days 10 to 16 p. i, the expression of ICAM-1 and IFN-γ in E2 group were degraded ( F = 21.01, P 〈 0.05 ; F = 26.19, P 〈 0.05 respectively)when compared those of with EAE group. The expression of ICAM-1 and IFN-γ in EAE group was positively correlated( r = 0.87, P 〈 0.01 ) with each other. Conclusion: E2 is a potential agent to inhibit EAE effectively. The inhibiting mechanism of E2 is related to down-regulation of the expression of ICAM-1 and IFN-γ, which may not only protect BBB from damage of inflammation but also promote the transdifferentiation of Th cells.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2008年第11期997-1002,共6页
Chinese Journal of Immunology
基金
国家人口和计划生育委员会2005年科技立项(C1-42)
山西省2003年回国留学人员科研基金项目(2003-69)
山西省大同市2005年科技发展计划项目(2005-81)