雌二醇对大鼠EAE血-脑脊液屏障及TGF-β表达的作用

The Effect of Estradiol on Blood Cerebrospinal Fluid Barrier and Transforming Growth Factor-β in Wistar Rats with Experimental Autoimmune Encephalomyelitis

目的：探讨雌二醇（E2）对大鼠实验性自身免疫性脑脊髓炎（EAE）血脑屏障及转化生长因子-β（TGF-β）表达的作用。方法制作摘卵巢后10d的大鼠EAE模型，随机分成E2组、EAE组、佐剂对照组。E2组自免疫后（p.i.）0～8d每日肌注E2一次。测定各组于不同时间的症状评分、E2浓度、脑脊液与血清白蛋白含量的比值（QA），依据QA评估血-脑脊液屏障（BCB）的破坏。在p.i.8～17d取脑和脊髓做髓鞘染色；应用免疫组化的方法测量各组TGF-β的表达。结果p.i.8～14dE2组血清E2浓度较EAE组升高；症状评分E2组低于EAE组；发病率E2组低于EAE组；P.i.8～17dE2组QA峰值低且出现时间较EAE组推迟；P.i.8～17dE2组TGF-β表达较EAE组增高。结论E2能够有效抑制EAE，其抑制机制与E2保护BCB的结构和功能，以及增加TGF-β的表达有关。

Objective To study the immunosuppressive effect of estradiol（E2）and its mechanism in ovariectomized rats with experimental autoimmune encephalomyelitis （EAE）. Methods Wister rats which were ovariectomized ten days were randomly divided into E2 group, EAE group and Complete Freund Adjuvant （CFA） group. E2 group were injected with E2 once a day from 0 to 8 p.i.. The clinical symptom, the serum E2 level and CSF to serum albumin quotient （QA） were detected at different times. The damage of the blood-cerebrospinal fluid barrier（BCB）was evaluated by QA. The brain and spinal cords were removed on day from 8 to 17 p.i. for Luxol Fast Blue staining and immunohistochemical staining to the expression of transforming growth factor-β（TGF-β）. Results When compared with EAE group,the serum E2 level in E2 group increased obviously on days from 8 to 14 p.i. When compared with EAE group（2.76＆#177;1.18）,the clinical symptom of E2 group （0.44＆#177;0.58） was statistically significantly decreased . The incidence in E2 group was statistically significantly decreased when compared with EAE group. The QA value in EAE group rapidly increased to the peak on day 8p.i., but slowly increased to the peak on day 14p.i. in E2 group. The difference was statistically significant . The differences of average photodensity were statistically between EAE group and E2 group from on days from 8 to 17 p.i. Our results suggest that the expression of TGF-βin E2 group was obviously higher than that in EAE group. Conclusions E2 is a potential agent to inhibit EAE effectively. The inhibiting mechanism of E2 is related to up-regulation of TGF-β, which may protect BCB from the damage of inflammation.