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目的探讨雌二醇(E2)对去卵巢后实验性自身免疫性脑脊髓炎(EAE)大鼠的免疫抑制作用及其机制。方法制备去卵巢后10d的EAE动物模型,随机分为EAE组、E2治疗组和佐剂对照组。E2治疗组于免疫后(pi)0～8d肌注E2(250μg/kg)1次/d。观察各组在不同时间点的临床症状、血清E2浓度、血清和脑脊液中白蛋白含量比值(QA),通过QA评定血脑屏障(BBB)的损害。在p i8、11、14、17d处死动物并取脑和脊髓,行HE和髓鞘染色;采用Western blot检测各组基质金属蛋白酶-9(MMP-9)的表达。结果 E2治疗组临床症状评分(0.46±0.62)较EAE组(2.88±1.26)降低(t=2.11,P<0.05);E2治疗组发病率(20%)较EAE组(80%)降低(χ2=6.24,P<0.05)。pi 8～14dE2治疗组血清E2浓度较EAE组升高(F=1 532.63,P<0.05)。pi 8～17dE2治疗组QA峰值低且出现时间较EAE组延迟(0.36±0.04 vs 0.18±0.03,F=26.20,P<0.05)。E2治疗组MMP-9表达较EAE组明显下调(F=21.46,P<0.05)。结论 E2能够有效抑制EAE,其抑制机制与E2下调MMP-9的表达进而保护BBB的结构和功能有关。
Objective To investigate the immunosuppressive effects of estradiol (E2) on experimental autoimmune encephalomyelitis (EAE) rats after ovariectomy and its mechanism. Methods EAE animal models of ovariectomized 10 days were randomly divided into EAE group, E2 treatment group and adjuvant control group. E2 treatment group at 0 ~ 8d after immunization (pi) intramuscular E2 (250μg / kg) 1 time / d. The clinical symptoms, serum E2 concentration, albumin content ratio (QA) in serum and cerebrospinal fluid of each group were observed at different time points, and the damage of the blood-brain barrier (BBB) was evaluated by QA. The animals were sacrificed on day 8, 11, 14 and 17, and the brain and spinal cord were harvested for HE and myelin staining. The expression of matrix metalloproteinase-9 (MMP-9) was detected by Western blot. Results The score of clinical symptom in E2 group was significantly lower than that in EAE group (0.46 ± 0.62 vs 2.88 ± 1.26, t = 2.11, P <0.05). The incidence of E2 in treatment group (20%) was lower than that in EAE group = 6.24, P <0.05). The level of serum E2 in pi 8 ~ 14dE2 treatment group was higher than that in EAE group (F = 1 532.63, P <0.05). The QA peak in pi 8-17dE2 group was lower than that in EAE group (0.36 ± 0.04 vs 0.18 ± 0.03, F = 26.20, P <0.05). The expression of MMP-9 in E2 group was significantly lower than that in EAE group (F = 21.46, P <0.05). Conclusion E2 can effectively inhibit EAE and its mechanism of inhibition is related to the down-regulation of MMP-9 expression by E2 and the protection of the structure and function of BBB.