摘要
目的探讨2-甲氧基雌二醇(2ME2)对脊髓损伤大鼠运动功能及Tau蛋白磷酸化的影响。方法成年雄性SD大鼠72只按随机数字表法分为假手术组、脊髓损伤组和2ME2治疗组,每组24只。后2组大鼠采用改良的Allen’s法制作脊髓损伤大鼠模型。造模后1d 2ME2治疗组大鼠腹腔注射2ME2(24mg/kg),连续7d。脊髓损伤组大鼠注射等剂量生理盐水,假手术组不予干预。造模后1、3、7、14、21、28d应用BBB评分法对各组大鼠的后肢功能进行评分。造模后7d应用免疫荧光染色和Western blotting检测损伤脊髓磷酸化Tau蛋白(p-Tau)的表达。结果脊髓损伤组和2ME2治疗组大鼠脊髓损伤后1-28d随着时间的延长BBB评分升高,差异有统计学意义(P〈0.05)。损伤后7、14、21、28d2ME2治疗组大鼠BBB评分明显高于脊髓损伤组.差异有统计学意义(P〈0.05);与假手术组比较,脊髓损伤组和2ME2治疗组大鼠脊髓p-Tau阳性细胞数、蛋白表达均增加,且2ME2治疗组p-Tau阳性细胞数、蛋白表达(19.05±1.34、0.283±0.0941明显少于脊髓损伤组(10.36±1.28、0.607±0.105),差异均有统计学意义(P〈0.05)。结论2ME2可改善脊髓损伤大鼠的运动功能,具有一定的神经保护作用,其可能通过降低Tau蛋白磷酸化水平来实现。
Objective To investigate the effect of 2-methoxyestradiol (2ME2) on phosphorylation of Tau protein (p-Tau) and mortor function of rats after spinal cord injury (SCI). Methods A total of 72 adult male Sprague-Dawley rats were randomly divided into 3 groups: sham-operated group (n=24), SCI group (n=24) and SCI+2ME2 treated group (n=24); models of SCI were created by modified Alien's method; one d after SCI, rats in the SCI+2ME2 treated group were given intraperitoneal injection of 2ME2 (24 mg/kg) for seven d, and rats in the SCI group were given the same volume of normal saline. Basso, Beatti, Bresnahan (BBB) scale was performed to evaluate the hindlimb function one, three, seven, 14, 21 and 28 d after SCI; the expression changes of p-Tau (Ser 262) seven d after SCI were observed by immunofluorescence and Western blotting. Results BBB scale scores in the SCI group and SCI+2ME2 group were significantly increased following the prolonging of injury times (I-28 d of injury, P〈0.05); on the 7^th, 14^th, 21^st and 284 d of injury, the scores in the SCI+2ME2 group were significantly higher than those in the SCI group (P〈0.05). The p-Tau positive cells in the spinal cord and the p-Tau (Ser 262) expression in the SCI group and SCI+2ME2 group were significantly increased as compared with those in the sham-operated group (P〈0.05), and those in the SCI+2ME2 group (19.05±1.34 and 0.283±0.094) were obviously lower as compared with those in the SCI group (10.36±1,28 and 0.607±0.105, P〈0.05), Conclusion 2ME2 offers protection in rats with SCI by reducing the level of tau phosphorylation.
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2014年第11期1127-1130,共4页
Chinese Journal of Neuromedicine
基金
国家临床重点建设专科资助项目
广东省神经外科临床中心资助项目