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目的:探究骨髓间充质干细胞(BMSCs)尾静脉移植后对大鼠癫痫模型的免疫调节作用。方法:成年雄性SD大鼠60只随机分为假手术Sham组(n=20),模型Model组(n=20)和BMSCs组(n=20)。采用匹鲁卡品诱导癫痫模型,2 h后行GFP+BMSCs移植,14 d后免疫组化染色观察BMSCs分布情况,血脑屏障通透性衡量采用伊文思蓝染色,脑水肿程度观察采用脑水含量测定,高迁移率组蛋白1(HMGB1),肿瘤坏死因子α(TNF-α)和白介素1β(IL-1β)等炎症因子水平鉴定采用酶联免疫吸附试验(ELISA),超氧化物歧化酶(SOD),丙二醛(MDA)和过氧化氢酶(CAT)等氧化应激水平衡量采用酶活性测定的方法。结果:BMSCs成功分布到海马和附近皮层区域。BMSCs组相比Model组能够显著降低脑水肿(P<0.05),提升血脑屏障完整性(P<0.05),下调TNF-α,IL-1β和HMGB1等炎症因子水平(P<0.05),上调SOD和CAT的活性(P<0.05),减少MDA的产生(P<0.05)。结论:BMSCs移植有免疫调节作用,能够明显降低癫痫相关炎症反应。
Objective: To investigate the immunomodulatory effect of bone marrow mesenchymal stem cells (BMSCs) tail vein transplantation on rat epilepsy model. Methods: Sixty adult male Sprague-Dawley rats were randomly divided into Sham group (n = 20), model group (n = 20) and BMSCs group (n = 20). Pilocarpine induced epilepsy model, 2 h after GFP + BMSCs transplantation, 14 d after the observation of the distribution of BMSCs by immunohistochemistry, the permeability of the blood-brain barrier using Evans blue staining, the degree of cerebral edema was observed using brain water The level of inflammatory cytokines such as HMGB1, TNF-αand IL-1βwere detected by enzyme linked immunosorbent assay (ELISA), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) and other oxidative stress levels measured by enzyme activity determination method. RESULTS: BMSCs were successfully distributed in the hippocampus and nearby cortical areas. Compared with Model group, BMSCs could significantly reduce brain edema (P <0.05), enhance the integrity of blood-brain barrier (P <0.05) and down-regulate the levels of inflammatory cytokines such as TNF-α, IL-1βand HMGB1 SOD and CAT activity (P <0.05), reduce the production of MDA (P <0.05). Conclusion: BMSCs transplantation has immunomodulatory effect, which can significantly reduce epilepsy-related inflammatory reaction.