| 杨珊,吴连连,郭雯,丁云鹤,董海北,吴小进.动物双歧杆菌BB-12改善全脑照射后小鼠海马神经炎症和认知功能障碍的研究[J].中华放射医学与防护杂志,2022,42(11):823-829 |
| 动物双歧杆菌BB-12改善全脑照射后小鼠海马神经炎症和认知功能障碍的研究 |
| Bifidobacterium animalis subsp. lactis BB-12 alleviates hippocampal neuroinflammation and cognitive dysfunction of mice after whole brain irradiation |
| 投稿时间：2022-06-21 |
| DOI：10.3760/cma.j.cn112271-20220621-00260 |
| 中文关键词: 放射性脑损伤 认知功能障碍 胶质细胞 神经炎症 动物双歧杆菌 |
| 英文关键词:Radiation induced brain injury Cognitive dysfunction Glial cell Neuroinflammation Bifidobacterium animalis subsp. lactis |
| 基金项目:吴阶平医学基金(320.6750.2021-13-3);徐州医科大学附属医院发展基金(XYFZ2020003) |
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| 中文摘要: |
| 目的 探讨动物双歧杆菌BB-12对全脑照射后小鼠海马神经炎症和认知功能的影响。方法 选取60只7~8周龄雄性C57BL/6J小鼠,采用完全随机法分为5组,每组12只,即健康对照组(Con组)、益生菌组(BB-12组)、单纯照射组(IR组)、照射+美金刚组(IR+Memantine组)、照射+益生菌组(IR+BB-12组)。采用医用直线加速器对小鼠行10 Gy电子线全脑照射建立放射性脑损伤模型。Y-迷宫实验评估小鼠认知功能;免疫荧光染色检测海马小胶质细胞和星形胶质细胞激活水平;实时荧光定量PCR技术(QRT-PCR)和蛋白免疫印迹(Western blot)检测海马炎症因子白介素1β(IL-1β)、IL-6和肿瘤坏死因子α(TNF-α)的表达水平。结果 Y-迷宫实验显示,与Con组相比,IR组小鼠到达新异臂的次数占3个臂总次数的百分比明显降低(t= 5.04,P<0.05);BB-12可以改善放射性脑损伤后小鼠认知障碍(t=4.72,P<0.05)。与Con组相比,IR组小鼠海马区Iba1、GFAP阳性细胞数量显著增多(t=3.05、7.18,P <0.05),圆形度指数显著升高(t=6.23、2.52,P<0.05),小胶质细胞和星形胶质细胞被激活;与IR组相比,IR+BB-12组小鼠海马区Iba1、GFAP阳性细胞数量减少(t=4.80、2.90,P<0.05),圆形度指数降低(t=6.22、2.63,P<0.05),BB-12可以抑制小胶质细胞和星形胶质细胞激活。IR组小鼠海马区炎症因子IL-1β、IL-6、TNF-α mRNA和蛋白表达水平显著升高(与Con组相比:tmRNA=4.10、3.04、4.18,P<0.05;t蛋白=11.49、7.04、8.42,P<0.05);BB-12可以降低受照后IL-1β、IL-6、TNF-α mRNA和蛋白的表达水平(与IR组相比:tmRNA=4.19、3.40、2.84,P<0.05;t蛋白=6.36、4.03、3.75,P<0.05)。结论 动物双歧杆菌BB-12可抑制照射后小鼠海马区小胶质细胞、星形胶质细胞介导的神经炎症,并改善放射性认知功能障碍,具有缓解放射性脑损伤的应用潜力。 |
| 英文摘要: |
| Objective To investigate the effects of Bifidobacterium animalis subsp. lactis BB-12 on hippocampal neuroinflammation and cognitive function of mice after whole brain radiotherapy.Methods A total of sixty male C57BL/6J mice aged 7-8 weeks were randomly divided into 5 groups with 12 mice in each group: control group (Con group), probiotic group (BB-12 group), irradiation group (IR group), irradiation and Memantine group (IR+Memantine group), irradiation and probiotic group (IR+BB-12 group). The model of radiation-induced brain injury of mice was established by 10 Gy whole brain radiotherapy with a medical linear accelerator. Y-maze test was used to evaluate the cognitive function. The activation of microglia and astrocytes was observed by immunofluorescence staining. The expressions of inflammatory cytokines interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were detected by quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR) and Western blot.Results Y-maze test showed that, compared with Con group, the percentage of the times of reaching the novel arm in the total times of the three arms decreased significantly in the IR group (t=5.04, P<0.05). BB-12 mitigated radiation-induced cognitive dysfunction (t=4.72, P<0.05). Compared with Con group, the number (t=3.05, 7.18, P<0.05) and circularity index (t=6.23, 2.52, P<0.05) of Iba1 and GFAP positive cells were increased, the microglia and astrocytes were activated in the hippocampus of IR group, but these alterations were eliminated by BB-12. After whole brain IR, the mRNA and protein expression levels of inflammatory cytokines IL-1β, IL-6 and TNF-α in the hippocampus of mice were significantly increased compared with Con group (tmRNA =4.10, 3.04, 4.18, P<0.05; tprotein=11.49, 7.04, 8.42, P<0.05), which were also significantly reduced by BB-12 compared with IR group (tmRNA=4.20, 3.40, 2.84, P<0.05; tprotein=6.36, 4.03, 3.75, P<0.05).Conclusions Bifidobacterium animalis BB-12 can suppress neuroinflammation mediated by microglia and astrocytes in the hippocampus of mice after radiotherapy and alleviates IR-induced cognitive dysfunction. Therefore, BB-12 has potential application in alleviating radiation induced brain injury. |
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