| 李庆彬,岳振东,赵 博,刘言祥,张根明.姜黄素调节BDNF/TrkB信号通路对细菌性脑膜炎新生大鼠神经元凋亡的影响[J].,2024,(8):1411-1417 |
| 姜黄素调节BDNF/TrkB信号通路对细菌性脑膜炎新生大鼠神经元凋亡的影响 |
| Impact of Curcumin Regulating BDNF/TrkB Signaling Pathway on Neuronal Apoptosis in Neonatal Rat with Bacterial Meningitis |
| 投稿时间：2023-10-23 修订日期：2023-11-18 |
| DOI：10.13241/j.cnki.pmb.2024.08.002 |
| 中文关键词: 姜黄素 BDNF/TrkB信号通路 细菌性脑膜炎 神经元 凋亡 |
| 英文关键词: Curcumin BDNF/TrkB signaling pathway Bacterial meningitis Neuronal Apoptosis |
| 基金项目:北京中医药大学校级课题（2016-JYB-JSPY-016）；国家中医药管理局国家中医临床研究基地业务建设科研专项课题（JDZX2015050） |
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| 中文摘要: |
| 摘要 目的：探讨姜黄素（Cur）调节脑源性神经营养因子（BDNF）/原肌球蛋白相关激酶B受体（TrkB）信号通路对细菌性脑膜炎（BM）新生大鼠神经元凋亡的影响。方法：随机选择15只大鼠作为非感染组（NF组），其它大鼠通过额蛛网膜下腔注射肺炎链球菌ATCC49619菌悬液构建BM大鼠模型，将构建成功的BM模型随机平分为BM组、L-Cur组(1.25 mg/kg）、M-Cur组(2.5 mg/kg）、H-Cur组(5 mg/kg）、H-Cur+K252a组（5 mg/kg Cur+2.5 μg/kg K252a），每组15只大鼠，每天一次，连续注射3周。对大鼠称量体重并进行临床评分，HE染色以及尼氏染色观察神经细胞损伤；TUNEL染色评估神经元凋亡情况。免疫荧光染色检测神经胶质纤维酸性蛋白（GFAP）、脊髓钙离子接头蛋白-1（IBA-1）水平。实时荧光定量聚合酶链式反应（qRT-PCR）检测脑组织炎症因子和趋化因子水平。蛋白质印迹法（Western blot）检测脑组织凋亡蛋白以及BDNF/TrkB通路蛋白表达。结果：NF组脑组织结构正常，神经元胞质内出现大面积蓝色尼氏体。BM组蛛网膜下腔出现大量炎性渗出液和炎性细胞浸润现象，胞体增大，突起收缩，形态不规则；尼氏体数目、体重、Bcl-2、BDNF、p-TrkB/TrkB蛋白水平显著下降（P<0.05），临床评分、IBA-1、GFAP相对荧光强度值、趋化因子配体-2（CCL-2）、趋化因子配体-3（CCL-3）、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）的相对表达量、神经细胞凋亡率、BCL2-Associated X蛋白（Bax）蛋白水平显著升高（P<0.05）。Cur处理后各组脑组织炎性渗出液和细胞浸润现象减轻，尼氏体数目、体重、B淋巴细胞瘤-2基因（Bcl-2）、BDNF、p-TrkB/TrkB蛋白水平显著升高（P<0.05），临床评分、IBA-1、GFAP相对荧光强度值、CCL-2、CCL-3、TNF-α、IL-6的相对表达量、神经细胞凋亡率、Bax蛋白水平显著下降（P<0.05），且Cur添加剂量越高，变化越显著；H-Cur+K252a组与BM组效果相似，K252a逆转了Cur对BM大鼠神经元凋亡及损伤的改善作用。结论：Cur可能通过激活BDNF/TrkB信号通路降低BM大鼠神经元凋亡。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the impact of curcumin (Cur) regulating the brain-derived neurotrophic factor (BDNF)/tropomyosin related kinase B receptor (TrkB) signaling pathway on neuronal apoptosis in neonatal rat with bacterial meningitis (BM). Methods: 15 rats were randomly selected as non-infected group (NF group), other rats injected streptococcus pneumoniae ATCC49619 suspension into frontal subarachnoid space to construct BM rat model, the successful BM model was randomly divided into BM group, L-Cur group (1.25 mg/kg), M-Cur group (2.5 mg/kg), H-Cur group (5 mg/kg), H-Cur+K252a group (5 mg/kg Cur+2.5 μg/kg K252a), 15 rats in each group, once a day, the injections were given continuously for 3 weeks. The rats were weighed and clinical scored, HE staining and Nissl staining were used to observe the damage of nerve cells; TUNEL staining was used to evaluate neuronal apoptosis. The levels of glial fibrillary acid protein (GFAP) and spinal cord calcium ion adaptor protein-1 (IBA-1) were detected by immunofluorescence staining. The levels of inflammatory factors and chemokines in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Western blot was used to detect the expression of apoptosis protein and BDNF/TrkB pathway protein in brain tissue. Results: The brain tissue structure of the NF group was normal, large area of blue Nissl bodies appeared in the cytoplasm of neurons. In the BM group, a large amount of inflammatory exudate and inflammatory cell infiltration appeared in the subarachnoid space, the cell bodies were enlarged, the processes contracted, and the morphology was irregular; the number of Nissl bodies, weight, the levels of Bcl-2, BDNF, and p-TrkB/TrkB protein decreased obviously (P<0.05), the clinical score, the relative fluorescence intensity values of IBA-1 and GFAP, the relative expression of chemokine ligand-2 (CCL-2), chemokine ligand-3 (CCL-3), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), the rate of neuronal apoptosis, and the level of BCL2-Associated X protein (Bax) protein increased obviously (P<0.05). The inflammatory exudate and cell infiltration of brain tissue were reduced, the number of Nissl bodies, weight, the levels of B-lymphoblastoma-2 gene (Bcl-2), BDNF, and p-TrkB/TrkB protein increased obviously in each group after Cur treatment (P<0.05), the clinical score, the relative fluorescence intensity values of IBA-1 and GFAP, the relative expression of CCL-2, CCL-3, TNF-α, and IL-6, the rate of neuronal apoptosis, and the level of Bax protein decreased obviously (P<0.05), the higher the addition dose of Cur, the more obvious the change; the effect of H-Cur+K252a group was similar to that of BM group, K252a reversed the improvement effects of Cur on neuron apoptosis and damage in BM rat. Conclusion: Cur might reduced neuronal apoptosis in BM rat by activating BDNF/TrkB signaling pathway. |
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