| 李 楠,张二飞,张 静,阴弯弯,张 莉,闫如虎,金红旭,高 燕,侯立朝.重组人脑利钠肽对脓毒症相关性脑病小鼠神经细胞凋亡的治疗作用[J].,2020,(7):1217-1223 |
| 重组人脑利钠肽对脓毒症相关性脑病小鼠神经细胞凋亡的治疗作用 |
| Therapeutic Effects of Recombinant Human Brain Natriuretic Peptide on Neuronal Apoptosis of Mice with Sepsis-associated Encephalopathy |
| 投稿时间：2019-11-23 修订日期：2019-12-18 |
| DOI：10.13241/j.cnki.pmb.2020.07.004 |
| 中文关键词: 脓毒症相关性脑病 认知功能障碍 重组人脑利钠肽 炎症反应 凋亡 |
| 英文关键词: Sepsis-associated encephalopathy Cognitive dysfunction Recombinant human brain natriuretic peptide Inflammatory response Apoptosis |
| 基金项目:国家自然科学基金项目(81171839)；陕西省科学技术研究发展计划项目(2016YFJH2-04) |
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| 中文摘要: |
| 摘要 目的：探讨重组人脑利钠肽(recombinant human brain natriuretic peptide, rhBNP)对脓毒症小鼠脑病理损伤和认知功能障碍的治疗效应，明确其脑保护作用机制。方法：采用盲肠结扎穿刺法(Cecal ligation and puncture, CLP)建立脓毒症小鼠模型。在CLP手术后6小时皮下注射rhBNP，相同容积的生理盐水被作为对照，连续14天，每日一次。通过旷场实验，评价动物基础运动状态、探索能力和焦虑情绪；采用条件相关恐惧实验，检测动物情景相关记忆能力变化。TUNEL染色检测动物海马CA1区神经细胞凋亡变化；蛋白质免疫印迹法(Western blot, WB)检测动物海马组织TNF-?琢、Caspase-8和Caspase-3蛋白表达水平变化。结果：在旷场实验中，与Sham+Veh组小鼠相比较，CLP+Veh组小鼠表现出平均运动速度（P<0.0001）、5分钟穿格次数（P<0.0001）和中央区域运动时间明显下降（P<0.0001）。与CLP+Veh组小鼠相比较，CLP+rhBNP组小鼠旷场中平均运动速度（P=0.35）和5分钟穿格次数（P=0.064）无显著变化，中央区域运动时间明显增加（P=0.0005）。在条件相关恐惧测试中，与Sham+Veh组小鼠相比较，CLP+Veh组小鼠表现为僵直时间比例明显减少（P<0.0001）。与CLP+Veh组小鼠相比较，CLP+rhBNP组小鼠表现为僵直时间比例显著增加（P=0.0014）。CLP诱导的脓毒症小鼠表现出海马CA1区神经细胞凋亡。rhBNP治疗可以明显的减轻脑病理变化，并且通过抑制Caspase-3上游信号通路TNF-a-Caspase-8减轻神经细胞凋亡。结论：rhBNP对SAE具有治疗作用，其机制可能与抑制神经细胞凋亡有关。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the therapeutic effect of recombinant human brain natriuretic peptide on pathological brain injury and cognitive dysfunction in septic mice, and to clarify its mechanism of brain protection. Methods: The cecum ligation puncture method (CLP) septic mice model was established. rhBNP was injected subcutaneously 6 hours after CLP surgery, and the same volume of saline was used as a control for 14 days, once daily. The basic motion state, exploration ability and anxiety of animals were evaluated by open-field experiment. The conditional fear test was used to detect the changes in the contextual memory of animals. TUNEL staining was used to detect the apoptosis of nerve cells in CA1 region of hippocampus. Western blotting was used to detect the expression levels of TNF-α, caspase-8 and caspase-3 in hippocampal tissues. Results: In the open-field test, the mice in the CLP+Veh group had a significant decrease in average movement speed(P<0.0001), the number of line crossing within 5 min(P<0.0001), and the movement time in the central region (P<0.0001) when compared with that in the Sham+Veh group. There were no statistically significant differences in average movement speed (P=0.35) and the number of line crossing within 5 min (P=0.064) after rhBNP treatment in the CLP+rhBNP group, but the movement time in the central region was significantly increased(P=0.0005) when compared with that in the CLP+Veh group. In the condition-related fear test, the percentage of freezing time of mice in the CLP+Veh group was significantly reduced when compared with that in the Sham+Veh group(P<0.0001). The percentage of freezing time of mice in the CLP+rhBNP group was significantly increased when compared with that in mice from CLP+Veh group(P=0.0014). CLP-induced septic mice showed neuronal apoptosis of hippocampal CA1 region. rhBNP therapy can significantly reduce brain pathological changes and reduce neuronal apoptosis by inhibiting the TNF-a- caspase-8 signaling pathway upstream of caspase-3. Conclusion: Therefore, The mechanism of rhBNP treatment for SAE may be related to inhibition of neuronal apoptosis. |
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