Shi Yu, Wang Bao-Jun, Chen Chao, Pang Jiang-Xia, Li Yang, Zhang Jun, Xu Mao-Mao
Central Clinical Medical College of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou,Nei Mongol 014040,China.
Department of Neurology,Baotou Central Hospital,Baotou,Nei Mongol 014040,China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2024 Oct;46(5):659-665. doi: 10.3881/j.issn.1000-503X.16017.
Objective To explore the mechanism of butylphthalide (NBP) in regulating microglia activation and inflammatory cytokine expression in the hippocampus of the mouse model of delayed encephalopathy after carbon monoxide poisoning (DEACMP). Methods Wild-type C57 adult mice with normal cognitive function were selected,and DEACMP was modeled by static inhalation of carbon monoxide.The mice were randomized into three groups:DEACMP,control,and NBP.The NBP group was administrated with NBP suspension at 6 mg/kg by gavage for 21 days,and the DEACMP and control groups were administrated with the same amount of vegetable oil by gavage.The hippocampal injury was observed by HE staining.The protein level of ionized calcium-binding adapter molecule 1 (IBA1) was determined by Western blotting,and the levels of downstream inflammatory cytokines were measured by ELISA. Results Compared with the control group,the DEACMP and NBP groups showed prolonged escape latency (=0.001,=0.029),reduced nerve cells (=0.001,=0.035),up-regulated expression of IBA1 (=0.001,=0.042),increased mean fluorescence intensity of IBA1 (=0.001,=0.021),and elevated levels of tumor necrosis factor-α (TNF-α) (=0.002,=0.024),interleukin (IL)-6 (=0.001,=0.015),and IL-1β (=0.001,=0.023).Compared with the DEACMP group,the NBP group showed shortened escape latency (=0.025),increased nerve cells (=0.039),down-regulated expression of IBA1 (=0.035),decreased average fluorescence intensity of IBA1 (=0.031),and lowered levels of TNF-α (=0.028),IL-6 (=0.037),and IL-1β (=0.034). Conclusion NBP can inhibit the activation of microglia and reduce the expression of inflammatory factors,thereby alleviating cognitive dysfunction and brain tissue damage caused by DEACMP.
目的 探讨丁苯酞（NBP）对一氧化碳中毒迟发性脑病（DEACMP）小鼠模型海马区小胶质细胞激活及炎性细胞因子表达的调控机制。方法 选取认知功能正常的野生型C57成年小鼠，通过静态吸入一氧化碳建立DEACMP模型。将小鼠随机分为三组：DEACMP组、对照组和NBP组。NBP组给予6 mg/kg NBP混悬液灌胃21天，DEACMP组和对照组给予等量植物油灌胃。通过HE染色观察海马损伤情况。采用蛋白质免疫印迹法检测离子钙结合衔接分子1（IBA1）蛋白水平，采用酶联免疫吸附测定法检测下游炎性细胞因子水平。结果 与对照组相比，DEACMP组和NBP组逃避潜伏期延长（P=0.001，P=0.029），神经细胞减少（P=0.001，P=0.035），IBA1表达上调（P=0.001，P=0.042），IBA1平均荧光强度增加（P=0.001，P=0.021），肿瘤坏死因子-α（TNF-α）水平升高（P=0.002，P=0.024）、白细胞介素（IL）-6水平升高（P=0.001，P=0.015）、IL-1β水平升高（P=0.001，P=0.023）。与DEACMP组相比，NBP组逃避潜伏期缩短（P=0.025），神经细胞增加（P=0.039），IBA1表达下调（P=0.035），IBA1平均荧光强度降低（P=0.031），TNF-α水平降低（P=0.028）、IL-6水平降低（P=0.037）、IL-1β水平降低（P=0.034）。结论 NBP可抑制小胶质细胞激活，降低炎性因子表达，从而减轻DEACMP所致的认知功能障碍和脑组织损伤。
