短链脂肪酸通过抑制颅脑创伤后小胶质细胞促炎作用减轻脑损伤  

Short-chain fatty acids attenuate brain injury by inhibiting the pro-inflammatory effects of microglia following traumatic brain injury

作　　者：张子文 王凯 王亭皓 王嘉辉 葛顺楠 屈延 ZHANG Ziwen;WANG Kai;WANG Tinghao;WANG Jiahui;GE Shunnan;QU Yan(Department of Neurosurgery,Tangdu Hospital,Air Force Medical University,Xi'an 710038,China;Department of Neurosurgery,The 902nd Hospital of the PLA Joint Logistic Support Force,Bengbu 233000,China)

机构地区：[1]空军军医大学唐都医院神经外科,陕西西安710038 [2]解放军联勤保障部队第九〇二医院神经外科,安徽蚌埠233000

出　　处：《空军军医大学学报》2025年第3期312-317,共6页Journal of Air Force Medical University

基　　金：国家自然科学基金(82130038)。

摘　　要：目的探究短链脂肪酸(SCFAs)对创伤性颅脑损伤(TBI)神经功能的保护作用,并解释其机制。方法随机将54只小鼠分为TBI+SCFAs组、TBI组和Sham组(n=18)。采用可控制皮质冲击法进行造模。造模成功后,TBI+SCFAs组每日给予100 mg/kg的SCFAs混合液进行灌胃,其余两组以相同的方式每日给予10 mg/kg的生理盐水,连续14 d。采用行为学实验评价小鼠神经功能缺陷;通过脑含水量测定评估小鼠脑水肿情况;免疫荧光及TUNEL法检测损伤周边小胶质细胞活化和凋亡分子;流式细胞术分离脑组织中小胶质细胞,qRT-PCR检测小胶质细胞中相关炎症因子转录水平;ELISA法测定损伤周围皮层组织炎症因子表达情况。结果与TBI组相比,TBI+SCFAs组TBI后小胶质细胞促炎作用减弱(P<0.01),神经元凋亡减少(P<0.05,P<0.01),炎症因子表达降低(P<0.01),脑水肿减轻(P<0.05,P<0.01),神经功能障碍明显改善。结论SCFAs可以通过抑制小胶质细胞的促炎作用来改善TBI后的神经功能障碍。Objective To explore the protective effect of short-chain fatty acids(SCFAs)on neurological function in traumatic brain injury(TBI)and explain its mechanism.Methods Fifty-four mice were randomly divided into TBI+SCFAs group,TBI group,and Sham group(n=18).The modeling was established using controlled cortical impact method.After successful modeling,the TBI+SCFAs group was given 100 mg/kg of SCFAs mixture by gavage every day,and the remaining two groups were given 10 mg/kg of normal saline in the same manner every day for 14 consecutive days.Behavioral experiments were used to evaluate the neurological deficits in mice.Brain edema of rats was assessed by brain water content measurement.Activation and apoptosis molecules of microglia around the injury were detected by immunofluorescence and TUNEL assay.Microglia were isolated from brain tissue by flow cytometry,and the transcript levels of relevant inflammatory factors in microglia were detected by qRT-PCR.The expression of inflammatory factors in cortical tissues around the injury was determined by ELISA.Result Compared with the TBI group,the TBI+SCFAs group exhibited a reduction in the pro-inflammatory effects of microglia(P<0.01),decreased neuronal apoptosis(P<0.05,P<0.01),reduced expression of inflammatory factors(P<0.01),alleviated brain edema(P<0.05,P<0.01),and significant improvement in neurological dysfunction after TBI.Conclusion SCFAs can improve neurological dysfunction after TBI by inhibiting the pro-inflammatory effects of microglia.

关 键 词：短链脂肪酸 创伤性颅脑损伤 小胶质细胞 肠道菌群代谢物 

分 类 号：R651.15[医药卫生—外科学]