[1]李张珂,马 涛,满明昊,等.辛伐他汀对创伤性脑损伤小鼠继发性炎症抑制作用及机制研究[J].陕西医学杂志,2022,51(11):1332-1336.[doi:DOI:10.3969/j.issn.1000-7377.2022.11.003]
　LI Zhangke,MA Tao,MAN Minghao,et al.Inhibitory effect and mechanism of simvastatin on secondary inflammation in mice with traumatic brain injury[J].,2022,51(11):1332-1336.[doi:DOI:10.3969/j.issn.1000-7377.2022.11.003]
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辛伐他汀对创伤性脑损伤小鼠继发性炎症抑制作用及机制研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
51
期数:
2022年11期
页码:
1332-1336
栏目:
基础研究
出版日期:
2022-11-05

文章信息/Info

Title:
Inhibitory effect and mechanism of simvastatin on secondary inflammation in mice with traumatic brain injury
作者:
李张珂1; 马 涛1; 满明昊2; 田 博2
(1.西安国际医学中心医院,陕西 西安 710100; 2.空军军医大学唐都医院,陕西 西安 710038)
Author(s):
LI Zhangke; MA Tao; MAN Minghao; TIAN Bo
(Xi'an International Medical Center Hospital,Xi'an 710100,China)
关键词:
创伤性脑损伤;  辛伐他汀;  炎性反应;  炎症因子;  小胶质细胞;  神经保护
Keywords:
Traumatic brain injury;  Simvastatin;  Inflammatory response;  Inflammatory cytokines;  Microglia;  Neuroprotection
分类号:
R 641
DOI:
DOI:10.3969/j.issn.1000-7377.2022.11.003
文献标志码:
A
摘要:
目的:观察辛伐他汀对创伤性脑损伤小鼠的抗炎和神经保护作用并探讨其机制。方法:选择6～8周龄C57成年雄性小鼠36只,随机均分成损伤组(TBI组)、损伤后应用辛伐他汀组(药物干预组,DI组)和假手术组(Sham组); Feency法进行TBI小鼠模型制作,Sham组仅手术打开骨窗而不进行损伤; DI组小鼠造模成功后腹腔注射辛伐他汀,TBI组和Sham组腹腔注射等体积的0.9%氯化钠溶液,连续给药7 d,1次/d。第1、3、7 天后行脑创伤后mNSS评分,对小鼠进行脑组织含水量测定,Western blot法测定炎症信号通路相关蛋白TBK1、TLR4的表达量,利用ELISA法检测损伤区周围脑组织中炎症因子肿瘤坏死因子-α(TNF-α)和白细胞介素1β(IL-1β)的表达,免疫荧光法检测TBI后脑组织中小胶质细胞的活化情况。结果:相比于Sham组,TBI组和DI组小鼠的mNSS评分显著升高(均P<0.001),与TBI组小鼠相比,DI组小鼠的评分明显降低(均P<0.001); 相较于TBI组,DI组的辛伐他汀治疗可以降低小鼠脑组织中TNF-α、IL-1β的表达水平(均P<0.01); 免疫荧光检测结果显示与Sham组相比,TBI组小鼠损伤区周围组织中出现了大量胞体增大、突起变短的活化状态的小胶质细胞,而较TBI组,DI组中活化状态的小胶质细胞的数量明显减少; 相较于TBI组,DI组中的辛伐他汀治疗可以降低炎症信号通路相关蛋白TBK1、TLR4 的表达水平(均P<0.05)。结论:辛伐他汀对小鼠创伤性脑损伤有一定的治疗作用,能够通过抑制小胶质细胞活化,降低炎症因子和炎症信号通路相关蛋白的表达水平从而抑制创伤性脑损伤后的炎性反应,进一步发挥神经保护的作用。
Abstract:
Objective:To observe the anti-inflammatory and neuroprotective effects of simvastatin on mice with traumatic brain injury and explore its mechanism.Methods:A total of 36 adult male C57 mice aged 6 to 8 weeks were randomly divided into craniocerebral injury group(TBI group),simvastatin administration group(DI group)and Sham group,with 12 mice in each group.Feency method was used to make TBI mouse model.In the Sham group,only bone window was opened without percussion.After molding,mice in the DI group were injected with simvastatin intraperitoneally,and mice in the TBI group and Sham group were injected with equal amount of 0.9% sodium chloride solution every 24 hours for 7 times.Post-traumatic mNSS scores were performed after 1st,3rd and 7th days.The water content of mouse brain tissue was measured.Western blot was used to determine TBK1 and TLR4.The levels of TNF-α and IL-1β in the brain tissue around the injured area were measured by ELISA.Immunofluorescence assay was used to detect the activation of microglia in brain tissue after TBI.Results:Compared with Sham group,the mNSS scores of TBI group and DI group were significantly increased(all P<0.001).Compared with TBI group,the mNSS scores of DI group were significantly decreased(all P<0.001).Compared with TBI group,simvastatin treatment in DI group could reduce the expression levels of TNF-α and IL-1β in brain tissue of mice(all P<0.01).Immunofluorescence detection results showed that compared with the Sham group,a large number of activated microglias with enlarged cell bodies and shortened processes appeared in the tissues around the injury area in the TBI group,while the number of activated microglias in the DI group was significantly reduced compared with the TBI group.Compared with TBI group,simvastatin treatment in the DI group reduced inflammatory signaling pathway associated protein TBK1 and TLR4(all P<0.05).Conclusion:Simvastatin has a certain therapeutic effect on traumatic brain injury in mice.Simvastatin can inhibit the inflammatory response after traumatic brain injury by inhibiting microglia activation and reducing the expression levels of inflammatory factors and inflammatory signaling pathway-related proteins,thus playing a further neuroprotective role.

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更新日期/Last Update: 2022-11-09