摘要
目的:研究β-石竹烯(β-caryophyllene,BCP)对脑缺血再灌注损伤(Cerebral ischemia-reperfusion,CIR)小鼠的保护作用及可能的机制。方法:将C57BL/6小鼠随机分组为假手术组(Sham)、模型组(CIR)、β-石竹烯组(62、124、248mg/kg)。采用线栓法建立小鼠CIR损伤模型,缺血1 h,再灌注24 h后,进行神经行为学评分和脑梗死体积测定;TUNEL法观察CIR后缺血区神经细胞的死亡情况;Western blot法检测脑组织中TLR4和NF-κB(p65)蛋白表达情况;免疫组织化学法检测缺血侧脑NF-κB(p65)的表达;ELISA法检测CIR小鼠血清中HMGB1和缺血侧脑组织中IL-1β、TNF-α的含量变化。结果:与模型组相比,BCP(248 mg/kg)可明显改善小鼠神经功能,减少脑梗死体积,降低缺血区神经元的死亡率(P<0.01);降低血清中HMGB1浓度、TLR4的蛋白表达量(P<0.01),抑制炎症通路NF-κB的激活并减少TNF-α、IL-1β的释放(P<0.01)。结论:BCP能够减轻CIR诱导的小鼠脑组织损伤,其保护作用可能是通过抑制HMGB1/TLR4/NF-κB介导的炎症反应。
Objective： investigate the effect of β-caryophyllene （BCP） on cerebral ischemia-reperfusion （CIR） injury in mice. Methods： Mice were subjected to CIR with or without BCP（62,124,248 mg/kg）. At 24 h of reperfusion,ischemic degrees were determined according to neurologic dysfunction score and cerebral infarct volume. The protein expression of Toll-like receptor（TLR）4 was measured by Western blot. Nuclear factor KB（NF-KB） p65 were measured by immunohistochemistry and Western blot. IL-1 β ,tumor necrosis factor-α（TNF-α）and serum high-mobility group box 1 （HMGB1）levels were measured by ELISA kit. Results： Compared to the CIR group, BCP（248 mg/kg）reduced the neurological score and cerebral infarct volume. BCP reduced neuronal death in mice brain subjected to cerebral I/R. In addition, BCP also inhibited the activation of NF-κB pathway and decreased increases in TLR4, HMGB1, TNF-α, IL-1β levels by CIR（ P〈0. 01 ）. Conclusion： BCP protects mice brain against CIR injury, its neuroprotective mechanisms may involves HMGB1/TLR4/NF-κB pathway.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2017年第7期1009-1013,共5页
Chinese Journal of Immunology
基金
重庆市自然科学基金重点项目(KJ1600235
CSTC2016jcyjA 0258)
关键词
β-石竹烯
缺血再灌注损伤
炎症
TLR4
HMGB1
β-caryophyllene
Ischemia-reperfusion injury
Inflammation
Toll-like receptor 4
High-mobility group box 1
