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、248 mg/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 κB(NF-κB)p65 were measured by immunohistochemistry and Western blot.IL-1β,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.
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