β-石竹烯通过抗氧化作用减轻局灶性脑缺血再灌注大鼠大脑皮质损伤

β-caryophyllene protects cerebral cortical neurons against cerebral ischemia and reperfusion in rats by improving antioxidant activities

目的:探讨β-石竹烯(β-Caryophyllene)对脑缺血再灌注大鼠的保护作用及其机制。方法:将75只SD大鼠随机分为5组:假手术组(Sham);模型组(I/R);β-石竹烯34mg/kg组;β-石竹烯102mg/kg组;β-石竹烯306mg/kg组。采用线栓法建立大鼠大脑中动脉栓塞(Middle Cerebral Artery Occlusion,MCAO)模型,缺血1.5h,再灌注24h后,采用双盲法进行神经行为学评分;尼氏染色法(Nissl)测定大脑皮质神经元缺损情况;原位末端凋亡法(TUNEL)检测皮质神经元凋亡情况;测定皮质中超氧化物歧化酶(SOD)、丙二醛(MDA)含量;Western法检测核因子相关因子2(NF-E2-related factor,Nrf2)及血红素氧合酶1(heme oxygenase 1,HO-1)表达。结果:β-石竹烯102mg/kg、306mg/kg剂量范围内可显著改善MCAO大鼠神经缺损功能;减轻皮质神经元缺损及细胞凋亡情况;上调SOD水平,降低MDA含量;上调Nrf2、HO-1蛋白的表达。结论:β-石竹烯对脑缺血再灌注大鼠具有保护作用,此作用可能与其抗氧化作用有关。

Objective： To investigate protective effect and mechanism of β-Caryophyllene on ischemic stroke in rats. Methods： Totally 75 SpragueDawley（ SD） rats were randomly divided into five groups： Sham group,ischemia-reperfusion group（ IR）,β-Caryophyllene 34 mg / kg group,β-Caryophyllene 102 mg /kg group,β-Caryophyllene 306 mg /kg group. Reforming Longa method was used to establish focal cerebral ischemia and reperfusion model. Focal cerebral ischemia was induced by 90 mins of Middle Cerebral Artery Occlusion（ MCAO） followed by 24 h of reperfusion. After that,the neurological deficit score were evaluated by Longa＇s score,cortical neuronal loss was observed by Nissl staining.Cortical neuronal apoptosis cells were detected by TUNEL staining. Superoxide dismutase（ SOD） activity and malondialdehyde（ MDA） levels in brain cortex were detected. The expression levels of nuclear factor erythroid 2-related factor 2（ Nrf2） and heme oxygenase-1（ HO-1）were analysed by Western blotting. Results： In the dose range of 102 ~ 306 mg / kg,β-Caryophyllene can improve the nerve function impairment,alleviate the cortical neurons loss and apoptosis,renovated the SOD activity,decrease the level of MDA,upregulated the protein expressions of Nrf2 and HO-1. Conclusion： β-Caryophyllene has the obvious protective effect on the brain ischemia-reperfusion injury in rats.Its mechanism may be related to its antioxidant activities.