摘要
目的:观察阿魏酸钠对大鼠脑缺血再灌注炎症损伤的保护作用,并探讨其作用机制。方法:取SD雄性大鼠,建立大脑中动脉阻塞(MCAO)致脑缺血/再灌注损伤模型,造模成功的36只随机分成模型组,阿魏酸钠低、中、高剂量组(25,50,100 mg·kg^-1),并另取9只作为假手术组。采用神经功能评分法观察大鼠神经功能情况;苏木精-伊红(HE)染色观察大鼠脑组织病理学形态变化;酶联免疫吸附测定(ELISA)检测大鼠血清和脑组织中肿瘤坏死因子-α(TNF-α),白细胞介素-1β(IL-1β),白细胞介素-6(IL-6)含量变化;蛋白免疫印迹法(Western blot)检测缺血周边区核转录因子-кB p65 (NF-κB p65)蛋白表达。结果:与假手术组比较,模型组大鼠神经行为学评分升高,神经元坏死,大量炎症细胞产生,血清和脑组织中TNF-a,IL-1β,IL-6水平显著升高(P<0. 01),细胞核/细胞浆NF-κB p65蛋白表达比例显著升高(P<0. 01);与模型组比较,阿魏酸钠可明显降低脑损伤大鼠神经行为学评分(P<0. 05,P<0. 01),抑制神经元坏死,减少炎症细胞产生,并可明显降低血清和脑组织中TNF-a,IL-1β,IL-6水平(P<0. 05,P<0. 01),抑制NF-κB p65由细胞质向细胞核转位(P<0. 05,P<0. 01),最终减轻缺血再灌注造成的神经细胞炎症损伤。结论:阿魏酸钠可通过抑制NF-κB p65核转位减轻缺血再灌注大鼠脑神经细胞炎症反应,维持脑部正常形态,这可能是其发挥脑保护作用的机制之一。
Objective: To investigate the protective effect of sodium ferulate on cerebral ischemiareperfusion injury in rats and to explore its possible mechanism. Method: The cerebral ischemia reperfusion injury model was established by middle cerebral artery occlusion( MCAO) in SD male rats. 36 modeled rats with neurologic damage were randomly divided into 4 groups: model group,low,medium,high-dose sodium ferulate groups( 25,50,100 mg·kg^-1). Another nine rats were selected as a sham operation group. Neurological function was assessed by neurological scoring system in rats. Hematoxylin-eosin( HE) staining was performed to observe the pathological changes of the rats' brain. The levels of tumor necrosis factor α( TNF-α),interleukin-1β( IL-1β) and interleukin-6( IL-6) in serum and brain tissues were detected by enzyme-linked immunosorbent assay( ELISA). Western blot was used to detect the protein expression of nucleus and cytoplasm nuclear factor-kappa B p65( NF-κB p65) in brain tissues. Result: As compared with normal group,neurological deficit score was increased;the neuronal necrosis and inflammatory cell number were present;the serum and brain tissue levels of TNF-α,IL-1β and IL-6 were increased;nucleus/cytoplasm NF-κB p65 protein expression ratio was increased significantly in model group( P< 0. 01). As compared with model group,sodium ferulate distinctly decreased the neurological deficit score( P< 0. 05,P< 0. 01),inhibited neuronal necrosis,reduce inflammatory cell number,significantly reduce the serum and brain tissue levels of TNF-α,IL-1β and IL-6( P< 0. 05,P< 0. 01). Western blot showed that sodium ferulate could inhibit the nuclear translocation of NF-κB p65 protein( P< 0. 05,P<0. 01),and finally,it can alleviate the inflammatory injury caused by ischemia reperfusion. Conclusion: Sodium ferulate protects the brain against focal cerebral ischemia reperfusion injury,and the mechanism may be related to inhibiting nuclear translocation of NF-κB p65 protein to alleviate inflammatory response.
作者
龚婉
陈晓玲
周莉
章科娜
GONG Wan;CHEN Xiao-ling;ZHOU Li;ZHANG Ke-na(College of Basic Medical Science,Zhejiang Chinese Medical University,Hangzhou 310053,China;.The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 510006,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2019年第3期94-99,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
浙江中医药大学校级科研基金项目(2014ZY01)
浙江中医药大学基础医学院科研基金项目(JC201409)
