槲皮素对脑梗死大鼠神经细胞凋亡及神经功能的影响

Effects of quercetin on neuronsapoptosis and nerve function in rats with cerebral infarction

目的探究槲皮素对脑梗死大鼠神经细胞凋亡及神经功能的影响。方法构建脑梗死大鼠模型,随机分为模型组及槲皮素低、中、高剂量组(25、50、100 mg/kg槲皮素);另取12只未造模大鼠为假手术组。比较各组大鼠神经功能和脑组织病理情况,末端标记法检测神经细胞凋亡,酶联免疫吸附法检测脑组织炎症因子和生长因子水平,蛋白质印迹法检测凋亡相关蛋白和Toll样受体/核因子-κB(TLR4/NF-κB)通路表达。结果与假手术组比较,模型组神经功能缺损评分、脑梗死体积、神经细胞凋亡率、Caspase-3、Caspase-9、脑源性神经生长因子(BDNF)、血管内皮生长因子(VEGF)、白细胞介素-6(IL-6)、IL-1β、肿瘤坏死因子-α(TNF-α)、TLR4及p-NF-κB/NF-κB水平升高,肝细胞生长因子(HGF)水平降低(P<0.05)。与模型组比较,槲皮素中、高剂量组神经功能缺损评分、脑梗死体积、神经细胞凋亡率、Caspase-3、Caspase-9、IL-6、IL-1β、TNF-α、TLR4及p-NF-κB/NF-κB水平降低,BDNF、VEGF及HGF水平升高(P<0.05)。结论槲皮素可有效保护脑梗死大鼠,主要通过抑制神经细胞凋亡、减轻神经功能损伤、阻滞TLR4/NF-κB通路降低炎症反应。

Aim To explore the effects of quercetin on neurons apoptosis and nerve function in rats with cerebral infarction.Methods The models of cerebral infarction rats were constructed.And then they were randomly divided into model group,low-dose,medium-dose and high-dose quercetin groups(25,50,100 mg/kg quercetin).A total of 12 non-molding rats were enrolled as sham operation group.The nerve function and pathological conditions of brain tissues in different groups were compared.The neuron apoptosis was detected by terminal-deoxynucleoitidyl transferase/(TdT-)mediated nick end labeling(TUNEL).The levels of inflammatory factors and growth factors in brain tissues were detected by enzyme linked immunosorbent assay(ELISA).The expressions of apoptosis-related proteins and Toll-like receptor/nuclear factorκB(TLR4/NF-κB)pathways were detected by Western blot.Results Compared with sham operation group,score of neurological deficits,cerebral infarction volume,neurons apoptosis rate,levels of cysteine aspartase-3(Caspase-3),Caspase-9,brain-derived neurotrophic factor(BDNF),vascular endothelial growth factor(VEGF),interleukin-6(IL-6),IL-1β,tumor necrosis factor-α(TNF-α),TLR4 and p-NF-κB/NF-κB were increased in model group,while level of hepatocyte growth factor(HGF)was decreased(P<0.05).Compared with model group,score of neurological deficits,cerebral infarction volume,neurons apoptosis rate,levels of Caspase-3,Caspase-9,IL-6,IL-1β,TNF-α,TLR4 and p-NF-κB/NF-κB were decreased in medium-dose and high-dose quercetin groups,while levels of BDNF,VEGF and HGF were increased(P<0.05).Conclusion Quercetin can effectively protect rats with cerebral infarction,which can reduce inflammation response by inhibiting neuron apoptosis,alleviating neurological deficits and blocking TLR4/NF-κB pathways.