金钗石斛多糖上调锌指蛋白A20表达减轻大鼠缺血性脑损伤

目的观察金钗石斛多糖调控锌指蛋白A20表达抑制NF-κB信号通路减轻大鼠缺血-再灌注脑损伤的作用机制。方法 SD大鼠随机分为假手术组、脑缺血-再灌注模型组、金钗石斛多糖治疗组(200 mg/kg)、金钗石斛多糖治疗+A20沉默组和金钗石斛多糖治疗+空病毒载体组。建立局灶性脑缺血-再灌注模型,观察金钗石斛多糖对锌指蛋白A20 mRNA和蛋白表达的影响。比较各组大鼠神经功能评分和脑梗死体积,检测磷酸化IKKβ蛋白和胞核p65蛋白的表达量。结果分别从再灌注6 h和12 h开始,金钗石斛多糖治疗组大鼠脑组织A20 mRNA和蛋白水平均较脑缺血-再灌注模型组明显增高(均P0.01)。同脑缺血-再灌注模型组相比,金钗石斛多糖治疗组大鼠神经功能评分明显改善(P0.001),脑梗死体积明显减小(P0.01),脑组织磷酸化IKKβ和胞浆p65表达水平均明显下降(分别为P0.001,P0.01);而A20沉默则逆转了金钗石斛多糖上述治疗效果,各项指标均明显恶化(均P0.01)。结论金钗石斛多糖通过上调锌指蛋白A20表达抑制NF-κB信号通路减轻大鼠缺血性脑损伤。

Dendrobium nobile polysaccharides mitigate SD rats cerebral ischemia injury by upregulating zinc finger protein A20

Objective To observe the effects of Dendrobium nobile polysaccharides regulating A20 to mitigate rat cerebral ischemia-reperfusion injury.Methods SD male rats were randomly allocated into Sham group,MCAO group,MCAO+DNP therapy (DT,200 mg/kg) group,MCAO+DT+LV-shA20 group,MCAO+DT+Vehicle group.By establishing MCAO rat model,the effects of DNP on A20 mRNA and protein expression were detected by RT-qPCR and Western blot.At same time rats neurological deficit score and infarct volume were compared in groups,and their phosphorylated IKKβ (p-IKKβ) protein and nuclear p65 protein levels were further investigated by Western blot.Results Compared with MCAO group,A20 mRNA and protein levels significantly elevated in MCAO+DT group at each time point (each time point P<0.01) beginning from reperfusion 6 h and 12 h respectively in MCAO+DT group.Compared with MCAO group,MCAO+DT group rats shown significant improved neurological deficit score,smaller infarct volume,and decreased brain tissue p-IKKβ and nuclear p65 protein (P<0.001,P<0.01,P<0.001,P<0.01,respectively);however,A20 silencing significant worsen all the above index (each P<0.01),as compared with MCAO+DT group.Conclusion DNP inhibit NF-κB signaling and attenuate SD rats cerebral ischemia injury by upregulating zinc finger protein A20.