脑灵汤对阿尔兹海默病模型大鼠NF-κB和IκB表达的影响
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摘要
目的:研究探讨脑灵汤对阿尔兹海默病大鼠模型的保护作用及其对NF-κB和IκB表达的影响。方法:采用脑立体定位仪往海马CA_3区注射Aβ_(1-42)建立阿尔兹海默病大鼠模型,通过行为学和形态学实验观察脑灵汤对模型大鼠的保护作用;通过免疫组化染色观察脑灵汤对模型大鼠NF-κB和IκB表达的影响。结果:脑灵汤组在电刺激Y-迷宫实验成绩考察较模型组优异(P<0.05);脑灵汤组大鼠Morris水迷宫实验过程中搜索所需时间较模型组少(P<0.05);刚果红染色结果示脑灵汤组海马CA_3区未见特征性显示;HE染色结果显示脑灵汤组大鼠海马CA_3区细胞形态、层次结果均较模型组好转;免疫组化染色结果显示模型组大鼠海马CA_3区NF-κB阳性细胞数较正常和假手术组明显增多(P<0.05),而IκB阳性细胞数结果与之相反,较正常和假手术组减少(P<0.05),脑灵汤干预治疗后,大鼠海马CA_3区内NF-κB蛋白表达较模型组变少(P<0.05),IκB的蛋白表达与之相反,较模型组增加(P<0.05)。结论:脑灵汤发挥保护阿尔兹海默病模型大鼠的作用,其可能机制是抑制NF-κB的表达和提高IκB的表达。
Objective:To study the protective effect of Naoling decoction on Alzheimer's disease rat model and its effect on the expression of NF-κB and IκB.Methods:A rat model of Alzheimer's disease was established by injecting Aβ_(1-42) into hippocampal CA_3 area with brain stereotaxic apparatus.The protective effect of Naoling decoction on model rats was observed by behavioral and morphological experiments,and the effect of Naoling decoction on the expression of NF-κB and IκB in model rats was observed by immunohistochemical staining.Results:Naoling decoction group was better than model group in Y-maze test results(P<0.05);Naoling decoction group spent less time searching Morris water maze test than model group(P<0.05);Congo red staining results showed that there was no characteristic expression in CA_3 area of hippocampus in Naoling decoction group;HE staining results showed that the morphology and level of cells in Naoling decoction group rats of CA_3 area were better than those in model group.Immunohistochemical staining showed that the number of NF-κB positive cells in model group of CA_3 area of hippocampus were remarkably more than that in normal and sham-operated group(P<0.05),while the number of IκB positive cells was significantly lower than that in normal and sham-operated group(P<0.05).The number of NF-κB positive cells in CA_3 area of hippocampus in Naoling decoction group was significantly lower than that in model group(P<0.05),while the number of IκB positive cells in Naoling decoction were remarkably more than that in model group(P<0.05).Conclusion:Naoling decoction can protect Alzheimer's disease rats by inhibiting the expression of NF-κB and increasing the expression of IκB.
Objective:To study the protective effect of Naoling decoction on Alzheimer's disease rat model and its effect on the expression of NF-κB and IκB.Methods:A rat model of Alzheimer's disease was established by injecting Aβ_(1-42) into hippocampal CA_3 area with brain stereotaxic apparatus.The protective effect of Naoling decoction on model rats was observed by behavioral and morphological experiments,and the effect of Naoling decoction on the expression of NF-κB and IκB in model rats was observed by immunohistochemical staining.Results:Naoling decoction group was better than model group in Y-maze test results(P<0.05);Naoling decoction group spent less time searching Morris water maze test than model group(P<0.05);Congo red staining results showed that there was no characteristic expression in CA_3 area of hippocampus in Naoling decoction group;HE staining results showed that the morphology and level of cells in Naoling decoction group rats of CA_3 area were better than those in model group.Immunohistochemical staining showed that the number of NF-κB positive cells in model group of CA_3 area of hippocampus were remarkably more than that in normal and sham-operated group(P<0.05),while the number of IκB positive cells was significantly lower than that in normal and sham-operated group(P<0.05).The number of NF-κB positive cells in CA_3 area of hippocampus in Naoling decoction group was significantly lower than that in model group(P<0.05),while the number of IκB positive cells in Naoling decoction were remarkably more than that in model group(P<0.05).Conclusion:Naoling decoction can protect Alzheimer's disease rats by inhibiting the expression of NF-κB and increasing the expression of IκB.
引文
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[3]赵兵兵,李涛,闫咏梅.红景天苷及其苷元酪醇抗炎作用研究进展[J].转化医学电子杂志,2018,5(8):55-58.
[4]杨春,章茜,韦迎娜,等.β-淀粉样蛋白致大鼠Alzheimer病模型的研究[J].河南医学研究,2003,12(4):294-296.
[5] Ahmad MH,Fatima M,Mondal AC.Influence of microglia and astrocyte activation in the neuroinflammatory pathogenesis of Alzheimer’s disease:Rational insights for the therapeutic approaches[J].J Clin Neurosci,2018,10:29.
[6] Latta C,Brothers H,Wilcock D.Neuroinflammation in Alzheimer’s disease:a source of heterogeneity and target for personalized therapy[J].Neuroscience,2014,302:103-111.
[7] Eikelenboom P,Van Exel E,Veerhuis R,et al.Innate immunity and the etiology of late-onset Alzheimer’s disease[J].Neurodegener Dis,2012,10:271-273.
[8] Peng DT,Yuan XR,Zhu R.Memantinehydrochloride in the treatment of dementia subtypes[J].J Clin Neurosci,2013,20:1482-1485.
[9]胡起超,于涛,韩景献.老年性痴呆中医症候及病因病机探析[J].陕西中医,2010,31(5):576-577.
[10]省格丽.益智治呆方加减治疗脾肾两虚型老年性痴呆的临床疗效研究[J].陕西中医,2016,37(8):966-967.
[11]张利平,彭静.清心益智汤对于改善阿尔茨海默病患者生活质量、认知水平以及SOD、MDA等生化指标的作用分析[J].陕西中医,2018,39(5):593-595.
[12] Guo J,Li F,Wu Q,et al.Protective effects of icariin in brain dysfunction induced by lipopolysaccharide in rats[J].Phytomedicine,2010,17(12):950-955.
[13]陈洋,平键,张晶,等.淫羊藿苷提高SIRT6酶活性及抑制小鼠NF-кB炎症信号通路的实验研究[J].老年医学与保健,2012,18(6):338-346.
[14] Li D,Fu Y,Zhang W,et al.Salidroside attenuates inflammatory responses by suppressing nuclear factor-κB and mitogen activated protein kinases activation in lipopolysaccharide-induced mastitis in mice[J].Inflamm Res,2013,62(1):9-15.
[15]郑明昱,金哲悟,朴红梅,等.红景天苷通过NF-κB/TGF-β1信号通路抑制哮喘小鼠气道重塑的实验研究[J].中草药,2014,17(9):2511-2516.
[16]楚晋,叶翠飞.二苯乙烯苷对β-淀粉样肽致痴呆小鼠模型行为学及胆碱能功能的影响[J].基础医学与临床,2006,26(2):197-198.