石杉碱甲对急性炎症小鼠室旁核和脑干c-Fos和GFAP表达的影响
|
摘要
目的:探讨石杉碱甲对急性炎症小鼠下丘脑室旁核和脑干神经元c-Fos和星形胶质细胞(astrocytes,AST)胶质原纤维酸性蛋白(glial fiberillany acidic protein,GFAP)表达的影响.方法:①采用蛋清致小鼠足趾肿胀模型,检测致炎后30min,1h,2h的小鼠足容积并计算肿胀度;②免疫组化技术检测孤束核、迷走背核及室旁核神经元c-Fos及星形胶质细胞GFAP的表达.结果:①与生理盐水组比较,不同浓度的石杉碱甲均可明显抑制蛋清致小鼠足肿胀(P<0.05或P<0.01).②与对照组相比,致炎组小鼠孤束核和室旁核内Fos免疫阳性神经元(Fos-immunoreactive neurons,Fos-IR)及GFAP免疫阳性星形胶质细胞(GFAP-immunoreactive astrocytes,GFAP-IR)数目均明显增多(P<0.01),而迷走背核增加不显著(P>0.05).与致炎组相比,石杉碱甲给药组孤束核、迷走背核及室旁核内Fos-IR神经元及GFAP-IR星形胶质细胞数目均明显增多(P<0.01).结论:石杉碱甲对蛋清致小鼠足肿胀有明显的抗炎作用;石杉碱甲能够显著增强急性炎症小鼠孤束核、迷走背核及室旁核内神经元和星形胶质细胞的活动.
Obejective:To investigate the effect of huperzine A on c-Fos and GFAP expression in the paraventricular nucleus and the brainstem of mice with acute inflammation.Methods:Animal models of paw edema induced by egg white were set up,then the volume of swelling foot and the degree of swelling were measured at 30min,1hand 2hafter egg white–induced acute inflammation.Additionally,immunohistochemistry staining technique was used to determine the expression of c-Fos and GFAP in the nucleus of solitary tract,the dorsal motor nucleus of the vagus and the paraventricular nucleus of hypothalamus.Results:Compared with the control group,huperzine A with different concentrations could significantly restrain paw edema induced by egg white(P<0.05or P<0.01).In the inflammatory group,the number of Fos-IR neurons and GFAP-IR astrocytes in the NTS and PVN were significantly increased(P<0.01),but not in the DMV.Besides,compared to those in the inflammatory group,Fos-IR neurons and GFAP-IR astrocytes in the NTS,DMV and PVN of mice pretreated with huperzine A were significantly increased(P<0.01).Conclusion:Huperzine A has a significant anti-inflammatory effect on paw edema induced by egg white.Moreover,huperzine A could improve the activities of neurons and astrocytes in NTS,DMV and PVN during actue inflammation.
Obejective:To investigate the effect of huperzine A on c-Fos and GFAP expression in the paraventricular nucleus and the brainstem of mice with acute inflammation.Methods:Animal models of paw edema induced by egg white were set up,then the volume of swelling foot and the degree of swelling were measured at 30min,1hand 2hafter egg white–induced acute inflammation.Additionally,immunohistochemistry staining technique was used to determine the expression of c-Fos and GFAP in the nucleus of solitary tract,the dorsal motor nucleus of the vagus and the paraventricular nucleus of hypothalamus.Results:Compared with the control group,huperzine A with different concentrations could significantly restrain paw edema induced by egg white(P<0.05or P<0.01).In the inflammatory group,the number of Fos-IR neurons and GFAP-IR astrocytes in the NTS and PVN were significantly increased(P<0.01),but not in the DMV.Besides,compared to those in the inflammatory group,Fos-IR neurons and GFAP-IR astrocytes in the NTS,DMV and PVN of mice pretreated with huperzine A were significantly increased(P<0.01).Conclusion:Huperzine A has a significant anti-inflammatory effect on paw edema induced by egg white.Moreover,huperzine A could improve the activities of neurons and astrocytes in NTS,DMV and PVN during actue inflammation.
引文
[1]章海燕,唐希灿.石杉碱甲:具有治疗神经退行性疾病的前景药物[J].上海医药,2003,24(3):112-120.
[2]Wang Z F,Wang J,Zhang H Y,et al.Huperzine A exhibits anti-inflammatory and neuroprotective effects in a rat model of transient focal cerebral ischemia[J].J Neurochem,2008,106(4):1594-1603.
[3]Pavlov V A,Parrish W R,Rosas-Ballina M,et al.Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway[J].Brain Behav Immun,2009,23(1):41-45.
[4]Pavlov V A,Oehani M,Gallowitsch-Puerta M,et al.Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia[J].PNAS,2006,103(13):5219–5223.
[5]程世斌,卢光启.迷走神经背核的研究进展[J].生理科学进展,1996,27(1):13-18.
[6]张锐武,唐希灿,韩燕艺,等.石杉碱甲治疗老年期记忆障碍的药物评价[J].中国药理学报,1991,12(3):250-252.
[7]Nizri E,Hamra-Amitay Y,Sicsic C,et al.Anti-inflammatory properties of cholinergic up-regulation:A new role for acetylcholinesterase inhibitors[J].Neuropharmacology,2006,50(5):540-547.
[8]Pavlov V A,Tracey K J.The cholinergic anti-inflammatory pathway[J].Brain Behav Immun,2005,19(6):493-439.
[9]Belevych N,Buchanan K,Chen Q,et al.Location-specific activation of the paraventricular nucleus of the hypothalamus by localized inflammation[J].Brain Behav Immun,2010,24(7):1137-1147.
[10]FO The,C Cailotto,J van der Vliet,et al.Central activation of the cholinergic anti-inflammatory pathway reduces surgical inflammation in experimental post-operative ileus[J].Br J Pharmacol,2011,163(5):1007-1016.
[11]张磊,万谦宏,高文远.石杉碱甲的研究进展[J].中草药,2005,36(9):1422-1426.
[12]Song H J,Stevens C F,Gage F H.Astroglia induce neurogenesis from adult neural stem cells[J].Nature,2002,417:39-43.
[13]段丽,田国红,饶志仁.大鼠脑内星形胶质细胞对渗透压改变的反应及其和神经元的相互关系[J].神经解剖学杂志,2001,17(2):175-178.
[14]Fields R D,Stevens-Graham B.New Insights into Neuron-Glia Communication[J].Science,2002,298(5593):556-562.
[15]Stipursky J,RomL,Tortelli V,Neto VM,et al.Neuron-glia signaling:Implications for astrocyte differentiation and synapse formation[J].Life Sci,2011,89(15/16):524-553.
[2]Wang Z F,Wang J,Zhang H Y,et al.Huperzine A exhibits anti-inflammatory and neuroprotective effects in a rat model of transient focal cerebral ischemia[J].J Neurochem,2008,106(4):1594-1603.
[3]Pavlov V A,Parrish W R,Rosas-Ballina M,et al.Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway[J].Brain Behav Immun,2009,23(1):41-45.
[4]Pavlov V A,Oehani M,Gallowitsch-Puerta M,et al.Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia[J].PNAS,2006,103(13):5219–5223.
[5]程世斌,卢光启.迷走神经背核的研究进展[J].生理科学进展,1996,27(1):13-18.
[6]张锐武,唐希灿,韩燕艺,等.石杉碱甲治疗老年期记忆障碍的药物评价[J].中国药理学报,1991,12(3):250-252.
[7]Nizri E,Hamra-Amitay Y,Sicsic C,et al.Anti-inflammatory properties of cholinergic up-regulation:A new role for acetylcholinesterase inhibitors[J].Neuropharmacology,2006,50(5):540-547.
[8]Pavlov V A,Tracey K J.The cholinergic anti-inflammatory pathway[J].Brain Behav Immun,2005,19(6):493-439.
[9]Belevych N,Buchanan K,Chen Q,et al.Location-specific activation of the paraventricular nucleus of the hypothalamus by localized inflammation[J].Brain Behav Immun,2010,24(7):1137-1147.
[10]FO The,C Cailotto,J van der Vliet,et al.Central activation of the cholinergic anti-inflammatory pathway reduces surgical inflammation in experimental post-operative ileus[J].Br J Pharmacol,2011,163(5):1007-1016.
[11]张磊,万谦宏,高文远.石杉碱甲的研究进展[J].中草药,2005,36(9):1422-1426.
[12]Song H J,Stevens C F,Gage F H.Astroglia induce neurogenesis from adult neural stem cells[J].Nature,2002,417:39-43.
[13]段丽,田国红,饶志仁.大鼠脑内星形胶质细胞对渗透压改变的反应及其和神经元的相互关系[J].神经解剖学杂志,2001,17(2):175-178.
[14]Fields R D,Stevens-Graham B.New Insights into Neuron-Glia Communication[J].Science,2002,298(5593):556-562.
[15]Stipursky J,RomL,Tortelli V,Neto VM,et al.Neuron-glia signaling:Implications for astrocyte differentiation and synapse formation[J].Life Sci,2011,89(15/16):524-553.