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姜黄素通过抑制外伤性癫痫鼠脑组织中mTORC1的表达发挥抗癫痫效应

, PP. 414-419

Keywords: 姜黄素,哺乳动物雷帕霉素靶蛋白复合物,外伤性癫痫,三氯化铁

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Abstract:

目的探讨姜黄素在外伤性癫痫鼠中的抗癫痫效应及对哺乳动物雷帕霉素靶蛋白复合物1(mammaliantargetofrapamycin,mTORcomplex1,mTORC1))表达的影响。方法120只SD雄性大鼠按抽签法随机分为对照组、模型组和干预组,每组40只。模型组与干预组构建大鼠皮质铁离子注射癫痫模型,对照组予以生理盐水注射,干预组于造模前1h腹腔注射姜黄素,连续14d。各实验组于造模后6、24h、3、7、14d时间点进行相应实验。观察大鼠癫痫发作情况,记录大鼠皮层脑电图特点,透射电镜观察注射侧皮层神经元,Westernblot检测大鼠注射侧皮层mTORC1蛋白的表达及其磷酸化程度(p-mTORC1),免疫组化法检测p-mTORC1蛋白在大鼠注射侧皮层中的表达。结果对照组未见癫痫发作,干预组较模型组癫痫发作次数明显减少(P<0.05),发作程度明显减轻(P<0.05);脑电图提示干预组脑电波波幅及癫痫波次数较模型组明显减低(P<0.05);电镜见模型组大鼠神经元变性、死亡等改变,干预组大鼠神经元亚细胞结构基本正常;Westernblot检测结果显示mTORC1蛋白在模型组中各时间点磷酸化激活程度均显著高于对照组(P<0.05),并于术后24h达到峰值,在干预组中p-mTORC1显著低于模型组(P<0.05);免疫组化结果提示p-mTORC1在对照组中低表达,模型组中显著高于对照组(P<0.05),干预组中p-mTORC1显著低于模型组(P<0.05)。结论在外伤性癫痫大鼠中,姜黄素可能通过抑制mTORC1磷酸化激活而发挥抗癫痫效应。

References

[1]  Russo E, Citraro R, Constanti A,et al. The mTOR signaling pathway in the brain: focus on epilepsy and epileptogenesis[J]. Mol Neurobiol, 2012, 46(3): 662-681.? [2]Ryther R C, Wong M. Mammalian target of rapamycin (mTOR) inhibition: potential for antiseizure, antiepileptogenic, and epileptostatic therapy[J]. Curr Neurol Neurosci Rep, 2012, 12(4): 410-418.? [3]Guo D, Zeng L, Brody D L,et al. Rapamycin attenuates the development of posttraumatic epilepsy in a mouse model of traumatic brain injury[J]. PLoS One, 2013, 8(5): e64078. [4]Jyoti A, Sethi P, Sharma D. Curcumin protects against electrobehavioral progression of seizures in the iron-induced experimental model of epileptogenesis[J]. Epilepsy Behav, 2009, 14(2): 300-308.? [5]Choudhary K M, Mishra A, Poroikov V V,et al. Ameliorative effect of Curcumin on seizure severity, depression like behavior, learning and memory deficit in post-pentylenetetrazole-kindled mice[J]. Eur J Pharmacol, 2013, 704(1/3): 33-40.? [6]肖淳, 王文, 石全红, 等. STIM1在幼年和成年大鼠外伤性癫痫中的表达[J]. 第三军医大学学报, 2013, 35(14): 1493-1497.? [7]D’Ambrosio R, Fairbanks J P, Fender J S,et al. Post-traumatic epilepsy following fluid percussion injury in the rat[J]. Brain, 2004, 127(Pt 2): 304-314.? [8]陈敏若, 石全红, 谢延风, 等. 表皮生长因子对铁离子致痫大鼠脑的保护作用[J].第三军医大学学报, 2012, 34(14): 1202-1205.? [9]Pitkanen A, McIntosh T K. Animal models of post-traumatic epilepsy [J]. J Neumtrauma, 2006, 23(2): 241-261. [10]Galanopoulou A S, Gorter J A, Cepeda C. Finding a better drug for epilepsy: the mTOR pathway as an antiepileptogenic target[J]. Epilepsia, 2012, 53(7): 1119-1130.? [11]Huang X, Zhang H, Yang J,et al. Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy[J]. Neurobiol Dis, 2010, 40(1): 193-199.? [12]Wiegand G, May T W, Ostertag P,et al. Everolimus in tuberous sclerosis patients with intractable epilepsy: a treatment option?[J]. Eur J Paediatr Neurol, 2013, 17(6): 631-638.? [13]Sharma R A, Euden S A, Platton S L,et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance[J]. Clin Cancer Res, 2004, 10(20): 6847-6854.? [14]Rafiee P, Binion D G, Wellner M,et al. Modulatory effect of curcumin on survival of irradiated human intestinal microvascular endothelial cells: role of Akt/mTOR and NF-κB[J]. Am J Physiol Gastrointest Liver Physiol, 2010, 298(6): G865-G877.

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