期刊文献+

KA癫痫大鼠ALK5对TGF-β1-ALK1-p-Smad1通路的影响

The effect of the ALK5 to TGF-β1-ALK1-p-Smad1 pathway in hippocampus of rats with epilepsy induced by kainic acid
下载PDF
导出
摘要 目的研究癫痫大鼠ALK5对ALK1受体的作用,探讨可能的干预癫痫发作的新靶点。方法红藻氨酸(kainic acid,KA)侧脑室注入SD大鼠制备癫痫模型,随机分为KA模型对照组(A组)、ALK5抑制剂(SB431542)腹腔注射3 d组(B组)、ALK5抑制剂腹腔注射7 d组(C组),另设假手术组为空白对照组(NC组),每组各10只。NC组、A组、B组分别于3 d,C组于7 d取海马,检测海马组织中ALK1和其下游分子p-Smad1的mRNA及其蛋白的表达。结果与正常对照组相比,KA模型对照组大鼠海马区ALK1和p-Smad1的mRNA及蛋白表达均升高,差异有统计学意义(P<0.05);与KA模型组相对比,ALK5抑制剂腹腔注射组(B组和C组)ALK1和pSmad1的mRNA及蛋白表达均下降(P<0.05)。结论 ALK5抑制剂腹腔注射后导致KA诱导的SD癫痫大鼠ALK1受体和p-Smad1表达下调。 Abstract: Objective To observe the expression of the mRNA and the protein level of the ALK1 receptor and it' s downstream molecules p-Smadl and study the function of ALK5 receptor to ALK1 receptor after injection of ALK5 inhibitor (SB431542) , in order to explore new targets for possible intervention of epileptic seizures. Methods Male Sprague-Dawley rats were taken for the epileptic model kindled by Kainie acid (KA) and were divided into three groups randomly as KA control group(A) ,ALK5 inhibitor 3 clays group (B) ,ALK5 inhibitor 7 days group (C). Besides, take sham rats for the normal control group. The normal control group and KA group were injected with saline in abdominal cavity for three clays ;The ALK5 inhibitor 3 clays group rats intraperitoneally infused with ALK5 inhibitor for three days ,and the ALK5 inhibitor 7 clays group rats for seven days. The expression of the mRNA and the protein of the ALK1 receptor and p-Smadl in the rats hippoeampus neurons were examined by RT-PCR and immunofluorescenee histochemistry. Results The expression of he ALK1 receptor and p-Smadl in KA group increased ( P 〈 0.05 ) compared with normal control group in the real time quantitative PCR and immunohistoehemistry analysis,in which ALK5 inhibitor 3 days group and ALK5 inhibitor 7 clays group dereased ( P 〈 0. 05 ) compared with KA group. Conclusion After ALK5 inhibitor was injected into the abdominal cavity,the expression of ALK1 receptor and p-Smad1 decreased.
出处 《中风与神经疾病杂志》 CAS CSCD 北大核心 2014年第11期977-981,共5页 Journal of Apoplexy and Nervous Diseases
基金 国家自然科学基金项目(No.81160167)
关键词 癫痫 TGF-Β1 ALK1 P-Smad1 ALK5抑制剂 Epilepsy TGF-β1 ALK1 P-Smadl ALK5 Inhibitor
  • 相关文献

参考文献20

  • 1Brionne TC,Tesseur I, Masliah E, et al. Loss of TGF-beta 1 leads to increased neuronal cell death and microgliosis in mouse brain [ J ]. Neuron ,2003,40 (6) : 1133 - 1145.
  • 2Fabene PF, Merigo F, Galie M, et al. Pilocarpine-induced status epi- lepticus in rats involves ischemic and excitotoxic mechanisms [ J ]. PloS One,2007,2(10) :el 105.
  • 3李良勇,王玉.转化生长因子β1与癫痫[J].中国药理学通报,2012,28(5):597-600. 被引量:2
  • 4王岩,张晾,潘杰.转化生长因子β1在脑积水发生中的作用[J].现代生物医学进展,2009,9(19):3774-3775. 被引量:4
  • 5Konig HG, Kogel D, Rami A, et al. TGF-betal activates two distinct type I receptors in neurons:implications for neuronal NF-kB signaling [J]. J Cell Biol,2005,168(7) :1077 -1086.
  • 6Friedman A, Kaufer D, Heinemann U. Blood-brain barrier breakdown- inducing astrocytic transformation : novel targets for the prevention of epilepsy [ J ]. Epilepsy Res,2009,85 (2 - 3 ) : 142 - 149.
  • 7Lu Y, Xue T, Yuan J, et al. Increased expression of TGF beta type I receptor in brain tissues of patients with temporal lobe epilepsy [ J :. Clin Sci(Lond) ,2009,117 ( 1 ) : 17 - 22.
  • 8Goumans MJ,Valdimarsdottir G,Itoh S,et al. Activin receptor-like ki- nase (ALK) 1 is an antagonistic mediator of lateral TGFbeta/ALK.5 signaling[ J]. Mol Cesll,2003,12 (4) :817 - 828.
  • 9PaxinosG,WatsonC,诸葛启钏.大鼠脑立体定向图谱[M].第3版.人民卫生出版社,2005.1-78.
  • 10Racine ILl. Modification of seizure activity by electrical stimulation. II. Motor seizure[ Jl. Electroencephalogr Clin Neurophysiol, 1972, 32(3) :281 -294.

二级参考文献103

  • 1臧颖卓,范亚林,李虹,王维平.癫痫发病机制的研究现状[J].脑与神经疾病杂志,2009,17(1):78-81. 被引量:25
  • 2刘浩,魏伟.TGFβ信号转导通路及以其为靶点的肝纤维化治疗[J].中国药理学通报,2007,23(5):561-565. 被引量:38
  • 3刘曾旭,王向东,王航辉,刘德明,马建敏.尼莫地平对烫伤大鼠脑内ZO-1 mRNA及血脑屏障通透性的影响[J].中国组织工程研究与临床康复,2007,11(21):4147-4150. 被引量:4
  • 4Jennings MT,Pietenpol JA.The role of transforming growth factor β in glioma progression[J].J Neurooncol,1998,36(2):123-140.
  • 5Verrecchia F,Mauviel A.Transforming growth factor-beta signaling through the Smad pathway:role in extracellular matrix gene expression and regulation[J].J Invest Dermatol,2002,118(2):211-215.
  • 6Oft M,Heider KH,Beug H.TGF2βsignaling is necessary forcarcinoma cell invasiveness and metastasis[J].Curr Biol,1998,8(23):1243-1252.
  • 7Shi Y,Massague J.Mechanisms of TGF-β signaling from cell membrane to the nucleus[J].Cell,2003,113(6):685-700.
  • 8Piek E,Heldin CH,Ten Dijke P.Specificity,diversity,and regulation in TGF-β superfamily signaling[J].FASEB J,1999,13(15):2105-2124.
  • 9Attisano L,Wrana JL.Signal transduction by TGF-β superfamily[J].Science,2002,296(5573):1646-1647.
  • 10Derynck R,Zhang YE.Smad-dependent and Smad-independent pathways in TGF-β family signaling[J].Nature,2003,425(6958):577-584.

共引文献19

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部