中国全科医学Issue(19)：2310-2316,7.DOI:10.3969/j.issn.1007-9572.2015.19.016
重组人红细胞生成素对癫痫持续状态大鼠海马线粒体凋亡途径相关调控因子的影响及作用机制
Effects of rHuEPO on the Regulatory Factors Related With the Apoptosis Pathway of Hippocampal Mitochondria in Rats With Status Epilepticus and the Possible Mechanism
摘要
Abstract
Objective To observe the effect of recombinant human erythropoietin( rHuEPO)on the expression levels of p-PKB/p-Akt,Bax and XIAP in hippocampal neurons of male mature SD rats with pentylenetetrazol( PTZ)induced status epilepticus( SE),and to further investigate the possible mechanism. Methods The included male mature rats of clean grade were provided by Laboratory Animal Center of Hebei Province in March 2010. By using the PTZ kindling epileptic rat SE model, the SD rats were divided into four groups:group B( PTZ+0. 9% sodium chloride solution),group C( PTZ+rHuEPO),group D(PTZ+LY294002+rHuEPO)and group E(PTZ+dimethyl sulfoxide+rHuEPO). Meanwhile,we assigned SD rats without SE model building into group A(0. 9% sodium chloride solution). The behavioral and EEG changes were detected;TUNEL was used to check the apoptosis status of hippocampal neurons;immunohistochemistry was used to observe the number of cells with positive p-Akt, Bax and XIAP;the RT - PCR method was used to detect the expression level of BaxmRNA in hippocampus;Western blot method was employed to detect the protein expression levels of Akt,p-Akt and XIAP. Results Compared with group B,group C was higher(P<0. 05)in the number of cells with positive p-Akt and XIAP,the protein expression levels of p-Akt and XIAP and was lower in the number of cells with positive Bax and the protein expression level of BaxmRNA. Compared with group C,group D was lower in the number of cells with positive p-Akt and XIAP and the protein expression levels of p-Akta and XIAP and was higher(P <0. 05)in the number of positive cells with positive Bax and the expression level of BaxmRNA. Conclusion rHuEPO can increase the number of cells with positive p-Akt and XIAP and the protein expression of p-Akt and XIAP. It can also decrease the number of cells with positive Bax and the expression level of BaxmRNA,reduce the apoptosis of hippocampal neurons,and has a neuroprotective effect. When PI3K inhibitor LY294002 is added,the number of cells with positive p-Akt and XIAP and the protein expression of p-Akt and XIAP decrease,the number of cells with positive Bax and the expression of BaxmRNA increase,the apoptosis of hippocampal neurons increases,and the neuroprotective effect of rHuEPO is weakened. Therefore,the signal path of PI3K/Akt may be one of the neuroprotective ways of rHuEPO. The possible mechanism may be that rHuEPO activating the PI3K/Akt increases the expression levels of p-Akt and XIAP,decreases the expression level of Bax,thus mediating the path of mitochondrial apoptosis and playing a neuroprotective role of anti-apoptosis and survival promotion.关键词
癫痫持续状态/重组人红细胞生成素/磷酸肌醇3-激酶类/蛋白激酶类/Bcl-2相关X蛋白质/X连锁凋亡抑制蛋白质Key words
Status epilepticus/Recombinant human erythropoietin/Phosphatidylinositol 3 - kinases/Protein kinases/Bcl-2-associated X protein/X-linked inhibitor of apoptosis protein分类
医药卫生引用本文复制引用
史志勤,卞红磊,魏艳静,尹晓琳,张荣,梁文杰,刘瑞春,王维平,于江华..重组人红细胞生成素对癫痫持续状态大鼠海马线粒体凋亡途径相关调控因子的影响及作用机制[J].中国全科医学,2015,(19):2310-2316,7.基金项目
河北省自然科学基金资助项目 （）
