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目的观察重组人红细胞生成素对戊四氮所致的癫痫持续状态(statusepil epticus,SE)的SD大鼠海马神经元磷酸化Akt(p-Akt)表达的影响,并应用PI3K抑制剂LY294002进行干预,进一步探讨重组人红细胞生成素是否对SE大鼠的海马神经细胞具有保护作用及作用的可能机制。方法采用戊四氮点燃大鼠SE模型。75只SD大鼠随机分为5组(n=15),A组:正常对照组(腹腔注射生理盐水);B组:生理盐水治疗组(腹腔注射戊四氮点燃SE发作后30分钟,再腹腔注射生理盐水);C组:重组人红细胞生成素治疗组(腹腔注射戊四氮点燃SE发作后30分钟,再腹腔注射重组人红细胞生成素);D组:PI3K抑制剂LY294002干预组(腹腔注射戊四氮点燃SE发作后10分钟,再脑室内注射LY294002,SE发作后30分钟腹腔注射重组人红细胞生成素);E组:DMSO(二甲基亚砜)对照组(腹腔注射戊四氮点燃SE发作后10分钟,再脑室注射LY294002的溶剂DMSO,SE发作后30分钟腹腔注射重组人红细胞生成素),检测各组大鼠行为、脑电图的改变及HE染色观察各组海马病理学的改变、免疫组织化学法观察各组磷酸化Akt的表达。结果重组人红细胞生成素治疗组较生理盐水治疗组磷酸化Akt的表达增多;PI3K抑制剂LY294002干预组海马磷酸化Akt表达较重组人红细胞生成素治疗组减少。结论重组人红细胞生成素对SE大鼠的海马神经元具有保护作用,其作用机制可能是重组人红细胞生成素提高了Akt的活性,激活了存活通路PI3K/Akt途径,这可能是重组人红细胞生成素发挥神经保护作用的机制之一。
Objective To observe the effect of recombinant human erythropoietin on phosphorylation of Akt (p-Akt) in hippocampal neurons of SD rats induced by pentylenetetrazol (STAT), and to investigate the effect of PI3K inhibitor LY294002 , To further explore whether recombinant human erythropoietin can protect the hippocampal neurons of SE rats and its possible mechanism. Methods Pentylenetetrazole was used to light the rat SE model. Seventy-five SD rats were randomly divided into 5 groups (n = 15). A group: normal control group (intraperitoneal injection of saline); B group: saline treatment group (intraperitoneal injection of pentylenetetrazole ignited 30 minutes after onset of SE, Intraperitoneal injection of saline; group C: recombinant human erythropoietin treatment group (intraperitoneal injection of pentylenetetrazole-lit 30 minutes after the onset of SE, and then intraperitoneal injection of recombinant human erythropoietin); D group: PI3K inhibitor LY294002 intervention group Injection of pentylenetetrazole ignited SE 10 minutes after the onset of SE, and then intracerebroventricular injection of LY294002, SE 30 minutes after the onset of intraperitoneal injection of recombinant human erythropoietin); E group: DMSO (dimethyl sulfoxide) control group (intraperitoneal injection of pentylenetetrazol 10 minutes after the onset of SE, solvent DMSO of LY294002 was intravenously injected into the brain, and recombinant human erythropoietin was intraperitoneally injected 30 minutes after the onset of SE). The changes of behavior, EEG and HE staining were observed in each group of hippocampal pathology The changes of phosphorylated Akt in each group were observed by immunohistochemistry. Results The expression of phosphorylated Akt was increased in the rhEPO treatment group compared with the saline control group. The phosphorylation of Akt in hippocampus was decreased in the PI3K inhibitor LY294002 group compared with the rhEPO treatment group. Conclusion Recombinant human erythropoietin can protect the hippocampal neurons of SE rats. The mechanism may be that recombinant human erythropoietin can increase the activity of Akt and activate the PI3K / Akt pathway, which may be the result of recombinant human erythropoiesis One of the mechanisms by which neurones play a neuroprotective role.