UPAN改善去卵巢大鼠海马神经元存活信号转导通路中信号转导蛋白的表达

Neuronal apoptosis and the change of signal transduction pathway in OVX rats with the effect of App_(63-73)

目的 通过观察去卵巢大鼠海马组织神经元存活信号转导通路中几个相关蛋白的表达情况 ,研究缺乏雌激素是否引起神经元病变 ;评估UPAN(APPN端 11肽、App63 73 )是否能改善雌激素缺乏引起的这种病变。 方法 雌性Wistar大鼠 ,随机分 3组 :假手术组 (C组 ) ,去卵巢对照组 (OVX组 ) ,UPAN治疗组 (UPAN +OVX组 )。C组做假手术 ,OVX组和UPAN +OVX组做双侧卵巢切除术。UPAN +OVX组从去卵巢第 7周开始用UPAN治疗 6周 ,用免疫组化方法观察Akt、cAMP应答元件结合蛋白 (CREB)的表达 ;免疫印迹法检测Akt、CREB、磷酸化cAMP反应结合蛋白 (pCREB)的表达。 结果 免疫组化结果表明去卵巢大鼠海马组织Akt/PKB ,CREB表达减少 (P <0 0 5 ) ,UPAN治疗组Akt/PKB ,CREB表达比去卵巢组明显增加 (P <0 0 5 )。免疫印迹法检测结果表明去卵巢大鼠海马组织 pCREB表达减少 ,UPAN治疗组pCREB表达比去卵巢组明显增加。 结论 去卵巢大鼠因雌激素缺乏引起海马神经元存活信号转导通路障碍 ,UPAN有明显治疗作用。

Objective Observing the expression of signal transduction pathway-related proteins in hippocampal neurons of ovariectomized rats can indicate that whether lack of estrogen can cause neuronal apoptosis ,and observing the effect of UPAN,and gain some insight into the neuroprotective mechanism of UPAN. Methods Female Wistar rats were randomly divided into 3 groups. Bilateral ovariectomized rats with injection of UPAN 3.5ug in 0.1 ml/per rat, three times a week,formed the experimental group(UPAN+ OVX group). Immunohistochemistry was done with antibodies of Akt and CREB.Western blot was done with antibodies of Akt,CREB,pCREB. Results Immunohistochemistry and Western blot showed that the expression of Akt and CREB was decreased in hippocampal neurons of OVX group, and treating with UPAN can restore the changes above mentioned. Western blot showed that the expression of Akt,CREB,pCREB was decreased in hippocampal neurons of OVX group,treating with UPAN can restore the changes above mentioned. Conclusions The expressions of signal transduction pathway-related proteins are abnormal in the OVX rats,UPAN can normalize these changes.