卵巢去势引起神经细胞凋亡及凋亡相关蛋白改变与UPAN的作用

目的　通过观察去卵巢大鼠海马组织神经元凋亡相关蛋白的表达及用TUNEL试剂盒检测 ,研究缺乏雌激素是否引起神经元凋亡 ;评估UPAN是否能改善雌激素缺乏引起的凋亡 ,探讨雌激素缺乏引起神经细胞凋亡的机制与UP AN神经保护作用机制。方法　♂Wistar大鼠随机分 3组 :假手术组 (C组 ) ,卵巢去势对照组 (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组从卵巢去势第7wk开始用UPAN治疗 6wk ,用免疫组化和Westernblot观察AIF、Bax、Bcl 2的表达 ,并用TUNEL试剂盒检测。结果　免疫组化和Westernblot结果表明去卵巢大鼠海马组织AIF、Bax表达增加 ,Bcl 2表达减少 ,UPAN治疗组这些蛋白表达恢复到接近正常。在去卵巢大鼠海马组织和皮层存在大量的TUNEL阳性细胞 ,UPAN治疗组TUNEL阳性细胞比卵巢去势对照组明显减少。结论　去卵巢大鼠因雌激素缺乏引起神经细胞凋亡及凋亡相关蛋白改变 ,UP AN具有明显的治疗作用

OVX induced neuronal apoptosis and effects of UPAN on apoptosis-related protein changes in rats

AIM To observe the effect of UPAN(Underpeptide of App N Terminus) on neural apoptosis and expression of some proteins related with apoptosis in the hippocampus of ovariectomized rats. METHODS Female Wistar rats were randomly divided into three groups. The second group (OVX group) and the third group (UPAN+OVX group) were ovariectomized bilaterally and the first group(C group) underwent sham operation as control.From the seventh weeks after operation,the third group were injected with UPAN 3 5 μg/per rat, three times a week for six weeks. In the mean time, the OVX and C groups were given normal saline. Immunohistochemistry and Western blot were performed for detecting antibodies AIF,Bax,Bcl 2,and examining whether there exist apoptosis using TUNEL. RESULTS The number of apoptotic neurons was clearly higher in hippocampal and cortex in OVX group than UPAN+OVX group. Treating with UPAN markly decreased the apoptosis. Immunohistochemistry and Western blot showed that the expression of AIF and Bax increased in hippocamp neurons of OVX group. The expression of Bcl 2 decreased. Treatment with UPAN restored these changes. CONCLUSIONS The expression of apoptosis related proteins are abnormal in the OVX rats,UPAN can normalize these changes; Estrogen deficiency can induce neuronal apoptosis. UPAN can diminish apoptosis.