App17肽防治去卵巢大鼠海马神经细胞的凋亡

Neuronal apoptosis and the change of apoptosis-related proteins in ovariectomied rats and the effect of App17-mer peptide

目的 :观察去卵巢大鼠几种神经元凋亡相关蛋白的表达 ,并用TUNEL试剂盒检测 ,研究缺乏雌激素是否引起神经元凋亡 ;评估App17肽是否能改善去卵巢大鼠的神经细胞凋亡 ,初步探讨App17肽的神经保护作用机制。方法 :雌性Wistar大鼠随机分 3组 :假手术组 (shamcontrol组 ) ,卵巢去势对照组 (OVX组 ) ,App17肽实验组 (17P+OVX组 )。Sham组做假手术 ,OVX组和 17P +OVX组做双侧卵巢切除术。 17P +OVX组从卵巢去势第 7周开始用App17肽治疗 6周 ,用免疫组化和Westernblot方法观察AIF、Bax、Bcl- 2的表达 ,用TUNEL法检测凋亡情况。结果 :免疫组织化学和Westernblot结果表明App17肽实验组AIF、Bax表达明显少于去卵巢组 ;Bcl- 2在App17肽实验组的表达明显高于去卵巢组。TUNEL结果表明App17肽实验组凋亡细胞明显少于去卵巢组。结论 :雌激素缺乏引起去卵巢大鼠海马和皮层神经细胞凋亡相关蛋白改变和出现凋亡细胞 。

AIM: To observe the expression of apoptosis-related proteins in hippocampal neurons of (ovariectomized) (OVX) rats and explore the neuroprotective mechanism of the App17-mer peptide. METHODS: Female Wistar rats were randomly divided into three groups. Bilaterally ovariectomized rats with injection of App 17P peptide (3.5 μg in 0.1 mL/per rat, three times a week) formed the experimental group (17P+ OVX group). Anti-AIF, Bcl-2 and Bax antibodies were applied in the immunohistochemistry experiment. TUNEL was employed to detect apoptosis. RESULTS: The number of apoptotic neurons was clearly higher in hippocampal and cortex in OVX group than that in OVX+17P group. Immunohistochemistry demonstrated the increased expression of AIF, Bax in hippocampal neurons of OVX group. OVX group showed a significantly reduced expression of Bcl-2 in hippocampal neurons. Hippocampal tissue from OVX group showed the increased expression of AIF, Bax, and showed diminished expression of Bcl-2, treating with App17-mer peptide normalized the expression of these proteins. CONCLUSIONS: The expression of apoptosis-related proteins were abnormal in the OVX rats, App17-mer peptide normalized these changes. Estrogen deficiency induced neuronal apoptosis, and App17-mer peptide diminished apoptosis.