促红细胞生成素对血管性痴呆大鼠认知功能的影响及机制。

Influences and mechanism of erythropoietin on the cognitive function of vascular dementia rats.

机构信息

Department of Neurology, Hebei Medical University, Shijiazhuang, Hebei, China.

Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, China.

出版信息

Aging (Albany NY). 2023 Nov 6;15(21):12264-12274. doi: 10.18632/aging.205178.

DOI:10.18632/aging.205178

PMID:37934569

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10683607/

Abstract

PURPOSE

To investigate the influences and mechanism of erythropoietin (EPO) on the cognitive function of vascular dementia (VD) rats.

METHODS

Spatial memory capacity was assessed by Morris water maze test; 2) Pathological conditions of brain tissues were detected by hematoxylin-eosin (HE) staining; 3) The effect of treatment on apoptosis was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining; 4) Western blotting was used to examine the protein expression in hippocampal neurons.

RESULTS

The escape latency and swimming distance in the EPO group were much shorter than those in the Model group on the fifth day. In the spatial exploration test, the time spent in the target quadrant was longer, the number of platform crossings was larger and the swimming speed was higher in the Sham group and EPO group than those in the Model group. The results of HE staining showed that the cells in the hippocampal CA1 region were arranged closely in the Sham group, loosely and disorderly in the Model group but significantly better in the EPO group. Compared with that in the Model group, the number of apoptotic cells in the EPO group was obviously smaller. The results of Western blotting revealed that the expressions of EPO, p-EPOR, p-SHP2, p-TrKB, p-PI3K, p-ERK1/2 and Bcl-2 rose, while the expressions of P22, P47, Caspase-3, Caspase-9 and Bax significantly declined in the EPO group.

CONCLUSIONS

EPO can effectively ameliorate the cognitive dysfunction induced by chronic hypoperfusion in VD rats by mediating oxidative stress-related pathways.

摘要

目的

探讨促红细胞生成素（EPO）对血管性痴呆（VD）大鼠认知功能的影响及其作用机制。

方法

1）采用 Morris 水迷宫实验检测空间记忆能力；2）苏木精-伊红（HE）染色检测脑组织病理状况；3）末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）染色观察治疗对细胞凋亡的影响；4）Western blot 检测海马神经元蛋白表达。

结果

EPO 组大鼠在第 5 天的逃避潜伏期和游泳距离明显短于模型组。在空间探索试验中，Sham 组和 EPO 组在目标象限停留的时间更长，穿越平台的次数更多，游泳速度更快，而模型组则明显较差。HE 染色结果显示，Sham 组海马 CA1 区细胞排列紧密，模型组细胞排列疏松紊乱，EPO 组则明显改善。与模型组相比，EPO 组的凋亡细胞数量明显减少。Western blot 结果显示，EPO、p-EPOR、p-SHP2、p-TrKB、p-PI3K、p-ERK1/2 和 Bcl-2 的表达升高，而 P22、P47、Caspase-3、Caspase-9 和 Bax 的表达明显下降。