| Objective:Study the possible mechanism of recombinant human erythropoietin(rh EPO) to improve the cognitive function of vascular dementia rats. Methods:By Morris water maze qualified after screening, forty clean male SD rats were randomly divided into five groups : the Sham group, the 2VO group, the 2VO + rh EPO group, the 2VO +rh EPO + AG490(Janus kinase 2 inhibitor)group and the 2VO + AG490 group,each group eight,The bilateral occlusion of common carotid arteries in SD rats was adopted to established the vascular dementia model; all groups rats respectively were disposed by intraperitoneal injection of AG490(5mg/kg) or the same quantity of DMSO-AG490 solvent after chronic ischemia for 3 days. after 30 minutes, all groups rats respectively undergone intranasal delivery rh EPO at the dose of 150U/125μl or equivalent volume of saline at the sametime; administered once a week, for a total of eight times.After the 8 weeks, the Morris water maze was explored to observed the spatial learning and memory capability.Morphology changes of cerebral cortex and hippocampal CA1 nerve cells were observed by HE and electron microscopy to observe the ultrastructure of hippocampal neurons in each group. Results:1 Behavioral tests results showed :(1) place navigation experiment : The shorter the escape latency, the stronger the animals get the learning ability.With the increase of training days, each group rats the mean escape latency was significantly shortened.The average escape latency period in 2VO + rh EPO group was lower than that in 2VO group, 2VO + rh EPO + AG490 group, and the 2VO+ AG490 group and the differences were statistically significant(P﹤0.05),Compared with the Sham group There was no statistically significant difference(P﹥0.05).(2) Space exploration experiment:1) The more the number of cross-platform, the stronger the animals got the memory ability.the number of cross-platform in 2VO + rh EPO group was obviously higher than that of 2VO group,2VO + rh EPO + AG490 group, 2VO + AG490 group and the differences were statistically significant(P < 0.05),Compared with the Sham group There was no statistically significant difference(P﹥0.05). 2﹚Target quadrant residence time:the longer the target quadrant residence time, the stronger the animals got the memory ability. The results showed : The results showed that there was no statistical significance in comparison between 5 groups respectively(P﹥0.05).HE Showed: In Sham group, Cells were ordered in the hippocampal CA1 area,Normal cells form, a large number of pyramidal cells could be seen in cortex,Where the nucleis and axons were visible clearly, it was rich in nissl body; In 2VO group, the cells of hippocampal CA1 area were disordered, the cell body contraction, nuclear hyperchromatic, nucleus pycnosis and nuclear dissolved could be Visible,Cortex pyramidal cells scattered,Where the axon had disappeared;In the 2VO + rh EPO group, relatively, the cells of hippocampal CA1 area arranged neatly, and the cell structure closed to normal cells,a few of contractible cells could be seen occasionally,there were many Cortex pyramidal cells, axons and nucleus were clear.morphological changes of hippocampal CA1 area and cortex nerve of the 2VO + rh EPO + AG490 group and the 2VO+ AG490 group were similar to 2VO group.Electron microscopy showed: the cell outline was clear and nuclear Chromatin evenly distributed, cell organelles were rich in mitochondria, rough endoplasmic reticulum and free ribosome and golgi complexes in the Sham group; the cell outline was fuzzy,the heterochromatin showed multiple high-density block distribution;Around the nucleus,the Organelles had reduced, collapsed and disappeared In the 2VO group;the cell outline was clear yet,nuclear Chromatin appeared to be irregular high-density dotted distributed,It was Visible that part swelling, cavitation mitochondria, mild expansion of rough endoplasmic reticulum,the primary and secondary lysosomes could be seen in the cytoplasm In the 2VO + rh EPO group; The cell ultrastructure changes of the 2VO + rh EPO + AG490 group and the 2VO+ AG490 group were similar to the 2VO group. Conclusions:intranasal administration of rh EPO could improve cognitive function in rats with vascular dementia and its action mechanism may be related to activation of JAK2- STAT3 pathway. |
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