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Protective Effect of Misoprostol on Neurodegeneration Induced by Chronic Aluminum Overload in Rats

Author: GuoYuanXin
Tutor: YangJunQing
School: Chongqing Medical University
Course: Pharmacology
Keywords: Misoprostol prostaglandin prostaglandin sythase prostaglandinreceptors neurodegeneration
CLC: R965
Type: Master's thesis
Year: 2013
Downloads: 18
Quote: 0
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Abstract


Objective To investigate the protective effect of misoprostol onneurodegeneration induced by chronic aluminum overload in rats.Methods Sprague-Dawley rats were administered intragastricallyaluminum gluconate（Al3＋200mg/kg）,once a day,5days a week, for20weeks. Misoprostol (30,60and120μ g·kg-1) was intragastricallyadministered2hours after each aluminum administration. Spatial learningand memory function of rats was observed by Morris Water Maze.Histopathological changes of cortex and hippocampal neurons weredetermined by HE staining. The SOD activity and MDA content in ratcortex and hippocampus was evaluated by biochemistry enzymology. Thealteration of PGE2content in rat cortex and hippocampaus was detected byenzyme-linked immunosorbent assay (ELISA). The changes of mPGES-1,EP2, EP3and EP4mRNA expression in rat cortex and hippocampus weredetected by Real-Time PCR.Results The spatial learning and memory function of chronicaluminum overload rat was notablely impaired, the cortex and hippocampalneurons in aluminum overload rat showed remarkablely karyopycnosis. The SOD activity obviously decreased, the MDA and PGE2contentsignificantly increased. The expression of mPGES-1、 EP2and EP4mRNA in cortex and hippocampus notablely increased, and the expressionof EP3mRNA remarkablely decreased. Misoprostol significantly improvedthe spatial learning and memory function of aluminum overload rats, andobviously prevented the cortex and hippocampal neurons fromkaryopycnosis and loss. Misoprostol also remarkably increased the activityof SOD, decreased the content of MDA and PGE2in aluminum overlaod ratcortex and hippocampus, and caused a significantly up-regulation of EP3mRNA expression and a down-regulation of mPGES-1、EP2and EP4mRNA expression in aluminum overload rat cortex and hippocampus.Conclusions Misoprostol has a protective effect on neurodegenerationinduced by chronic aluminum overload in rats. The neuroprotectivemechanism of misoprostol may involve in stimulation of EP3andreconstruction of the balanced of PGES-PGE2-EP signal pathway.

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