Change Of PGs Synthase-PGs-PGs Receptor Signal Pathway In Aluminum-overload Rat Brain

Aim: To observe the change of PGs synthases-PGs-PGs receptorssignal pathway in rat cortex and hippocampus induced by chronicaluminum overload.Methods:1.34SD male rats were randomly divided into two groups: controlgroup and aluminum-overload group. Rats in aluminum-overload groupwere intragastric administered with aluminum gluconate（Al3+0.2g·kg-1·d-1）5days a week for20weeks to establish rat model of chronicaluminum-overload brain damage. Rats in control group were intragastricadministered with sodium gluconate.2. Morris water maze was used to evaluate spatial learning andmemory ability of rats. HE staining was used to evaluatepathomorphological change of rat cortex and hippocampus neuron.Biochemical method was used to detect the SOD activity and MDA content.PGs content of rat cortex and hippocampus was measured by the method ofELISA. Rat cortex and hippocampus PGs synthase and receptor mRNA expression was detected by RT-PCR as well as protein expression wasdetected by Western-Blotting.Results:1．Compared with that of control group, the spatial learning andmemory ability of rat was significantly impaired and rat cortex andhippocampus neuron showed obviously nuclear pyknosis inaluminum-overload group. Aluminum overload caused a significantincrease of MDA content and a decrease of SOD activity in rat cortex andhippocampus.2. Change of PGDS-PGD₂-DP receptor signal pathway:Compared with that of control group, the H-PGDS mRNA expressionin cortex was increased and was decreased in hippocampus inaluminum-overload group. But there was no significance.PGD₂content in rat cortex and hippocampus was significantlyincreased in aluminum-overload group.In aluminum-overload rat cortex, the mRNA expression of DP1receptor was significantly increased, but not the protein expression. Inaluminum-overload rat hippocampus, the mRNA and protein expression ofDP1receptor were obviously increased.3. PGES-PGE₂-EP receptor signal pathway:Compared with that of control group, the mPGES-1mRNA expressionwas obviously increased in aluminum-overload rat cortex and hippocampus.In aluminum-overload group, the cPGES mRNA expression wasdecreased in cortex and was increased in hippocampus. But there was nosignificance.PGE₂content was significantly increased in aluminum-overload ratcortex and hippoampus.In aluminum-overload group, the EP1mRNA expression wasincreased in cortex and was decreased in hippocampus, but there was nosignificance.In aluminum-overload rat cortex and hippoampus, the EP2mRNA andprotein expression were obviously increased.In aluminum-overload rat cortex and hippoampus, the EP3mRNA andprotein expression were obviously decreased, and the EP4mRNAexpression were obviously increased.4. PGFS-PGF_2α-FP receptor signal pathway:Compared with that of control group, PGF_2αcontent were markedlyincreased in aluminum-overload rat cortex and hippocampus.In aluminum-overload rat cortex, the FP mRNA expression wereobviously decreased, but not the protein expression. In aluminum-overloadrat hippocampus, the FP mRNA and protein expression were obviouslydecreased.5. PGIS-PGI₂-IP receptor signal pathway: Compared with that of control group, the PGIS mRNA expression,6-keto-PGF_1αcontent, and the IP mRNA and protein expression wereobviously increased in aluminum-overload rat cortex and hippocampus6. TXAS-TXA₂-TP receptor signal pathway:Compared with that of control group, the TXAS mRNA expressionwas significantly increased as well as TXB₂content in aluminum-overloadrat cortex and hippocampus.The TP mRNA expression was significantly decreased inaluminum-overload rat cortex and hippocampus, but not the TP proteinexpression.Conclusions:There is an imbalance of PGs synthases-PGs-PGs receptors signalpathway in chronic aluminum-overload rat cortex and hippocampus. Theimbalance may be involved in mechanism of brain damage induced bychronic aluminum overload.