Protective Effects And Mechanisms Of Meloxicam On Chronic Aluminum Overload-Induced Neurodegeneration Of Rats

Objective To study the protective effects and mechanisms of meloxicam on neurodegeneration induced by chronic aluminum overload in rats.METHODS The neurodegeneration models of Wistar rats were established by intragastric administration of aluminum gluconate(200 mg Al3+/Kg)once a day, and 5 days every week for 20 weeks. Meloxicam1 mg.kg-1 and 3 mg.kg-1was intragastrically administered 30 min after each aluminum administration. Spatial learning and memory function of rat was determined by Morris water maze. Morphologic changes of hippocampal neurons were evaluated by HE staining. The activity of AchE, MAO-B and SOD and the content of MDA was detected by biochemistry enzymology. The changes of Aβ, APP, ChAT and TH expression in rat hippocampi was detected by immunohistochemistry, and COX-2, 5-LO mRNA and protein expressions in hippocampus were detected by RT-PCR and Western-blotting, respectively. The hippocampus metal ion level was detected by ICP-AES.Results The spatial learning and memory function of chronic aluminum overload rat was significantly impaired, and hippocampal neurons in model rat showed obviously karyopycnosis. The MDA content and the activities of AchE and MAO-B obviously increased, and the SOD activity significantly decreased. The Aβand APP expression protein obviously increased, and the ChAT and TH protein expression significantly decreased. The expression of COX-2, 5-LO mRNA and protein in hippocampi obviously increased. The increasing metal ion level of the hippocampus was also observed. Meloxicam1 mg.kg-1 and 3 mg.kg-1 obviously prevented rats from learning and memory function impairment induced by chronic aluminum overload, and neurons damage in hippocampus and significantly inhibited the increasing of AchE and MAO-B activities, and MDA content, and the decreasing of SOD activityies induced by aluminum overload in rats. Meloxicam obviously inhibited the over expression of Aβ, APP and the COX-2, 5-LO mRNA and protein,and the decreasing of ChAT, TH protein expression by chronic aluminum overload.The increase of metal ion level in the hippocampus by chronic aluminum overload was significantly inhibited by meloxicam.Conclusion Meloxicam has a protective effect on neurodegeneration induced by chronic aluminum overload in rats. The action of inhibiting COX-2 activity and decreasing the production of PGs may be involved in the protective mechanism of meloxciam.