The Protective Effect And Mechanism Of Meloxicam On Cognitive Impairment In Diabetic Rats

Objective: To investigate the protective effect of meloxicam on cognitive impairment in diabetic rats and its possible protective mechanism.Methods: SD male rats were fed with high-fat diet for 1 month,then the rats were injected with streptozotocin(40 mg/kg,i.p.)to establish a diabetic rat model.After the diabetic rat model was established successfully,the rats were fed with high-fat diet for another month and then given meloxicam 0.9 mg/kg and 2.7 mg/kg for 2 months.The changes of blood glucose and body weight of rats were monitored,the plasma levels of TG,TC and LDL-C in rats were detected by chemical kits.Spatial learning and memory abilities of rats were measured by Morris water maze.The morphological changes of hippocampus and cortex neurons were observed by HE staining,and the number of microglia in the cortex was detected by immunohistochemistry.Plasma insulin level and contents of TNFα,IL-6,CRP,PGE2 and cAMP in hippocampus and cortex of the rats were detected by ELISA.Western blot was used to detect the protein expressions of APP,Aβ,COX2,EP1,EP2,EP3,EP4 and pPKA in rat hippocampus and cortex.Results: Compared with the normal group,the blood glucose of diabetic rats were significantly increased and their body weights were decreased.The plasma levels of TC and TG in diabetic rats were significantly increased,while the plasma level of LDL-C had no significant change.The plasma insulin level was significantly decreased.In diabetic rats,the spatial learning and memory abilities were significantly decreased,the hippocampus and cortex neurons showed significantly karyopyknosis.The contents of TNFα,IL-6,CRP,PGE2 and cAMP were significantly increased,and the protein expressions of APP,Aβ,COX2,EP1 and EP2 were significantly increased.The protein expression of pPKA was significantly decreased,while protein expression of EP4 had no significantly change.Compared with the model group,administration of meloxicam had no significant effects on body weight,blood glucose,TC,TG and plasma insulin level in diabetic rats.Meloxicam could significantly improve the spatial learning and memory abilities of diabetic rats with cognitive dysfunction,reduce the damage of hippocampus and cortex neurons,and decrease the contents of TNF α,IL-6,CRP,PGE2 and cAMP.At the same time,meloxicam could not only significantly reduce the expressions of APP,Aβ,COX2,EP1 and EP2 but also increase the expressions of EP3 and pPKA in diabetic rats.Conclusion: Meloxicam has a protective effect on neuronal injury in diabetic rats,and its mechanism may be associated with reconstructing the balance of COX2-PGE2-EPs-cAMP/PKA signaling pathway.