The Investigation Of Antiinflammation Of Atorvastatin On AD Rat Mode Induced By Aβ_1-42

Objective:To investigate the effect of antiinflammation of atorvastatin on theβ-amyloid 1-42(Aβ_1-42)-induced Alzheimer′s disease(AD)rat model.Research the protection on cognitive dysfunction,shape change in hippocampus and the emergence of inflammatory factor(IL-1β,IL-6,TNF-α)in hippocampus,and reveal protective mechanism of atorvastatin from anti-inflammatory aspects.Methods:Sixty healthy male Wistar rats(weight 250g-300g)were randomly divided into four groups.Aβ_1-42(sigma products)solution was diluted to 5ug/ul with sterile saline, and then incubated for 72 h at 37℃,rendering aggregation state of Aβ_1-42.Rats model were established via intracerebroventricular injected with Aβ,and then were given atorvastatin (5mg/kg/d)for the treatment group,with saline for the control group.Water Maze were used to observe learning and memory ability changes in rats,and expression of inflammatory cytokines IL-1β,IL-6 and TNF-αin the hippocampus were also detected by immunohistochemical technique.Furthermore,HE staining patterns,hippocampus neurons and glial cells in the small ultrastructural changes were observed under the light microscopy and electron microscopy respecitively.Results:1.Effects of atorvastatin on cognitive ability of AD rats modelDuring Morris Water Maze test,the escaping latency in 4 groups decreased gradually. Recorded the fifth day and statistically analyze them.Comparing with control group,the escaping latency in AD model group significantly extended(41.3±3.4s),the percentage of time in the platform quadrant markedly increased(21.20±1.28%),and the times of crossing platform quadrant markedly increased(3.6±1.517)(P＜0.01).Comparing with AD model, the escaping latency in statins treatment group was shortened(15.7±1.6s),the percentage of time in the platform quadrant(38.80±2.59)and the times of crossing platform quadrant (7.2±1.789)increased(P＜0.01).Statins control group compared with the control group, there was no significant difference.2.Pathological and ultrastructure changes of hippocampus of rats in each groupHE staining:one week later,hippocampal neurons in the control group were round and formed in order;the nucleus were clear and homogeneously stained.The lays of hippocampal neurons in AD group significantly decreased.The cells formed sparsely and the nucleus were deeply stained,which looked like triangle.The cells formed sparsely and the nucleus were deeply stained,which looked like triangle.Many gliacells proliferated around the hippocampus.In stains treatment group,the neurons and the nucleus just looked the same as in AD model group.The gliacell proliferation markedly abated.AMD SEM:In control group,most neurons have normal structure,and have rich cell organ;The nuclear is circle and mostly is euchromatin.In statins control group the majority of neurons are normal.Most of the model group neurons entropy;cells are pyknosis,have oval-shaped nucleus and the cell golgi's apparatus and endoplasmic reticulum are swelling, mitochondrial matrix with low electron density,cytoplasmic matrix with high electron density,cytoplasm is full of ribosome.There are more Glial cells than normal group. Myeloid body is seen in the cytoplasm.Compared with the model group,there are less recession neurons,glial cells in statins treatment group and the neuronal damage is lighter.3.Immunohistochemical staining to detecte inflammatory cytokine IL-1β,IL-6 and TNF-αexpression in rat hippocampusCompared with the control group,there are more three proinflammatory cytokines IL-1β,IL-6,TNF-α-positive cells in statins treatment group(P＜0.01);the kind of proinflammatory cytokines positive cells reduce in statin treatment group compared with the model group(P＜0.01);The difference is not statistical significance in control group and the statins control group-the positive cells are less in both group.Conclusion:1.Statins control group and the control group showed no significant difference in the results,so atorvastatin itself have no special effects on normal brain tissue.2.It was found that after atorvastatin treatment,nerve cell injury and gliosis were reduced under optical microscopy and electron microscopy in hippocampus.Learning and memory ability improved significantly.3.After atorvastatin treatment,six hours after intracerebroventricular injection proinflammatory cytokines IL-1β,IL-6,TNF-αsecretion decreased in hippocampus significantly compared with AD rat model group.One week later,IL-1β,IL-6,TNF-αsecretion is less than the six hours in the model group and the statins treatment group,but after atorvastatin treatment proinflammatory cytokines has still markedly decreased compared to the model group.