| Objectives To investigate the effect of dl-3-n-butylphthalidle(NBP)On the influence of learning and memory ability,the expression of NF-κB,P38,IL-1βand the ultrastructure in hippocampal region in rats with Alzheimer’s disease(AD),and then investigate the mechanidm of neuroprotectin from NBP.Methods 1 36 male Sprague-Dawley rats were divided into sham operation group(Sham group,n=12),AD model group(AD group,n=12)and butylphthalide group(group NBP,n=12).2 Animal models of AD group and the Treatment group were established with 5ug beta-amyloid 1-42 by Stereotactic microinjection of bilateral hippocampus,and the Sham group with equel sailine.3 After 4 weeks,Morris water maze experiment were tested,compared by escape latent period and numbers of cross platform of rats in three groups.Then the treatment group were given NBP mixed with cooking oil at the ratio of 8mg:1ml in the dose of 1ml/100 g per rat by intragastric administration,and the Sham group and the AD group treated oniy by the same dose of cooking oil,2 times a day.4Another 2 weeks later,Morris water maze experiment were tested again to detect the ability of learning and memory of rats in these three groups.5 The learning and memory abilities of rats were detected by the Morris water maze.Cell morphological change and calculate the neuronal density were observated under the HE staining hippocampal CA1 area in this region;the expression of NF-κB,P38,IL-1β by immunohistochemical staining;The change of ultrastructure of rats in hippocampal CA1 region were observed by electron microscope.Results 1 In the forth week,Morris water maze experiment showed that compared with the Sham group,escape latent period of rats in the AD group and the NBP group(NBP group)prolonged significantly(P<0.05),the number of cross platform in the two groups reduced(P<0.05).Compared with the AD group,there was no statistically significance in escape latency period and the number of cross platform in the NBP group(NBP group)(P>0.05).At 6th week,Morris water maze experiment showed that compared with Sham group,escape latent period of rats in the AD group and the NBP group prolonged significantly(F < 121.71,P<0.05),the number of cross platform in the two groups reduced(P < 0.05).Compared with the AD group,escape latent peroid of rats in the NBP group(NBPgroup)shorten significantly(P<0.05),whereas the number of cross platform of rats in the NBP group exceeded obviously(P<0.05).The comparison of the results of Morris water maze data of rats at 6 weeks and 4 weeks shows that: there was no significance between the difference of escape latency and the difference about the requency of crossing the original platform in the sham group(P > 0.05).Compared with AD group,the difference of escape latency in NBP group was statistically significant(P<0.05).Compared with the AD group,the requency of crossing the original platform increased in NBP group,the difference between the two groups was statistically significant(P<0.05).2 The HE staining shows that,there was no significant change in cell morphology in Sham group.In AD group,the pathological changes were obvious,and the pyramidal cells in the CA1 area of the hippocampus were irregular,and the cell loss and apoptosis occurred.On the contrary,the number of pyramidal cells in NBP group was more than that of AD group,the cell arrangement was relatively neat,and the morphology of the cells was less than that of AD.Hippocampal CA1 area neuron density was found that,compared with the Sham group,both the AD group and the NBP group,the neuron density was lower,there was a significant difference between the two groups,and the difference was statistically significant.Compared with AD group,the density of hippocampal CA1 neurons was found to be higher than that of group NBP,and the difference between the two groups was statistically significant(P<0.05).3 The immunohistochemical staining results showed that compared with the Sham,the NF-κB,P38,IL-1β positive cell of hippocampal CA1 region of rats in the AD group and the NBP group(NBP group)increased significantly(P<0.05);compared with the AD group,the NF-κB,P38,IL-1β positive cell of the hippocampal CA1 region of rats in the NBP group(NBP group)lowered(P<0.05).4 Under the transmission electron microscopy(sem)Sham group of hippocampus CA1 area neurons are circular or ovoid,big nucleus and organelles.AD group in the rat hippocampus CA1 area neurons in the nucleus shape is irregular,organelles show is not clear,the structure damage,number decreased significantly.Compared with the AD group,NBP group of hippocampus CA1 area neurons damage is lighter.Conclusions 1 NBP has protective effects on AD model rats,which can improve the ability of learning and memory,reduce the damage of pathological tissue and ultrastructure.2 NBP can decrease the expression of P38,NF-kappa B and IL-1 beta positive cells in the hippocampal CA1 area of AD.3 The protective effect of NBP may be to reduce the activity of P38 and NF-kappa B,so as to decrease the activity of IL-1beta,which can control the expression of inflammatory mediators... |
PDF Full Text Request