The Pathological Impact Of Icariin On Dementia Model Mice And Related Mechanism

Alzheimer’s disease(AD) is a kind of nervous system degenerative disease with the features of hiding onset and progressive development,and etiology is unknown yet. “Aβ theory”the most widely accepted theory of Alzheimer’s disease(AD), According to this explanation, amyloid-β protein(Aβ)is the most main reason of Alzheimer’s disease(AD). Aggregation of Aβ in the particular area of the brain can lead to a series of pathological changes(Death of neurons, Neurofibrillary tangles, Oxidative stress and Damage of cholinergic system). In recent years, studies have found that progranulin(PGRN) have close relationships with AD and Aβ. There is some quantitative relation between PGRN and Aβ, which is involved in a series of physiological processes of AD, but the specific mechanism of PGRN in the pathogenesis of AD is still unclear.Icariin(ICA) is the main active ingredient of the Berberidaceae Epimedium genus Epimedium plants and the major pharmacologival effects of ICA reproductive and endocrine. In recent years, more and more attention has been paid to the role of ICA in the nervous system, which has obtained a certain research results, and its effect on the treatment of AD is still relatively fewer.In this study, we used Aβ1-42 to induce AD mice model and ICA to treat the mouse. Then,we observed the impact of ICA on Aβ deposition, Neural tangles, Oxidative stress and Damage of cholinergic system, which are the typical features of AD pathology and discussed the quantity variation of PGRN in mouse hippocampus. This study layed a foundation for further study of the effect of ICA on AD treatment and the mechanism of PGRN in AD pathogenesis.Methods:Mice were divided into four groups, including control group(Naive), normal saline group(NS), model group(Aβ) and the treatment group, the treatment group was divided into three groups, respectively ICA30, 60 and 120mg/kg groups.The model group and treatment group mice bilateral hippocampal injection of oligomeric state Aβ1-42 in dementia model, with amount of normal saline instead of physiological saline group, control group don’t do processing.Modeling the next day,the treatment group, ICA30,60 and 120mg/kg gavage,the other group with alternative equivalent physiological saline, materials for 14 consecutive days.HE staining, observe the changes of hippocampal morphology in mice.Elisa test mice hippocampus within A β1-42, AChE and ChAT content.The hippocampus in mice were tested by immunohistochemical method in Aβ1-42 deposition and the expression of tau protein, PGRN and CDK5.The contents of SOD, GSH-PX and NOS in hippocampus of mice in the test kit.Western blot detect the expression of tau protein, CDK5 and OGRN.Results:Effects of ICA on the pathology of Alzheimer’s disease model miceThe results of HE:Compared with the control group and saline group, model group mice hippocampus inflammatory injury obviously, neuronal degeneration and cell shrinkage, cell bodies and the surrounding tissue from, the nucleus pycnosis, treatment group was improved.The results of Elisa:Aβ1-42 content of model group was obviously increased, and the control group and saline group almost undetectable Aβ1-42 deposition, the treatment group compared with model group Aβ1-42 content declined.Model group compared with control group and saline group AChE and ChAT content decreased obviously, the treatment group was increased.The results of SOD and gsh-px kit test:Model group compared with control group and saline group content of SOD and gsh-px decreased obviously, the treatment group was increased.The results of Immunohistochemical:Groups are observe no obvious Aβ1-42.The results of Western blot:Model group compared with control group and saline group tau protein and CDK5 content increased significantly, the treatment group declined.Related mechanisms(1)The results of Immunohistochemical:Model group compared with control group and saline group PGRN content increased significantly, the treatment group declined.(2)The results of Western blot:Model group compared with control group and saline group PGRN content increased significantly, the treatment group declined.Conclusions:1.Aβ1-42 can induce a series of pathological features of Alzheimer’s disease(nerve fiber entanglement, oxidative stress, cholinergic system damage) in the hippocampus of mice.2. Icariin treatment can reduce the AD model mice pathology with dose dependent. This improvement may be realized through accelerating the clearance of amyloid beta, inhibiting tau phosphorylation, enhancing the activity of acetylcholinesterase and choline acetyltransferase and decreasing oxidative stress reaction.3. A beta deposition can increased the expression of PGRN, Icariin treatment can significantly reduce the expression of PGRN with dose dependent, this study suggests that PGRN may be related to the pathology of AD, which provides a new way of thinking for the pathogenesis of AD.