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Effects Of Recombinant Ganoderma Lucidum Immunomodulatory Protein On A Rat Model Of Alzheimer’s Disease And Its Mechanism’s Studies

Posted on:2015-01-18Degree:MasterType:Thesis
Country:ChinaCandidate:J FuFull Text:PDF
GTID:2254330428485439Subject:Biochemistry and Molecular Biology
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Alzheimer’s disease (AD) is one of the most common diseases in the elderlyneurodegenerative. AD is a sick machine heterogeneous disease with characteristicneuropathological and neurochemical changes. Inducing factor for AD includeneuronal apoptosis, inflammatory cascade, oxidative stress, etc. So far, there are manyclinical drugs to treatment of AD, but there presence side effects, such as short effects,side effects and high prices. Therefore, there is a long way to develop an effectiveprevention and treatment of AD drug.Fungal Immunomodulatory Protein of Ganoderma lucidium (LZ-8) was aImmunomodulatory Protein isolated from extract of Ganoderma mycelium. Studieshad found that it has the biological activity of promoting peripheral lymphocyte andspleen cells proliferation. Induced animal and human macrophages secrete a variety ofcytokines and eliminate further defense against pathogens, maintaining the body’shealth. In this paper, the use of recombinant Ganoderma lucidum immunoregulatoryprotein (rLZ-8) was obtained from Pichia pastoris, by Professor Sun Fei, JilinUniversity.Immunomodulatory protein with high purity and high stability of activityrLZ-8samples. To explore whether the rLZ-8has the protect effective of AD.In this paper, Use intraperitoneal injection of scopolamine hydrobromide(1.5mg/kg/d) for7days to establish a rat model of AD. Water maze experiment wasperformed after each dose, detect the incubation period, swimming distance and thelast administration’s strategy to find the platform of the rats. Experimental resultsshow that compared with the saline group, rats in the model group was significantlyincreased latency and swimming distance (P<0.05, P<0.05), search platform strategyweakened, Prove that the AD model success.Based on the successful model, rats were randomly divided into saline group,AD model group, positive drug group, rLZ-8low, medium and high dose groups.Give drugs,Respectively, To the end of the experiment. Give Modeling drug on the8day. Serum and brain tissue taken after the end of the experiment rats were detected.Neurotransmitter acetylcholine (ACh) related to learning and memory, this paperuse colorimetric to detect the activity of AChE and ChAT in serum and brain. Theresults showed that, compared with the saline groupp, AChE activity of rats in the model group increased significantly (P<0.05), ChAT activity was significantlydecreased (P<0.05). The rLZ-8three dose groups could improve this change.Preliminary determination rLZ-8has protective effect on scopolamine-inducedlearning and memory on rats.Oxidative stress also induced one of the causes of AD, so this paper usescolorimetric enzymes regulating radicals were detected. Results are as follows: MAOactivity was significantly increased in model group (P<0.01), SOD, GSH-Px, ChATactivity was significantly decreased (P<0.05, P<0.01, P<0.05), MDA levels weresignificantly elevated (P<0.01). The rLZ-8inhibits oxidative stress occurs, preventingAD.Inflammatory cytokines and neurotrophic factors play an irreplaceable role inAD. To further study of the rLZ-8’s protective effect of AD, in this thesis, usingELISA test to detect the levels of TNF-α, IL-6on rats’ blood and brain tissue andBDNF, GDNF levels on rats brain tissue. Experimental results show rLZ-8oninflammatory factors and neurotrophic factors have a different regulation.Through these studies, preliminary evidence that rLZ-8exhibited protectiveeffect on AD model which induced by scopolamine. It’s a potential drug for clinicaltreatment of AD.
Keywords/Search Tags:Alzheimer’disease, recombinant Ganoderma immunomodulatory protein, animalmodels, scopolamine hydrobromide, Acetylcholine, oxidative stress, inflammatorycytokines
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