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Experimental Study On The Protective Mechanism Of Jiannao Recipe On Mitochondrial Damage In Rats With Hypoxia-induced Cognitive Dysfunction

Posted on:2018-06-14Degree:MasterType:Thesis
Country:ChinaCandidate:Q WuFull Text:PDF
GTID:2354330515991947Subject:Diagnostics of Chinese Medicine
Abstract/Summary:PDF Full Text Request
BackgroundCognitive dysfunction(CI)refers to a status of cognitive function in different degree damage.People who get heavy CI is known as various types of dementia,and the light CI is known as mild cognitive dysfunction.In TCM literature records,there is no specific cognitive dysfunction.According its clinic manifestations,such as memory loss,cognitive dysfunction can be ascribed to TCM "amnesia","dementia".The disease of dementia is in the head of the brain,the positive qi is deficient in the present,the poison evil is stopped as the standard,its basic disease machine is the false standard,the immaterial inclusion.According TCM treatment method,prevention before disease,and treatment before it changed.The treatment of CI is using SZJ method,which can beneficial qi and blood.When body is under oxygen-poor,mitochondrial respiratory chain electron transport and oxidative phosphorylation obstacles occur,resulting in the electron transport chain lower enzyme activity inhibition,oxidative phosphorylation influences,decrease ATP synthesis,and increase the produce of free radicals.All of these results can damage cells,let the amount of synapsis decreases,nerve conduction velocity decreases,neuron necrosis or apoptosis.Therefore,a decline in clinical cognitive function.Preliminary experimental study had found that SZJ components can obviously improve A? of human neuroblastoma cell lines induced by nerve toxicity,and can effectively improved the behavior of AD model rats.This research was based on previous research.Cognitive dysfunction rats model was established by a lack of oxygen.Under the treatment of SZJ,looking at the difference of rats learning and memory ability,beta amyloid precursor protein(?APP)content and beta amyloid protein(A?1-42).8 hydroxyl content of deoxyguanosine(8-OHdG)was used as a marker detection the damage of mitochondrial DNA.Preliminary discussion SZJ protection mechanism of mitochondrial injury rats.Brain mitochondrial injury and the correlation between the zang-fu organs mitochondrial damage.From the perspective of the concept of the five zang-organs deficiency of traditional Chinese medicine effects on learning and memory ability of body,and provide theoretical basis for it.Finally,SZJ provides experimental basis for the prevention and treatment of cognitive dysfunction.ObjectiveThe methods of molecular biology were used to observe the prevention and protection mechanism of the mitochondrial injury of rats in the mitochondria from the mitochondrial point of view.This paper discusses the correlation between visceral mitochondrial injury and brain mitochondrial injury in hypoxia,and the protection and prevention mechanism of SZJ.Qi deficiency of traditional Chinese medicine(TCM)from the perspective of the five zang-organs overall view on the human body the influence of learning and memory ability,and to provide the theoretical basis,provide the experimental basis for the clinical application of SZJ.Content and MethodsThe geriatric rats were grouped and except the normal group(group A),others were given anaerobic treatment in accordance with the experimental requirements.The Cl group(group B)and the SZJ intervention group(group C)were set up to establish hypoxia and mitochondrial injury.For eight weeks,the mice were tested for learning memory using the Morris water maze in the eighth week.By using enzyme-linked immunosorbent(ELISA)detection of rats and the related zang-fu organs within the mitochondria beta amyloid precursor protein(?APP),beta amyloid protein(AP1-42).The damage of mitochondrial DNA was detected by the use of the rat 8 hydroxydeoxyguanosine(8-ohdg).ResultsExperiment one.The comparison of rats to avoid latency.The results showed that the normal group was significantly different from the model group in the first day(P<0.01).There was a significant difference between normal and intervention groups(P<0.05).There was a significant difference between the model group and the intervention group(P<0.05).The next day,the normal group was significantly different from the model group(P<0.05).There was no significant difference between normal and intervention groups.The comparison between the model group and the intervention group was significantly different.On the third day,the normal group was significantly different from the model group(P<0.01).There was a significant difference between normal and intervention groups(P<0.05).The comparison between the model group and the intervention group was significantly different(P<0.01).On the fourth day,the normal group was significantly different from the model group(P<0.01).There was no significant difference between normal and intervention groups.The comparison between the model group and the intervention group was significantly different(P<0.01).The comparison of the total distance between the different groups of rats.Results showed that for the first day of the normal group and model group compared with the extremely significant difference(P<0.01),no obvious difference was found between normal group and intervention group comparison,model group and intervention group was extremely significant difference(P<0.01).The next day,the normal group and model group compared with the extremely significant difference(P<0.01),the intervention group and normal group have extremely significant difference(P<0.01),model group and intervention group was extremely significant difference(P<0.01).On the third day,normal group and model group compared with the extremely significant difference(P<0.01),the intervention group and normal group have extremely significant difference(P<0.01),model group and intervention group was extremely significant difference(P<0.01).The fourth day,the nonnal group and model group compared with the extremely significant difference(P<0.01),the intervention group and normal group with significant difference(P<0.05),model group and intervention group was extremely significant difference(P<0.01).Results show that space exploration in the original platform quadrant swimming time/total time,nonnal group compared with model group had extremely significant difference(P<0.01),the intervention group and normal group is no significant difference,model group and intervention group was extremely significant difference(P<0.01).Results showed that the number of space exploration through the target platform,nonnal group compared with model group had extremely significant difference(P<0.01),the intervention group and normal group is no significant difference,model group and intervention group was extremely significant difference(P<0.01).Experiment two.Results show that the continuous low pressure oxygen concentration APP content in brain tissue/brain tissue protein concentration,model group and normal group and SZJ between the intervention group were significant difference(P<0.05).Results show that the continuous low pressure oxygen building A ? 1-42 content in brain tissue concentration/brain tissue protein concentration,model group and normal group and SZJ between the intervention group were significant difference(P<0.05).Results show that the continuous low pressure made 8-OHdG content in brain tissue of oxygen concentration/brain tissue protein concentration,model group and normal group and the comparison between SZJ intervention group had obvious difference(P<0.01),comparing differences between SZJ intervention group and normal group significantly(P<0.05).Results show that the continuous low pressure made COX content in brain tissue of oxygen concentration/brain tissue protein concentration,model group and normal group there were significant differences(P<0.01),and there are obvious differences between SZJ intervention group(P<0.05),SZJ between intervention group and normal group was no significant difference.Experiment three.Sustained low pressure oxygen building eight weeks later,on analysis of mitochondrial DNA oxidative damage in renal tissue,significant difference between normal group and model group(P<0.05),no significant differences between the intervention group and normal group,model group and intervention group and the comparison between have obvious difference(P<0.05).Sustained low pressure oxygen,about COX content in the rat kidney tissue concentration/renal tissue protein level was compared,building eight weeks after the significant difference between normal group and model group(P<0.05),no significant difference between normal group and intervention group(P<0.05),the comparison between model group and intervention group had obvious difference(P<0.05).Continued low pressure oxygen,on mitochondrial DNA oxidative damage in rats with spleen tissue products 8-OHdG detection,comparison between normal group and model group was extremely significant difference(P<0.01),the intervention group and normal group have extremely significant difference(P<0.01),model group and intervention group had significant difference(P<0.05).Spleen tissues,the expression of the activity of COX normal group compared with model group had extremely significant difference(P<0.01),no obvious difference was found between normal group and intervention group comparison,model group and intervention group was extremely significant difference(P<0.01).According to the results of continuous low pressure oxygen,mitochondrial DNA oxidative damage in the rat heart tissue products 8-OHdG detection,between normal group and model group compared with significant difference(P<0.05),the intervention group and normal group is no significant difference,model group and intervention group had significant difference(P<0.05).On the expression of the activity of COX in heart tissue,there was no significant difference between normal group and model group,the intervention group and normal group was no significant difference,model group and intervention group was no significant difference.Continued low pressure oxygen,mitochondria in rat liver tissue,the expression of the activity of COX in normal group and model group was no significant difference,the normal group and intervention group was no significant difference,model group and intervention group was no significant difference.ConclusionsThe establishment of the CI model caused by oxygen-poor of the rat animal model was successful.SZJ can inhibit the APP,A?1-42 in rats of accumulation and DNA oxidative damage,protect brain mitochondria,in turn,play a role of nerve protection,further improve the influence of the lack of oxygen to the DI learning and memory ability,provide experimental support for the clinical application of SZJ.Oxygen increased stimulation of nerve cells to A ?,a large amount of the inflow Ca2+ overload,mitochondria swelling function disorder,cause mtDNA deletions or mutation,so the lack of oxygen to 8-OHdG yield increased,the oxidation damage product.SZJ has a protective effect on the mitochondria,and has certain protective effects on the oxidative damage and the activity of COX enzyme.The spatial ability of rats was improved compared to the model group.According to the standard deviation of the mean,the more 8-ohdg produced by oxygen,the greater the effect on the cognitive function of rats.Oxygen when related viscera mitochondrial injury and brain mitochondria damage have a certain correlation,basic shows the tendency of positive correlation.It provides the basis for the general view of the brain and the five-organ in traditional Chinese medicine(TCM).
Keywords/Search Tags:Shenzhi Jiannao Formula, cognitive impairment, Hypoxic, mitochondria, dementia, Learning memory
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