| Alzheimer’s disease(AD) is a kind of primary central nervous systemdegenerative disease of unknown etiolory. It often starts in elderly orpresenium, slow onset, progress gradually, main performance for dementia.The mobility mechanism of AD is not clear so far.More and more evidencehave shown that brain of AD patients were deposited a lot of solubilitybeta-amyloid (beta amyloid, Aβ), it can induce oxidative stress by damagemitochondrial structure and function. So the oxidative stress mediated by Aβis important for the progress of AD neuron degeneration.Senescence-accelerated mouse prone8is a model for the study of aging andanti-aging, and it has a lot of typical behaviour and pathology feature of AD,such as cognition impairment, memory deterioration, Aβ deposited inhippocampus and cortex, neurofibrillary tangle and mitochondrial dynamicschang. SAMP8is known as a better ideal model for sporadic AD.Oxidative stress can damage tissue and cell by induce lipid peroxidationreaction.4-hydroxynonenal (4-HNE) is the most representative lipidperoxidation product. However, the study between oxidative stress andanti-inflammatory cytokine were less and the conclusion were inconformity.Peroxidase proliferation receptors gamma is sensitive for oxidative stress, itcan decrease radical and protect cardiovascular, but the mechanism for AD isnot clear.Mitochondria is always as a important organelle for evaluate theoxidative stress level, it is the main place that product and clear the reactiveoxygen species, and the main target organ that damage by ROS. Mitochondrialfunction is determined by its morphology, and the morphology is regulated bythe fission and fusion protein. Fis1is a important mitochondrial associated fission protein in these protein, which is important for mitochondrial structure.SS31peptide is a new type mitochondrial targeting peptide. It canpermeate cytomembrane, which has the capacity that specific binding themitochondrial intima, stabling mitochondrial intima, eliminating andpreventing the ROS of intracellular. SS31can relieve the reurovirulenceproduced by Aβ in brain of AD patients.Objective: This study through immunohistochemical method to observethe4-HNE expression in the hippocampus of SAMP8mouse; through Westernblot method to observe the Fis1and PPAR-γ expression in the hippocampus ofSAMP8mouse; through transmission electron microscopy observe themitochondrial ultrastucture changes. At the same time we observe the effect ofSS31on SAMP8mouse’s learning and memory ability, in order to explore theimpact of oxidative stress and mitochondrial structure changes on ADmorbility and provide new ideal for the treatment of AD.Methods: We buy the SAMP8mouse and SAMR1mouse from theanimal centre of First Hospital Affiliated to Tianjin University of TCM, whichare clean animal and fed in clinical research center housed separately of HebeiProvince People’s Hospital. The mouse were fed by the feeder of the animalcentre, which are fed with standard mouse grain and clean water. We choosethe8month-old mouse to divide into groups. We choose30mouse of8month-old SAMP8and10mouse of8month-old SAMR1. The mousedivided into groups: the SAMP8mouse divided as:10SAMP8mouse thatwere pretreated with5mg SS31peptide group as the medicationadministration group,10SAMP8mouse that were pretreated with normalsaline as the solvent group(NS group),10SAMP8mouse as the model group,10SAMR1mouse as the control group. After8week-continuous-injection, allof the mouse were respectively investigated by Morris water maze test.(placein the forensic medicine teaching and research section of Hebei MedicalUniversity). We took the brain of all the mouse to test the following subjects:use electron microscope to test the mitochondrial form of different groupsmouse’ hippocampus, use immunohistochemical to test the4-HNE and Nissl’s staining to test the content of nissl bodies of different groups mouse’hippocampus and use Western blot to test the expression of ppar-γ and fis1of different groups mouse’ hippocampus.Results:1The influence of S331peptide to SAMP8mouse’ behaviour: Afterrespectively injected for8weeks, the Morris water maze test show that:(1)escape latency:by comparison to the SAMR1group, the escape latency ofSAMP8group was significantly lengthened(P<0.01), by comparison to theSAMP8-V group, the escape latency of SS31group was significantlyreduced(P<0.05), the difference between SAMP8group and SAMP8-V groupwas not obvious.2The influence of SS31peptide to SAMP8mouse’ hippocampus’ cellmorphology: After respectively injected for8weeks, the electron microscopeshow the mitochondrial form of the mouse’ hippocampus: mitochondrialmorphology: by comparison to the SAMR1group and the SS31group, themitochondrial morphology in hippocampus of SAMP8-V group was obviouslysmall, swell, and the ridge of the mitochondria was diminished and becomebroken bits. The Nissl’s staining show that: by comparison to the SAMR1group, the number of nissl bodies in SAMP8mouse’ hippocampus wereobviously decreased(P<0.01), by comparison to the SAMP8-V group, the nisslbodies of SS31group was significantly increased(P<0.05), the differencebetween SAMP8group and SAMP8-V group was not obvious.3The influence of S331peptide to the ROS content of SAMP8mouse’hippocampus: tested the4-HNE content of different group of the mouse’hippocampus after the intervene, show that: by comparison to the SAMR1group the content of4-HNE in SAMP8group of hippocampus was obviouslyhigh, by comparison to the SAMP8-V group, the content of4-HNE in SS31group of hippocampus was obviously decreased, the difference betweenSAMP8group and SAMP8-V group was not obvious.4. The influence of S331peptide to SAMP8mouse’ hippocampus that theexpression of Fis1and PPAR-γ: After respectively injecting for8weeks: by comparison to the SAMR1group, the expression of Fis1in SAMP8mouse’hippocampus was obviously high(P<0.01), by comparison to the SAMP8-Vgroup, the expression of Fis1in SS31group in hippocampus was obviouslyreduced(P<0.05), the difference between SAMP8group and SAMP8-V groupwas not obvious. by comparison to the SAMR1group, the expression ofPPAR-γ in SAMP8mouse’ hippocampus was obviously high(P<0.01), bycomparison to the SAMP8-V group, the expression of PPAR-γ in SS31group and SAMP8-V group of hippocampus was not obvious (P>0.05).Conclusion: SAMP8mouse’ hippocampal neuron exist peroxidation,increased mitochondrial fission and structure changing. SS31peptide maydecrease the product of4-HNE by antioxidation, and down-regulated Fis1.Thereby improve mitochondrial function and pathologic changes. Improve ADmodel mouse’ learning and memory function ultimately. |
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