Study On Change Of The Neurovascular Unit In The Multiple Alzeimer’s Disease Rat Model

Objectives: To establish a multiple Alzheimer’s disease （AD） rat model andinvestigate the expression of neurovascular unit’s associated indicators: GFAP、NeuN、CD31and NOS1, observe the relationship between the neurovascular unit andneurodegenerative diseases.Based on this, the study could provide the the scientifictheoretical support for the prevention and treatment of AD.Methods:（1） Estabished a multiple Alzheimer’s disease rat model.Experimental groups: shamgroup and model group.model rats were injected D-galactose peritoneally followed withinjected Aβ1-42to lateral ventricle established model group, and sham group with normalsaline to placebo;（2） Behavioral ability test of learn and memory in rats through the Morris water mazeexperiment.（3） Biochemical indicators test for SOD, MDA, NO and NOS and its GSH/GSSGRatio in serum.（4） Morphological observation. Detect apoptosis using TUNEL, as well asdouble-label immunofluorescence assays and Western blotting to investigate the expressionof Trx in brain tissue.（5） Immunofluorescence assays to dectect the expression of GFAP, NeuN, CD31andNOS1in brain tissue.Results:（1） Morris water maze experiment showed that: compared with sham group, modelgroup rats’ escape latency was remarkably longer, and the ability of learn and memory in model group rats was significantly reduced. it was statistically significance（P <0.01）.（2） Biochemical tests showed that compared with sham group, the level of NO and theactivity of NOS in model group rats’ serum were significantly increased, and the activity ofSOD decreased significantly （P<0.01）, in addition, the content of MDA was significantlyincreased （P <0.01）.and GSH/GSSH ratio in model rats’ serum decreased significantly （P<0.01）.（3） Morphological observation. Apoptosis detection using TUNEL showed thatapoptosis exists in AD model rats, and Trx may reduce the expression of apoptosis in ADrat.（4） Double-label immunofluorescence assarys showed that: compared with shamgroup, the expression of GFAP in model group increased and the expression of NeuNdecreased while the expression of CD31increased. Expression of NOS1wasdown-regulated, which was primarily expressed in neurons.Conclusion:（1） A multiple AD rat model was successfully established by injected D-galactoseperitoneally combined with injected Aβ_1-42to lateral ventricle. The behavioral, biochemicalindicators of the multiple AD model shows that model rats’ learn and memory ability aredecreased,and free radical scavenging capacity are decreased too.Therefore, this AD modelcan be used in the basic research of Alzheimer’s disease.（2） Compared with sham group, the expression of Trx in model group rat brain tissuedecreased, indicating that an important association between Trx and apoptosis. Trx has arole in inhibition of apoptosis, and may be used as a target in AD prevention and treatment.（3） In model group rats, Aβ increased or accumulation, astrocys cells and vascularendothelial cells in the neurovascular unit activitied，while neuron occurred apoptosis ordeath. Those may cause blood-brain barrier and affect the steady of the NVU.So theneurovascular unit maybe an entry point. Protecting the neurovascular unit may conduct toearly prevention and treatment of neurodegenerative diseases, congnitive dysfunction andits pathological mechanism.