The Research Of NaoLiJian’s Metabolomics Basing On Aβ’s Neurotoxicity

Alzheimer’s disease(AD) is a degenerative diseases of the nervous system which is unknown reason, it’s main pathological changes consist of the extensive nerve cells apoptosis, SP depositing, NFT and the nerve cells reducing. TCM compound NaoLiJian is protocoled according to the AD’s pathogenesis of "ShenXuDuSun", and it has the effect of "BuShenJianNao, JieDuYiZhi". A β’s neurotoxicity is a important factor in the happening and developing process of AD, and is also a hot target in the research of TCM resisting to AD in recent years. Metabolomics is one of the effective ways to evaluate the overall effect of TCM compound. This research has mainly studied that NaoLiJian how to influence the AD rats’s learning and memory capacity, hippocampus morphology, hippocampus neurotoxicity and metabonomics, etc.Objetive:To explore NaoLiJian’s relieving function to Aβ’s neurotoxicity and it’s mechanism, to reveals preliminarily the internal material and metabolic pathways change in the AD rats’body and NaoLiJian’s intervention to the metabolic pathways.Methods:Using the agglomerate state of Aβ25-35to establish AD model by injecting in the rats’bilateral hippocampal. After drug intervening, using the Morris water maze to observe NaoLiJian’s influence on the learning and memory capacity of AD rats, using pathological ways to watch it’s influence on the brain morphology, using immunohistochemistry method to test IDE, cdk5, GSK-3, SYN expression and their average optical density in the hippocampal. Collecting metabolic product, after the steps of sample processing, testing, data processing, then to observe it’s influence on the metabonomics.Results:1. Effects on function of learning and memory of AD ratsPlace navigation show that the escape latency of the model group are significantly extended, and the latency of the drug groups are significantly shorter than the model group (P<0.05). Spatial probe test show that the stating in the first quadrant time and platform retention time of the model group shorten significantly, and the number of passing platform reduce remarkably; while the time of the drug groups spending are longer and the number are more than the model group (P<0.05)2. Effects on brain pathology morphologyThe results show that the most cases of the model group have appeared to nerve cells reduce in different degree, neuronal apoptosis and gliocytes hyperplasia, but the situation of the drug groups are significantly better than the model group.3. Effects on IDE expressionThe results show that the products of IDE positive immune response are strikingly low expression in the model control group, while the expression of NaoLiJian each dose groups are elevatory, medium dose group are obviously higher than the model group. The IDE average optic density of the model group are significantly lower than the blank control group (P<0.01), while its in treatment groups are significantly increased (P<0.05).4. Effects on CDK5expressionThe results show that the cdk5expression of the model group are obviously higher than the sham operation group, while NaoLiJian each dose groups are significantly lower than the model group. The cdk5average optic density in hippocampus of the model group are remarkably higher than the blank control group (P<0.01), while its in NaoLiJian each dose groups are significantly lower than the model group (P<0.05).5. Effects on GSK-3expressionThe results show that the products of GSK-3positive response can be seen in hippocampus CA1area after A β injecting, the GSK-3expression of the model group are strikingly more than the blank control group, while the expression both of NaoLiJian each dose groups and the sham operation group are significantly reduced. The average optic density of the model control group are obviously higher than the blank control group (P<0.01) this suggests that the GSK-3activity of the model group markedly enhanced; while its in NaoLiJian each dose groups are significantly reduced (P<0.01), but no significant differences between groups (P>0.05)6. Effects on SYN expressionThe results show that the SYN expression of the model group are remarkably lower than the sham operation group(P<0.05); while the all SYN expression of NaoLiJian groups are obviously higher than the model group (P<0.01). The average optic density of the model group are significantly lower than the sham operation group (P<0.01), while the all average optic density of NaoLiJian groups are markedly higher than the model group (P<0.05)7. Effects on metabonomicsThe results show that the mitochondria and biological membrane of AD rats have appeared significant change after establishing model, the content of corresponding metabolic markers in the urine have changed also. The positive drug group have certain callback function, but the callback ability of NaoLiJian groups are poor overall, total have certain curative effect merely.Conclusion:1. NaoLiJian has effect on improving AD rats’the capacity of learning and memory, this suggests that NaoLiJian can increase intelligence. 2. Aβcan induce brain pathology morphological change, while NaoLiJian has protective function on it.3. NaoLijian has effect on enhancing IDE activity.4. NaoLiJian has good suppressive effect on cdk5and GSK-3high expression of AD model, this prompt that it can inhibit and/or antagonize excessive or abnormal tau protein phosphorylation which can form neurons fiber tangles; NaoLiJian can improve the low expression level of SYN in the hippocampus, this prompt that it has the function on stimulating nerve synapsis remodeling.5. The process of AD’s damage include abnormal energy metabolism and lipid membrane structure, NaoLiJian’s callback ability overall to these is poor, but it has certain curative effect.