| 1. BackgroungDementia is a complex disease which be characterized by impairments in cognition and behavior. Behavioural and psychological symptoms of dementia are present in the course of the illness in most patients with dementia. The incidence of dementia among the elderly population is rising rapidly around the world. Due to the numerous cases of patients, there are more and more burden of society, economy and family. Alzheimer's disease(AD) is the leading type of dementia. AD is a neurodegenerative disorder of the aged that has multiple factors, which contribute to AD's etiology in terms of initiation and progression. There are several hypotheses have been formulated to explain this debilitating disease, and those hypotheses often have overlapping features. The best-known hypothesis to explain AD is the Amyloid Cascade Hypothesis which involves the role of the accumulation of amyloid-βpeptide(Aβ) in the brain. Other theories include Dysfunction of Neurovascular Unit which suggests manifold neurovascular pathogenic cascades for AD, cholinergic hypothesis, the role of oxidative stress or neuroinflammation, genes mutation and so on. Current therapeutics on the market, including cholinesterase inhibitors, N-methyl-D-aspartate receptor antagonists and productions of modulating Aβmetabolism, provide symptomatic relief but do not alter progression of this disease. Therefore, progress in the areas of prevention and disease modification may be important. Based on Traditongal Chinese medicine, dysfunction of brain, kidney, heart, spleen and liver all may due to AD.Deficiency of kidney essence, asthenia of qi and blood, sputum and blood stasis, internal injury due to seven emotions, prolonged illness consuming healthy qi all would impair the brain. The basic therapeutic methods is Invigorating kidney and supplementing essence, relieve accumulation and resolve stagnation. Traditongal Chinese medical prescriptions are multifunctioning that could theoretically intervene at any of a number of sites to abate the changes associated with the development of AD and have a better effection.This experiment is guided by the pathogenesis theories of Consuming of Kidney Essence and Toxin Hurts Brain Collaterals to study SAMP8(model-P) & hippocampus injection of Aβ1-40 in SAMR1(model-A) models, to compare the actions of Liu Wei Dihuang granule(LWDH) and Tong Luo Jiunao dripping pill(TLJN), and to find the feature of those prescriptions. 2. Objective1) To test the correlation of aging and cognition impairments in two models;2) To compare the effect of behavioral test and morphology of two models;3) To compare the speacil function of two prescriptions, and ascertain the potential drug targets.3. Methods1) To investigate the diversity of 2-month-old,6 month-old and 8 month-old SAMP8 and SAMR1 mice using Morris water maze and passive avoidance test(Step-up test).2) To investigate the discrepancy of 8 month-old model-P and model-A treated by LWDH(PL group & AL group) and TLJN(PT group & AT group) using Morris water maze and passive avoidance test(Step-through test).3) To compare the difference in all group on expression of Aβ,APP, BACE1, IDE, LRP1, RAGE, apoE and a2M using immunohistochemistry.4) To compare the difference in all group on level of APP, BACE1, IDE, LRP1, RAGE, apoE and a2M using Weatern blotting.4. Results1) To compare with the N group, there are diversity in MWM escape latency, success rate and Step-up test latency, wrong frequency, and Step-though test latency, wrong frequency of 8-month-old model-P and model-A. To compare with the N group, there are diversity in both Step-up test and Step-though test wrong time of model-A. To compare with the N group, there are diversity in MWM swimming speed of model-P.2) To compare with the A group, there are difference between model-A and model-P on MWM swimming speed, Step-up test wrong frequency, Step-though test wrong frequency, wrong time and expression of APP(cortex), BACE1(cortex), IDE(cortex and hippocampal), LRP1(hippocampal),RAGE(cortex and hippocampal) and apoE(cortex).3) The irregular expression of Aβ, APP, BACE1, IDE, LRP1, RAGE, apoE and a2M in brains of model-P and model-A. The regulated expression of APP, BACE1, IDE, LRP1 RAGE and apoE were shown in AT group as well as the regulated expression of Aβ, APP, BACE1, IDE, LRP1, RAGE, and a2M were tested in PL group. TLJN have function on model-A by regulated Step-though test latency and expression of APP, BACE1, IDE, LRP1,RAGE and apoE. LWDH have function on model-P by regulated MWM success rate, Step-though test latency and expression of Aβ,APP, BACE1, IDE and RAGE.5. Conclusions1) There are correlation of aging and cognition impairments in two models;2) Model-P and model-A have severely impaired acquisition and retention of spatial learning task and passive avoidance response, and neurochemical. So SAMP8 maybe a more severely model.3) These two traditongal Chinese medical prescriptions have significant effection, due to selecting of treatment based on the differential diagnosis. The expreesion of APP,BACE1,IDE coule be useful develop and evaluate potential new formulations.4) There are few difference between LWDH and TLJN in clearance of Aβby LRP1 system. So the evaluation for traditongal Chinese medical prescriptions should be unambiguous.5) The behavioral test maybe unsuitable as a evaluation for different traditongal Chinese medical prescriptionsIn conclusion, SAMP8 and hippocampus injection of Aβ1-40 in SAMR1 mice have difference on MWM swimming speed, Step-up test wrong frequency, Step-though test wrong frequency, wrong time and expression of APP, BACE1, IDE, LRP1,RAGE and apoE. To hippocampus injection of Aβ1-40 in SAMR1 mice, TLJN have function by regulated Step-though test latency, and expression of APP, BACE1, IDE, LRP1,RAGE and apoE. On the other hand, to SAMP8 mice LWDH have function by regulated MWM success rate, Step-though test latency and expression of Aβ, APP, BACE1, IDE and RAGE. These two models and two traditongal Chinese medical prescriptions have their own characteristics. |
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