| Objective:With coming of aged society in the world. senile disease has become a important topic that can't be ignored. According to an epidemiological investigation of the foreign country, The senile dementia including Alzheimer's disease, has become the fourth cause of death, following heart and Cerebral vessels disease,tumor and so on. It was belived that the increase in generation and deposition of β-amyloid peptide (Aβ) is one of the pivotal factors in forming neurofibrillary tangles, which induce degeneration of neuron. Aβ affects the happening and development of AD.There are multiple factors to affect formation of Aβ. High cholesterol is a risk factor for AD. In vivo and in vitro experiment all suggested that the inhibiting synthesis of cholesterol, lowering the level of serum cholesterol or cell membrane cholesterol can reduce generation of Aβ and decrease incidence of AD. So far, all studys are about the relationships between inhibiting synthesis of cholesterol and generation of Aβ. Cholesterol is important component of membrane and myelin,which can modulate the permeability and fluidity of membrane and the transport of substance. However, inhibiting synthesis of cholesterol will cause some side-effects. It is a homeostasis between synthesis and catabolism of cholesterol. The cholesterol in brain is synthesized de novo in situ . HMG-CoA reductase is a limiting-speed enzyme in the course of synthesis of cholesterol. In addtion, brain cholesterol can be converted by cholesterol 24S-hydroxylase (CYP46) to 24S-hydroxycholesterol which can across blood brain barrier easily. In turn the 24S-hydroxycholesterol is converted to bile acid in liver. Finally the bile acid will be transported to outside of body from liver. Converting cholesterol to bile acid is a important way for body to eliminate cholesterol. The synthesis of bile acid begains with the converting cholesterol to 7-α hydroxycholesterol by 7-α hydroxylase in microsome and ends with the formimg of 24-C primary bile acid by ?-oxidation in peroxisome. It is unclear whether the level of Aβ can be reduced by conversion of cholesterol to bile acid. We all know cholestyramine is a drug used to lower serum cholesterol levels through its ability to bind intestinal bile acids and promote their excretion and synthesization. It is also known that Diethylhexyl phthalate (DEHP) can proliferate proxisome by actived PPAR-α, promote the synthesis and excretion of bile acid and reduce serum total cholesterol. So we treated rats with DEHP and cholestyramine to see if the level of cholesterol and brain Aβ can be changed by increaseing in bile acid synthesis or not.It will provid a new solution and target point to cure AD if it dose work. Methods1 Animal groupsUsing sixty male Wistar rats aged six months as experimental animal. We divided these animals into two groups at random. One group contains 45 rats fed with high cholesterol diet, the another group contains 15 rats fed with basal diet. After 4 weeks, these rats fed with high cholesterol diet are led to hypercholesterolemia, then we divided these 45 rats into 4 groups: ①High cholesterol diet group(HCD): fed with High cholesterol diet; ②cholestyramine diet group(CD): fed with 1% cholestyramine diet; ③DEHP diet group(DD): fed with 2% DEHP diet; ④Change to basal diet group(CBD): Change to basal diet. ⑤Basal diet(BD): 15 rats fed with basal diet from beginning to end as control group.continue 9 weeks, amount to 13 weeks. Then we determined its ability of learning and memory, and collect blood and brain tissues ready for determination of serum cholesterol, serum bile acid, brain Aβ, brain cholesterol and extraction of gross mRNA of brain.2 Data determining and methods①To determine the ability learning and memory of rats with step down test method. ②Using type Olympus Au2700 automatic biochemistry analyzer, determining serum cholesterol, serum bile acid;③Brain cholesterol were extracted with chloroform/methanol (2:1), dried and resuspended with water, then determinated it...
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