Study On Effect Inducing Atherosclerosis Of The Testing Rat With Copper Intake

BackgroundCopper exist in the soil and water, and is rich in the marine and terrestrial animals and plants. Copper is used widely in all walks of life. The copper compounds are important chemical substances for sterilization and disinfection. The utilization of copper increase following The development of science and technology, and various factors can increase human environmental copper exposure such as more copper smoke and copper dust generated in environment, more copper be used in pesticides and disinfections, copper compounds be used in medicine, and so on. As we all know, copper is an important component of many enzyme, and abnormal copper level of the body might lead to dyslipidemia, lipid metabolism disorder, the degree of lipid peroxidation changes and endothelial dysfunction, and so on, and all of these factors might caused the occurrence and development of atherosclerosis (AS) directly or indirectly.The risk assessment (RA) of the potential chemical in environment is a important part of protecting environment and human health, and as a important metal existed in the production and living environment of people and a necessary trace elements in human body, copper should be carry out the evaluation of health effects based on the theory of risk assessment of chemical substances in environment. So, it is a important part in the risk assessment of copper in environment to research the risk of copper might caused occurrence and development of AS.At present, amount of researchs were only focused on the case-control studies and descriptive materials, and most of them studied the copper level after the diseases occurred, while it is limited to provide the basis of the copper between the pathogenesis of AS; and many of the epidemiological data and the studies about the effect of copper on AS are in the qualitative phase, can only to identified the hazards of copper leading to AS, and lack of the systems and quantitative results to provide a scientific data materials for the dose-response relationship evaluation and the key effect evaluation of AS induced by copper. Obtain the relevant data through animal experiments is a important way of dose-response data collection and selection in the risk assessment, also an important basis for the research of human dose-response relationship.ObjectRats as the subject in the study, research the effects of copper intake on AS quantitatively from animal level. Find out a sensitive evaluating indicator to the copper intake in rat. Study the relationship between the relevant factors the every links of AS occurrence and development with copper intake level starting from the clinical indicators of lipid and get involved in different links including lipid peroxidation, lipoprotein metabolism and vascular endothelial damage, determine the security scope of copper intake would not lead to AS and provide the data base for the dose-response relationship of the risk assessment of copper.MethodThe rat was used to carry out animal experiments in this study, the copper intake of rats were controlled by feeding the rats on copper deficiency feeds and given different doses of copper gluconate. After the rats were treated for 90 days, dissect the experiment rats and got the blood, liver , carotid and femoral artery, determined the related indicators of AS of blood and made the biopsy of carotid and femoral artery observing whether appeared the AS symptoms. Analyzed the correlation between the copper level in rat body with the related indicators of AS, using the ceruloplasmin( CP) as a indicator to evaluate the copper intake in rat. Determine the scope of CP that would not lead to AS by benchmark dose (BMD) to evaluate the important risk factor ox-LDL and the sensitive predict indicator of AS. Result1. Rat serum ceruloplasmin (CP) level show logarthmic correlation with the copper intake (y=5.192ln(x)+30.276, R~2=0.9845, p<0.05) .2. When the CP activity level is lower than 15.912U/L in rat serum, the factors associated with vascular endothelial cell injury would be promoted, and the levels of lipid peroxidation enhanced, the TG and LDL in serum increased and the HDL lower, and the danger of leading AS is strong.3. When the CP activity level is higher than 44.022U/L in rat serum, the ox-LDL generation increased, and the initial link of AS in rat start, resulting the vascular endothelial cell injury, it could cause the formation of AS, and HCY, CRP might make a strong warning to the AS at this time.4. When the CP activity level in the scope of 37.569-44.022U/L AS would not be formed; while as a result of an increase in ox-LDL, may be aggravated the degree of AS in the AS rats. And the TG level in rat serum increased when the CP activity level in the scope of 15.912-20.442U/L.5. No adverse changes in the indicators of AS be found when the CP activity level in scope of 20.442-37.569U/L.6. Ox-LDL and HCY to be as the observe end of AS and using the benchmark (BMD) to calculate, the CP activity remain at 25.2259-30.2523U/L is the safe scope that could not lead to AS.Conclusion1. Rat serum ceruloplasmin (CP) activity and copper intake showed significant correlation, and the CP is a sensitive indicator to evaluate the copper intake of rat;2. In the case of the research design, no adverse changes in the indicators of AS be found when the copper intake in rats in the 0.175-4.015mg/kg.bw, and the CP activity level of rats in scope of 20.442-37.569U/L.3. Ox-LDL and HCY to be as the observe end of AS and using the benchmark (BMD) to calculate, the CP activity remain at 25.2259-30.2523U/L is the safe scope that could not lead to AS.4. Homocysteine (HCY) could make early warning when the relevant factors become active, HCY is a more sensitive indicator for directing the danger of AS;...