형질전환 생쥐를 이용한 Monocyte chemotactic protein-3의 동맥경화관련 기능에 관한 연구
Studies on the atherosclrotic function of monocyte chemotactic protein-3 using transgenic mice
iii, 63 p.
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Food intake, body weight, the levels of cholesterol and triglycerides in the plasma and activities enzymes involved in the lipid oxidation were monitored. In addition, the genes differentially expressed in response to the HFHC diet were also searched using the microarray analysis. Body weights of the transgenic mice fed normal diet were gradually increased during the entire experimental period up to 170%. However, it increased up to 120% and then decreased thereafter in the mice fed the HFHC diet, presumably due to the decreased in the food intake in the mice. In the level of plasma lipids, the mice fed HFHC diet showed a higher level of total cholesterol in the blood and lower in the triglyceride level. We have obtained a unique result in the level of HDL-cholesterol: it was surprisingly increased in the plasma of mice fed normal diet showing 72,6 in the HTR (HDL vs. total cholesterol ratio). Therefore, atherogenic index of the mice fed normal diet was drastically lower than in the wild-type mice. This result was supported through a marked increase in the expression of Apo-AI gene in the transgenic mice fed normal diet identified by microarray analysis. Activities of anti-oxidant enzymes were also increased in the transgenic mice fed HFHC diet, indicating that there might be more oxidative damages in the tissues of the mice fed HFHC diet leading to a progress toward the atherosclerosis. Supplementation of anti-oxidants to the diet, naringin and hesperidin, was shown to lower the level of the activities of anti-oxidant enzymes. In search of genes responding to the HFHC diet using the microarray analyses, numerous genes were found to be differentially expressed in response to the diet. Among those genes, the genes of interest were chosen as follows: 1) atherosclerosis-related, 2) PPARs-related, 3) lipoprotein receptor-related and 4) apolipoprotein-related genes. These genes were considered to be very important in relation to the function of MCP-3 and need to be thoroughly investigated in the future.