動脈硬化の発症要因に関する研究 : 特に組織低酸素時における過酸化脂質生成の意義について
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概要
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The present studies were undertaken to investigate the atherogenic effects of tissue hypoxia. In the in vivo experiment, 10 cholesterol-fed rabbits were exposed to 10% oxygen (hypoxic) or 40% oxygen (hyperoxic) for 5 hours daily on 5 days of each week through 16 weeks, and the changes in serum lipid levels were observed biweekly. In the in vitro experiment, it was observed whether lipoperoxide (LPO) was produced in cultured smooth muscle cells (SMCs) of normal rabbit's aorta for 48 hours under each condition with 2% oxygen (hypoxic) or 20% oxygen (normoxic). The results were as follows : 1) LPO levels in the serum revealed a gradual increase in both hypoxic and hyperoxic groups, but its degree in hypoxic group was higher than that in hyperoxic group. 2) LPO levels in cultured SMCs were higher under hypoxic condition than those under normoxic condition, but no difference was found in LPO levels in culture medium between both conditions. 3) Without the addition of serum to culture medium, LPO levels in SMCs were still higher under hypoxic condition than those under normoxic condition, indicating the production of LPO in the cell itself. 4) The increase of LPO levels in SMCs under hypoxic condition was inhibited by the addition of 10-100 μM α-tocopherol to the culture medium. From these results, it is postulated that an increase in LPO production in aortic wall is induced by tissue hypoxia and accordingly accelerates the atherogenic process.
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