Szolkiewicz M, Sucajtys E, Chmielewski M, Wolyniec W, Rutkowski P, Boguslawski W, Swierczynski J, Rutkowski B
Department of Nephrology, Medical University of Gdansk, ul.Debinki 7, 80-211 Gdansk-Wrzeszcz, Poland.
Horm Metab Res. 2002 May;34(5):234-7. doi: 10.1055/s-2002-32135.
Hypercholesterolemia plays an important role in the lipid abnormalities in chronic renal failure (CRF). It is thought to contribute to both a progression of renal failure and atherosclerosis. Despite intensive research, the etiopathogenesis of hypercholesterolemia in CRF patients is still obscure. The present study was designed to evaluate the possible role of cholesterol overproduction in the development of hypercholesterolemia associated with experimental CRF. We found that plasma total cholesterol and cholesterol distributed in VLDL, LDL and HDL concentrations were significantly enhanced in CRF rats. Simultaneously, the rate of liver cholesterol biosynthesis in vivo (measured by determining the incorporation of tritium from tritiated water intraperitoneally injected into cholesterol ), liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and liver HMG-CoA reductase mRNA presence were elevated. Significant increases in activity of liver malic enzyme, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, NADPH-producing enzyme (required for cholesterol synthesis) have also been observed in CRF rats. In conclusion, the increased rate of liver cholesterol biosynthesis due to increase of HMG-CoA reductase and NADPH-producing enzyme gene expression could be one of the possible causes of hypercholesterolemia in CRF animals.
高胆固醇血症在慢性肾衰竭（CRF）的脂质异常中起重要作用。它被认为与肾衰竭进展和动脉粥样硬化均有关。尽管进行了深入研究，但CRF患者高胆固醇血症的病因发病机制仍不清楚。本研究旨在评估胆固醇过度生成在实验性CRF相关高胆固醇血症发生中的可能作用。我们发现CRF大鼠血浆总胆固醇以及分布于极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）中的胆固醇浓度显著升高。同时，体内肝脏胆固醇生物合成速率（通过测定腹腔注射的氚化水中的氚掺入胆固醇的情况来衡量）、肝脏微粒体3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶活性以及肝脏HMG-CoA还原酶mRNA表达均升高。在CRF大鼠中还观察到肝脏苹果酸酶、葡萄糖6-磷酸脱氢酶和6-磷酸葡萄糖酸脱氢酶（胆固醇合成所需的产NADPH酶）的活性显著增加。总之，由于HMG-CoA还原酶和产NADPH酶基因表达增加导致肝脏胆固醇生物合成速率加快可能是CRF动物高胆固醇血症的可能原因之一。
