刘秀凤,郑友祥（阜宁县中医院，江苏阜宁224400）
20世纪70年代末，药物专家根据人体胆固醇生物合成的机制，开始筛选胆固醇合成限速酶——3羟3甲基戊二酸单酰辅酶A（hydroxymethylglutaryl coenzyme A reductaseinhibitor，HMG—CoA...刘秀凤,郑友祥（阜宁县中医院，江苏阜宁224400）
20世纪70年代末，药物专家根据人体胆固醇生物合成的机制，开始筛选胆固醇合成限速酶——3羟3甲基戊二酸单酰辅酶A（hydroxymethylglutaryl coenzyme A reductaseinhibitor，HMG—CoA）还原酶抑制剂。经过十多年的努力，1987年，第一个他汀品种上市并获美国国家食品药品监督管理局（Foodand Drug Administration，FDA）批准。展开更多
核受体的研究近几年已有飞速的发展。LXRa(Liver X Receptor a)是一种与脂类代谢有关的核受体。研究发现LXRa的靶基因具有调节脂类的吸收、运输、转化和生物合成的功能,此外,LXRa在糖类的代谢等方面也有重要的调控作用。研究结果表明LXR...核受体的研究近几年已有飞速的发展。LXRa(Liver X Receptor a)是一种与脂类代谢有关的核受体。研究发现LXRa的靶基因具有调节脂类的吸收、运输、转化和生物合成的功能,此外,LXRa在糖类的代谢等方面也有重要的调控作用。研究结果表明LXRa与动脉粥样硬化的发生有非常密切的关系。目前利用LXRa为靶标进行抗动脉粥样硬化药物筛选已经成为一个重要的研究方法。展开更多
The anti atherosclerotic effect of fluvastatin at doses insufficient to lower serum cholesterol on the catheter induced intimal thickening and possible mechanism were investigated in abdominal aorta of rabbits. Method...The anti atherosclerotic effect of fluvastatin at doses insufficient to lower serum cholesterol on the catheter induced intimal thickening and possible mechanism were investigated in abdominal aorta of rabbits. Methods.Fifty six rabbits were randomly divided into eight groups(n=7,each).Fluvastatin was given mixed with food at daily dose of8mg/kg starting 5 days before catheterization.Light microscope,immunohistochemistry,transmission electron microscope and RT PCR assay were applied to assess vascular smooth muscle cell (VSMC)proliferation and apoptosis, as well as oncogene expression in vascular wall. Results.At day 10 and day 15 after catheter induced denudation intima/media(I/M)thickness ratio was obviously higher, and also the percentage of PCNA positive cells and TUNEL positive cells in media was significantly higher compared with controls.The intimal hyperplasia was mostly composed of α SM actin positive cells.In rabbits given fluvastatin I/M ratio and the percentage of these positive cells significantly decreased compared with those without fluvastatin.The overexpression of proto oncogene H ras mRNA and decreased expression of anti oncogene p53 mRNA were found after vascular injury,whereas fluvastatin significantly reduced H ras mRNA and increased p53 mRNA expression. Conclusion.Proliferation of VSMC in the media and the migration to the intima can be inhibited,and apoptosis of VSMC be induced by short term use of fluvastatin after balloon catheter denudation,independent of serum lipid change.The underlying mechanism is presumably associated with the influence of fluvastatin on oncogene expression in the injured vascular wall.展开更多
文摘刘秀凤,郑友祥（阜宁县中医院，江苏阜宁224400）
20世纪70年代末，药物专家根据人体胆固醇生物合成的机制，开始筛选胆固醇合成限速酶——3羟3甲基戊二酸单酰辅酶A（hydroxymethylglutaryl coenzyme A reductaseinhibitor，HMG—CoA）还原酶抑制剂。经过十多年的努力，1987年，第一个他汀品种上市并获美国国家食品药品监督管理局（Foodand Drug Administration，FDA）批准。
文摘核受体的研究近几年已有飞速的发展。LXRa(Liver X Receptor a)是一种与脂类代谢有关的核受体。研究发现LXRa的靶基因具有调节脂类的吸收、运输、转化和生物合成的功能,此外,LXRa在糖类的代谢等方面也有重要的调控作用。研究结果表明LXRa与动脉粥样硬化的发生有非常密切的关系。目前利用LXRa为靶标进行抗动脉粥样硬化药物筛选已经成为一个重要的研究方法。
文摘The anti atherosclerotic effect of fluvastatin at doses insufficient to lower serum cholesterol on the catheter induced intimal thickening and possible mechanism were investigated in abdominal aorta of rabbits. Methods.Fifty six rabbits were randomly divided into eight groups(n=7,each).Fluvastatin was given mixed with food at daily dose of8mg/kg starting 5 days before catheterization.Light microscope,immunohistochemistry,transmission electron microscope and RT PCR assay were applied to assess vascular smooth muscle cell (VSMC)proliferation and apoptosis, as well as oncogene expression in vascular wall. Results.At day 10 and day 15 after catheter induced denudation intima/media(I/M)thickness ratio was obviously higher, and also the percentage of PCNA positive cells and TUNEL positive cells in media was significantly higher compared with controls.The intimal hyperplasia was mostly composed of α SM actin positive cells.In rabbits given fluvastatin I/M ratio and the percentage of these positive cells significantly decreased compared with those without fluvastatin.The overexpression of proto oncogene H ras mRNA and decreased expression of anti oncogene p53 mRNA were found after vascular injury,whereas fluvastatin significantly reduced H ras mRNA and increased p53 mRNA expression. Conclusion.Proliferation of VSMC in the media and the migration to the intima can be inhibited,and apoptosis of VSMC be induced by short term use of fluvastatin after balloon catheter denudation,independent of serum lipid change.The underlying mechanism is presumably associated with the influence of fluvastatin on oncogene expression in the injured vascular wall.
