Research on the pathogenis and protection of Atherosclerosis

1.动脉粥样硬化发病机制的研究：血管平滑肌细胞(VSMC)的增殖和脂质沉积在动脉粥样硬化的发病机制中起重要作用。1)大鼠主动脉血管平滑肌细胞含有1，25-二羟基维生素D_3的特异性受体，促进细胞增殖，抑制糖胺聚糖的合成。2)血小板衍生生长因子(PDGF)增加兔软骨细胞内钙离子浓度([Ca^&lt；2+&gt；]i)，刺激DNA和糖胺聚糖的合成。PDGF的拮抗剂苏拉明可抑制[Ca^&lt；2+&gt；]i的升高和DNA的合成。3)低密度脂蛋白使[Ca^&lt；2+&gt；]i升高。低密度脂蛋白通过产生三磷酸肌醇(IP_3)引起细胞内[Ca^&lt；2+&gt；]i的释放。研究不同化合物对细胞内钙信号系统的影响1)前列腺素F2和血管紧张素II(AII)是一种强的血管收缩物质，可使VSMC内[钙离子]i升高，引起细胞内钙离子释放。血管扩张剂尼可地尔可抑制前列腺素F_2和前列腺素A_2引起的细胞内[Ca~(2+)]i的升高。2)钾离子载体伐林霉素可抑制AII诱导的细胞内钙离子释放，但不能抑制离子载体离子霉素诱导的钙离子释放。3)硝酸甘油和尼可地尔对猪冠脉平滑肌细胞膜上钙离子通道阻滞剂钙通道阻滞剂的作用不明显。

1. Research on the Pathogenesis of Atherosclerosis: Proliferation of vascular smooth muscle cells (VSMC) and deposition of lipid is important for the pathogenesis of atherosclerosis.1) Vascular smooth muscle cells from rat aorta contaied a specific receptor for the 1,25-dihydroxyvitamin D_3 and it stimulated the proliferation and suppressed the synthesis of glycosaminoglycan.2) Platelet derived growth factor (PDGF) increased intracellular Ca^<2+> concentration ([Ca^<2+>] i) in rabbit chondrocytes and stimulated the synthesis of DNA and glycosaminoglycan. Suramin, an antagonist of PDGF, suppressed the increase of [Ca^<2+>] i and the synthesis of DNA.3) Low density lipoprotein (LDL) increased [Ca^<2+>] i. LDL caused a release of Ca^<2+> from intracellular Ca^<2+> store through production of inositole trisphosphate (iP_3).4) A specific receptor for PDGF existed in the basolateral membrane of dog kidney and PDGF stimulated Ca^<2+>- ATPase.2. Reaserch for the effects of various chemical compounds on the intracellular Ca^<2+> signal system.1) Prostaglandin F2 and angiotensin II (AII), both of which are strong vasoconstrictor, increased [Ca^<2+>] i in VSMC and caused the release of Ca^<2+> from intracellular Ca^<2+> store. Nicorandil, a vasodilator, suppressed the increase of [Ca^<2+>] i induced by prostaglandin F2 and AII.2) Valinomycin, a potassium ionophore, suppressed the release of CA^<2+> from intracellular Ca^<2+> store induced by AII but did not suppress those induced by ionomycin, a Ca^<2+> ionophore. However valinomycin did not sauppress the production of iP_3 induced by AII.3) Nitroglycerin and nicorandil, which are nitrates, stimulated the activities of Ca^<2+>-ATPase in the microsmal fraction of porcine coronary artery smooth muscle cells, but Ca^<2+> channel blockers did not.