氟伐他汀调节SHR大鼠血管平滑肌细胞钙泵的表达对血管重构的影响及作用机制

目的探讨氟伐他汀（fluvastatin，Flu）对小牛血清（CS）干预的高血压大鼠胸主动脉血管平滑肌细胞增殖及血管重构的影响并初步探讨其可能的机制。方法CS、Flu和甲羟戊酸（mevalonic acid，Meva）处理血管平滑肌细胞4d，将细胞分为SHR组、SHR＋20％CS组、SHR＋20％CS＋Flu组和SHR＋20％CS＋Flu＋Meva组，采用MTT检测细胞的增殖能力，Transwell检测细胞的迁移能力，体外管样实验、天狼星红染色以及免疫荧光的方法分别检测细胞的管样结构的生成能力、胶原纤维以及F-actin的表达，Western印迹检测PMCA、SERCA和LTCC的表达。结果Flu能够抑制CS促进的VSMCs增殖效应、迁移能力，管样结构生成，胶原蛋白表达，以及骨架蛋白的聚合，并下调VSMCs中PMCA的表达，上调SERCA和LTCC的表达，而Meva则对Flu的作用进行逆转。结论氟伐他汀对CS诱导的VSMCs增殖及血管重构产生抑制，该过程可能是通过调节钙泵的表达实现的，而Meva代谢途径可能在其中发挥了重要的作用。

Effect and Mechanism of Fluvastatin on Ca2 + ATPase Expression in Vascular Smooth Muscle Cells to the Rearrangement of Vascular

Objective To investigate the effect offluvastatin （Flu） induced by CS on the proliferation of vascular smooth muscle cells （VSMCs） and the rearrangement of vascular and studies the possible mechanism. Methods We divided VSMCs into four groups： SHR group, SHR ＋ 20% CS group, SHR ＋ 20% CS ＋ Flu group ; and SHR ＋ 20% CS ＋ Flu ＋ Meva group. The proliferation of VSMCs was detected by MTT assay, and the migratory ability changes were analyzed in transwell. We analyzed tube formation ability in Matrigel, and examined collagen used sirius red saturated picric acid staining, and detected the expression of F-actin by immunofluorescence. Expressions of PMCA, SERCA and LTCC were analyzed by Western blot. Results Fluvastatin can inhibit the proliferative rate, migratory ability, the formation of tube, the expression of collagen and F-actin which was promoted by CS. The Western blot results showed that fluvastatin could down-regulate the expression of PMCA and up-regulated the expression of SERCA and LTCC. Conclusion Fluvastatin can suppress the proliferation and rearrangement of vascular effect of VSMCs which were induced by CS, it is may be achieved through the expression of Ca^2＋ ATPase, and the mevalonate pathway may be involved in this process.