氯沙坦对大鼠血管损伤性重塑的影响及其与细胞凋亡的关系

Effect of losartan on remodeling of injured artery and its relation to apoptosis in rats

目的 :探讨血管紧张素Ⅱ (AngⅡ )受体拮抗剂氯沙坦对血管损伤性重塑的作用及其内在机制。 方法 :将Wistar大鼠随机分为假手术组 (6只 )、氯沙坦组 (2 0只 )及对照组 (2 1只 ) ,后两组大鼠行胸主动脉球囊损伤术 ,术后不同时间段处死。三组均进行苏木精 伊红染色及计算机图像分析 ,Tunel标记法检测细胞凋亡率 ,免疫组化方法检测血管壁凋亡相关基因表达物Fas、Fas L、Bcl 2、Bax的变化。结果 :对照组术后第 7、14天损伤血管管壁横截面积增加明显 ,分别为 (0 .4 84± 0 .180 )mm2 和 (0 .6 6 1± 0 .2 4 1)mm2 ,与假手术组比较 ,P <0 .0 5。术后第 14天 ,氯沙坦组损伤血管管壁横截面积为 (0 .384± 0 .0 90 )mm2 ,与对照组比较 ,管壁增生程度显著降低。术后第 7天 ,管壁面积增生比与细胞凋亡率之间有负相关性 (r =- 0 .5 86 ,P <0 .0 5 ) ,氯沙坦组的细胞凋亡率显著高于对照组。氯沙坦组与对照组比较 ,术后第 7天管壁组织内Fas L表达增加 ,Bcl 2表达降低 (P <0 .0 5 )。结论 :AngⅡ受体拮抗剂氯沙坦可有效减轻大鼠动脉损伤后的血管增生性重塑。其机制可以与促进细胞Fas的表达、抑制Bcl 2的表达 。

Objective:To examine the effect of losartan on vascular remodeling after artery injury and the relation of losartan to apoptosis-related gene expression on the rat models of balloon injury.Methods:Male Wistar rats were randomized to a standard diet or a diet supplemented with 20mg·kg -1·d -1 losartan. Animals were sacrificed at 2, 7 and 14 days respectively after injury. The intimal and medial area, apoptosis and the expression of Bcl-2, Bax, Fas, Fas-L in injured vessel were measured.Results:Seven days and 14 days after angioplasty, the intimal and medial areas were significantly increased in control group as compared to artificial group. 14 days after angioplasty, the areas decreased significantly in losartan group as compared to control group. The increase of apoptosis was associated with the decrease of intimal and medial areas 7 days post injury in two group. The expression of Fas increased, and the expression of Bcl-2 decreased in losartan group.Conclusion:Losartan inhibited artery wall remodeling in the rat model of artery injury by mechanisms involving increase in expression of Fas-L and decrease in expression of Bcl-2 which both contributed to VSMC apoptosis.