氯沙坦对大鼠动脉损伤后平滑肌细胞凋亡及Fas抗原及其配体的影响

Effects of losartan on apoptosis of vascular smooth muscle cells and Fas antigen,Fas ligend expressions after artery iniury

①目的探讨氯沙坦对大鼠颈动脉损伤后平滑肌细胞凋亡和相关基因Fas抗原与Fas配体的影响及其对临床预防经皮冠状动脉成形术后再狭窄的可行性。②方法将42只雄性W istar大鼠,随机分为氯沙坦实验组(n=21)及对照组(n=21),实验动物均行左侧颈总动脉球囊剥脱损伤内皮模型,术后于不同时间段取损伤段血管,均进行苏木精-伊红染色及计算机图像分析;Tunnel标记法检测平滑肌细胞凋亡率;免疫组化法测定Fas抗原及其配体在血管壁中的表达。③结果对照组于术后第7、14天损伤血管壁面积增加,相同时间段内两组比较,结果氯沙坦实验组管壁增生程度较对照组显著降低(P(0.05);术后第7、14天氯沙坦实验组的细胞凋亡率显著高于对照组(P(0.05);管壁中Fas抗原、Fas配体的表达较对照组明显增加。④结论血管紧张素Ⅱ受体拮抗剂氯沙坦可以通过Fas系统调节损伤段血管平滑肌细胞的凋亡而抑制新生内膜的形成。

Objective To investigate the effect of losartan on the apoptosis and related gene Fas antigen and Fas ligand of vascular smooth muscle cells（VSMCS） in injured artery of rats. Methods 42 male Wistar rats were divided randomly into losartan group（ n = 21,5mg. kg. d） and control group（ n = 21 ）. Endothelium denudation injured in left carotid both groups were made. Animals were killed at 3,7,14 days after operation. Fas and Fasl antigen were detected by immunohistochemistry in the two groups. Apoptotic VSMCS were stained in situ by terminal deoxynucleotidyl transferase mediated - dUTP nick end labeling（TUNEL）. We caculated the area of vascular walls with computer analysis of pathological graph system. Results 7 days and 14 days after injured,the area of vascular walls were significantly decreased in losartan group as compared with control group. The VSMCS apoptotic rate was significantly lower in losartan group as compared to control group after 7 and 14 days. The expression of Fas and Fasl were significantly increased in losartan group as compared to control group after 7 and 14 days. Conclusion Losartan may probably inhibited artery wall remodeling in the rat model of artery injury by mechanism involving promoting VSMCS apoptosis through Fas system.