【摘要】 目的:探讨内皮间充质转化(endothelial-to-mesenchymal transition,EMT)是否促进自发性高血压大鼠主动脉纤维化及降压治疗对其干预作用。方法:将24只雄性自发性高血压大鼠(spontaneously hypertensive rats,SHR)随机分为SHR组(S组,蒸馏水灌胃)、哌唑嗪组(P组,哌唑嗪5 mg/(Kg×d)灌胃)和氯沙坦组(L组,氯沙坦10 mg/(Kg×d)灌胃),8只雄性WKY大鼠(W组,蒸馏水灌胃)作为对照组,各组分别干预8周后,通过Masson染色检测各组大鼠主动脉纤维化程度,免疫荧光染色及Western Blot检测各组大鼠主动脉I型胶原、CD31及FSP1蛋白表达变化。结果:Western blot及Masson染色显示从L组、P组到S组大鼠主动脉I型胶原含量依次增多,且主动脉壁厚度均显著大于W组(P<0.05),但P组与L组大鼠主动脉管壁厚度无统计学差异(P=0.818);免疫荧光染色表明,各组高血压大鼠主动脉均存在FSP1及CD31共表达(FSP+CD31+)细胞,且从L组、P组到S组FSP+CD31+细胞依次增多;Western Blot检测表明,从W组、L组、P组到S组,CD31蛋白表达量逐渐降少,FSP1蛋白表达量依次增加,差异有统计学意义(P<0.05)。结论:EMT可能参与了自发性高血压大鼠的主动脉纤维化,氯沙坦和哌唑嗪可能通过抑制EMT减轻主动脉纤维化。更多还原

【Abstract】 Objective: To investigate whether Endothelial-to-mesenchymal transition contributed to artery fibrosis in Spontaneously hypertensive rats(SHRs) and whether antihypertensive treatment could attenuate the effect. Methods: Wistar Kyoto(WKY) rats and spontaneously hypertensive rats were used in the experiment. 24 male SHRs were divided into three groups randomly, and received phosphate buffer, prazosin and losartan respectively, 8 male WKYs served as controls. 8 weeks later, all rats were sacrificed and their aortas were collected for further research. Masson trichrome stain was used to detect the deposition of collagen fiber,immunofluorescence was performed to evaluate cells that co-expressed CD31 and fibroblast specific protein-1(FSP-1), and Western Blot was applied to measure the expression of protein CD31, FSP-1 and collagen- Ⅰ. Results: Increased interstitial fibrosis was proved in SHRs’ aortas both by Masson trichrome stain and Western Blot, while the phenomenon was diminished by the intervention of prazosin and losartan(P<0.05). The FSP+CD31+cells were found in all SHRs aortic immunofluorescence, FSP-1 and were markedly upregulated in SHRs, while CD31 was reduced significantly, and samely the phenomena were inhibited by prazosin and losartan. Conclusions: The fibrosis of SHRs’ aortas may be induced, at least partially, by EMT. Meanwhile, EMT could be inhibited by the intervention of prazosin and losartan, and losartan was more effective than prazosin.更多还原