CAJ | 학술논문

目的研究血管紧张素ⅡAT1-R阻滞剂洛沙坦对自发性高血压大鼠(SHR)血管平滑肌细胞(VSMC)凋亡及凋亡基因Bax、Bcl-2的影响.方法末端标记法(TUNEL)检测细胞凋亡及RT-PCR、免疫组化方法分别检测Bax、Bcl-2基因及其蛋白的表达.结果从(12～24)周龄,SHR VSMC凋亡逐渐减低,24周龄时,凋亡指数(APOI)低于同周龄正常血压大鼠(WKY)(P<0.05);洛沙坦应用8周和12周,使APOI增加71%、35%(P<0.05).随大鼠周龄增加,SHR胸主动脉Bax基因表达逐渐下调,与APOI变化趋势一致.洛沙坦降压治疗可使SHR胸主动脉Bax蛋白表达上调,Bcl-2蛋白下调.结论洛沙坦长期降压治疗促进Bax蛋白表达和/或抑制Bcl-2蛋白表达,其机制可促进VSMC凋亡.
목적연구혈관긴장소ⅡAT1-R조체제락사탄대자발성고혈압대서(SHR)혈관평활기세포(VSMC)조망급조망기인Bax、Bcl-2적영향.방법말단표기법(TUNEL)검측세포조망급RT-PCR、면역조화방법분별검측Bax、Bcl-2기인급기단백적표체.결과종(12～24)주령,SHR VSMC조망축점감저,24주령시,조망지수(APOI)저우동주령정상혈압대서(WKY)(P<0.05);락사탄응용8주화12주,사APOI증가71%、35%(P<0.05).수대서주령증가,SHR흉주동맥Bax기인표체축점하조,여APOI변화추세일치.락사탄강압치료가사SHR흉주동맥Bax단백표체상조,Bcl-2단백하조.결론락사탄장기강압치료촉진Bax단백표체화/혹억제Bcl-2단백표체,기궤제가촉진VSMC조망.
Objective To explore the effects of the antihypertensive therapy with Losartan on vascular smooth muscle cell (VSMC) apoptosis and apoptotic gene Bax, Bcl-2 in spontaneously hypertensive rats (SHRs). Methods Apoptosis was identified by in situ TDT-mediated dUTP nick end labeling (TUNEL). The expression of Bax and Bcl-2 gene was detected by RT-PCR, and their protein expression was assessed by immunohistochemistry.Results The results showed that the APOI of VSMC apoptosis in SHR-C decreased gradually with their aging from 12 weeks old to 24 weeks old;and was lower than that of age-matched WKY at the age of 24 weeks (P<0.05). Losartan increased APOI by 71%, 35% after oral use for 8 weeks and 12 weeks(P<0.05). Expression of proapoptotic gene Bax in thoracic aorta tissue of SHR-C decreased gradually from 12 weeks to 24 weeks with the same trend as that of APOI.The antihypertensive therapy by losartan might make the upregulation of the expression of Bax protein in thoracic aorta and the downregulation of Bcl-2 protein.Conclusion The long-term antihypertensive therapy with Losartan stimulated the expression of Bax protein and/or inhibits the expression of Bcl-2 protein.Its mechanism might be to promote the vascular smooth muscle cell apoptosis.