摘要
目的探讨氯沙坦对心力衰竭(HF)患者外周血内皮祖细胞(EPC)的影响及对磷脂酰肌醇-3激酶/丝氨酸/苏氨酸蛋白激酶/内皮型一氧化氮合酶(PI3K/Akt/e NOS)通路的干预。方法选取2016年1月至2016年10月我院收治的HF患者随机分为对照组和治疗组,每组各43例。对照组予以常规抗HF治疗,治疗组在此基础上口服氯沙坦一日50 mg。入院及治疗8周后,测定患者左室射血分数(LVEF)、血浆脑钠肽(BNP)水平及EPC数目。体外培养HF患者EPC,观察比较空白组、氯沙坦组和PI3K抑制剂组EPC细胞增殖、凋亡和迁移情况,以及EPC的Akt和eNOS的表达情况。结果与治疗前比较,治疗后两组LVEF升高,BNP水平降低,EPC数目增加(P<0.05);且治疗组改善效果优于对照组,组间差异具有统计学意义(P<0.05)。与空白组和PI3K抑制剂组比较,氯沙坦组各时间点OD570值升高,细胞凋亡率降低,迁移距离增加,差异有统计学意义(P<0.05);氯沙坦组Akt和eNOS表达量明显升高,差异有统计学意义(P<0.05)。结论氯沙坦能明显改善心衰患者LVEF、BNP水平和EPC数量,促进EPC细胞增殖和迁移,减少EPC细胞凋亡,其主要机制可能与上调PI3K/Akt/eNOS通路中Akt和e NOS表达有关。
Objective To investigate the effects of losartan on endothelial progenitor cells(EPCs) in heart failure(HF) patients, and its intervention on PI3K/Akt/eNOS pathway. Methods Eighty-six HF patients, who were treated in our hospital from January 2016 to October 2016, were selected and randomly assigned into control group(n=43) and treatment group(n=43). The control group was treated with conventional anti-HF treatment, while the treatment group was treated with losartan 50 mg/d. On admission and 8 weeks after treatment, the LVEF, the brain natriuretic peptide(BNP) and the number of EPCs in peripheral blood were measured. EPCs were isolated from HF patients and cultured in vitro. The experiment was divided into 3 groups: blank group, losartan group and PI3K inhibitor group. The proliferation, apoptosis and migration of EPCs, and the expression of Akt and eNOS were detected. Results Compared with before treatment, the BNP level was decreased(P<0.05), and the LVEF level and the EPCs number were increased(P<0.05). However, the treatment group was improved significantly better than the control group(P<0.05). The apoptosis rate of the losartan group was significantly lower than that of the blank group and the PI3K inhibitor group(P<0.05). The OD_(570) values at each time point and the migration distance of EPCs in the losartan group were significantly higher than those of blank group and PI3K inhibitor group(P<0.05). The expression of Akt and eNOS of losartan group were higher than those of PI3K inhibitor group and blank group(P<0.05). Conclusion Losartan can significantly improve LVEF, BNP and EPCs number in HF patients. It can promote EPCs cell proliferation, reduce apoptosis and increase cell migration. Its main mechanism may be related to upregulation of Akt and eNOS expression in the PI3K/Akt/eNOS pathway.
出处
《世界临床药物》
CAS
2017年第4期242-247,共6页
World Clinical Drug
