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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 effect of losartan on peripheral blood endothelial progenitor cells (EPCs) in patients with heart failure (HF) and the effects of phosphatidylinositol 3-kinase / serine / threonine protein kinase / PI3K / Akt / e NOS) pathway. Methods From January 2016 to October 2016, HF patients admitted to our hospital were randomly divided into control group and treatment group, with 43 cases in each group. The control group was given conventional anti-HF treatment, and the treatment group received losartan 50 mg on the basis of this day. After hospitalization and treatment for 8 weeks, the patients’ left ventricular ejection fraction (LVEF), plasma brain natriuretic peptide (BNP) level and EPC number were determined. The EPC of HF patients were cultured in vitro. The proliferation, apoptosis and migration of EPCs in EPC, PI3K inhibitor group and losartan group were observed, and the expressions of Akt and eNOS in EPCs were compared. Results Compared with those before treatment, the LVEF, BNP level and the number of EPCs increased in both groups after treatment (P <0.05). The improvement in the treatment group was better than that in the control group. There was significant difference between the two groups (P <0.05). Compared with the blank group and the PI3K inhibitor group, the OD570 value of Losartan group increased at each time point, the apoptosis rate decreased, the migration distance increased, the difference was statistically significant (P <0.05); Losartan group Akt and eNOS The expression was significantly increased, the difference was statistically significant (P <0.05). Conclusion Losartan can significantly improve the levels of LVEF and BNP and the number of EPC in heart failure patients, promote the proliferation and migration of EPCs and reduce the apoptosis of EPCs. The main mechanism may be related to the up-regulation of Akt and eNOS expression in PI3K / Akt / eNOS pathway .