沙库巴曲缬沙坦对原发性高血压的治疗效果及机制研究

Therapeutic effect and mechanism of sacubitril/valsartan in patients with essential hypertension

目的:探讨沙库巴曲缬沙坦对原发性高血压(EH)的治疗效果,并分析其可能机制。方法:随机数字表法将168例EH患者均分为两组,其中对照组服用替米沙坦降低血压,观察组服用沙库巴曲缬沙坦降血压,两组均持续服用12周。比较两组治疗前后血压(收缩压、舒张压)、氧化应激[晚期氧化蛋白产物(AOPP)、超氧化物歧化酶(SOD)、一氧化氮(NO)]、炎症反应[白细胞介素-1(IL-1)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]、PI3K/AKT信号蛋白[PI3K、AKT、磷酸化丝氨酸苏氨酸蛋白激酶(p-AKT)]及血管内皮功能[血管内皮细胞(VEC)数目、VEC表达频率、血管内皮舒张功能(FMD)、血管内皮功能障碍]变化情况。结果:与治疗前比,两组治疗后收缩压、舒张压、AOPP、NO、IL-1、IL-6、TNF-α、p-AKT、血管内皮功能障碍发生率均明显下降,血清SOD、PI3K、AKT、VEC数目、VEC表达频率、FMD明显增大(均P<0.05)。观察组治疗后的收缩压、舒张压、AOPP、NO、IL-1、IL-6、TNF-α、p-AKT、血管内皮功能障碍发生率均明显低于对照组,血清SOD、PI3K、AKT、VEC数目、VEC表达频率、FMD明显大于对照组(均P<0.05)。结论:沙库巴曲缬沙坦具有良好的降血压作用,同时可通过调节PI3K/AKT信号通路,抑制EH体内氧化应激和炎症反应,促进患者VEC增殖,逆转血管内皮损伤。

Objective:To investigate the therapeutic effect of sacubitril/valsartan on essential hypertension(EH)and its possible mechanism.Methods:A total of 168 EH patients were divided into two groups by random number table method.Telmisartan was taken in control group to reduce blood pressure,and sacubitril/valsartan was taken in observation group to reduce blood pressure,and both groups continued to take medicine for 12 weeks.Blood pressure(systolic blood pressure,diastolic blood pressure),oxidative stress(advanced oxidized protein product[AOPP],superoxide dismutase[SOD],nitric oxide[NO]),inflammatory response(interleukin-1[IL-1],interleukin-6[IL-6],tumor necrosis factor-α[TNF-α]),phosphatidyl inositol 3 kinase/serine threonine protein kinase(PI3K/AKT)signaling protein(PI3K,AKT,phosphorylated serine threonine protein kinase[p-AKT])and vascular endothelial function(number of vascular endothelial cells[VEC],frequency of VEC expression,vascular endothelial diastolic function[FMD],vascular endothelial dysfunction)were compared between the two groups before and after treatment.Results:Compared with before treatment,systolic blood pressure,diastolic blood pressure,AOPP,NO,IL-1,IL-6,TNF-α,p-AKT and incidence of vascular endothelial dysfunction were significantly decreased in two groups after treatment,and serum SOD,PI3K,AKT,VEC number,VEC expression frequency and FMD were significantly increased(all P<0.05).The systolic blood pressure,diastolic blood pressure,AOPP,NO,IL-1,IL-6,TNF-α,p-AKT and incidence of vascular endothelial dysfunction in the observation group were significantly lower than those in the control group,while the serum SOD,PI3K,AKT,VEC number,VEC expression frequency and FMD were significantly higher than those in the control group(all P<0.05).Conclusion:Sacubitril/valsartan has a good effect on lowering blood pressure,and can inhibit oxidative stress and inflammation in EH by regulating PI3K/AKT signaling pathway,promote VEC proliferation and reverse vascular endothelial injury.