目的 探讨比索洛尔不同服用时间对慢性心衰患者心率和神经内分泌因子昼夜节律的影响。方法 入选96例慢性心衰患者和50例健康者分别作为研究组与对照组，同时根据比索洛尔不同服药时间将研究组分成日间服药组（7：00~8：00）与夜间服药组（19：00~20：00），每组48例。比较研究组与对照组间的动态心电图结果、血浆去甲肾上腺素（NE）、血管紧张素Ⅱ（AngⅡ）、醛固酮及肾上腺素水平，以及2个亚组治疗前后上述指标的变化。结果 与对照组比较，研究组24 h心率明显加快，差异有统计学意义（P<0.05）；夜昼心率比值增大，非杓型心率比例明显增加，差异有统计学意义（P<0.05）；NE、AngⅡ、醛固酮、肾上腺素水平明显升高，差异有统计学意义（P<0.05），研究组神经内分泌因子不存在昼夜节律。与治疗前比较，日间服药组和夜间服药组24 h心率均明显减慢，差异有统计学意义（P<0.05）；夜昼心率比值下降，非杓型心率比例降低，NE、AngⅡ、醛固酮、肾上腺素水平均明显降低，组内差异均有统计学意义（P<0.05）；组间比较均无明显差异，且均未恢复昼夜节律。结论 慢性心衰患者心率和神经内分泌因子的昼夜节律消失，夜间服用比索洛尔较日间服用并不会明显恢复其心率和神经内分泌因子的昼夜节律。

Objective Toinvestigate the effects of bisoprolol different taking timeon circadian rhythm of heart rate and neuroendocrine factors in patients with chronic heart failure. Methods A total of 96 patients with chronic heart failure and 50 healthy subjects were enrolled as the case group and the control group, and the case group were divided into day taking medicine group (7:00-8:00) and night taking medicine group (19:00-20:00) according to different administration time of bisoprolol,48 cases in each group. The dynamic ECG results, plasma norepinephrine (NE), angiotensin Ⅱ (Ang Ⅱ), aldosterone and epinephrine levels were compared between the case group and the control group, and the changes of the above indexes before and after treatment were compared between the 2 subgroups. Results Compared with the control group, in the case group, the heart rate of 24 h was significantly accelerated (P < 0.05). The ratio of heart day and night rate increased, and non dipper heart rate increased significantly (P < 0.05); the levels of NE, AngⅡ, aldosterone and epinephrine increased significantly (P < 0.05), and there was no circadian rhythm in the neuroendocrine factors in the case group (P > 0.01). Compared with the before treatment, the heart rate of 24 h were significantly slower in the day taking medicine group and the night taking medicine group (P < 0.05), the rate of heart rate decreased day and night, non dipper heart rate reduction, the levels of NE, AngⅡ, aldosterone and epinephrine decreased obviously (P < 0.05), and the circadian rhythm was not recovered (P > 0.01). Conclusion Circadian rhythms of heart rate and neuroendocrine factors disappear in patients with chronic heart failure,and taking bisoprolol at night do not significantly restore the circadian rhythm of heart rate and neuroendocrine factors compared with those taken during the day.