Page 108 - 《中国药科大学学报》2025年第4期

504 学报 Journal of China Pharmaceutical University 2025, 56(4): 498 − 506 第 56 卷

A Adrb1 +/+ n.s. Adrb1 +/m B Vehicle; Metoprolol
Adrb1 +/+ n.s. Adrb1 +/m
** ****
80 60 ****
**
60
40
EF/% 40 FS/%

20
20

0 0
5 10 20 5 10 20 5 10 20 5 10 20

Figure 3 Metoprolol had a pronounced effect on cardiac function. (A and B) Left ventricular ejection fraction (EF) (A) and shortened
fraction (FS) (B) were calculated in 1 hour after drug administration in wild-type and mutant mice. **P<0.01, ****P<0.0001. n.s, not
significant. Three-way ANOVA, post-hoc Tukey's multiple comparisons test
A

Vehicle Drug
day1 day2
6 h calculation 6 h calculation
B 250 ** *** C 300 ** *** D 50 n.s. * E 200 ** n.s. ****
Total wakefulness time/min 200 Total NREM time/min 250 Total REM time/min 40 Wakefulness bouts 150

150
30
200
100
20
100
150
50
10
50
0
Adrb1 +/+ Adrb1 +/m 100 Adrb1 +/+ Adrb1 +/m 0 Adrb1 +/+ Adrb1 +/m 0 Adrb1 +/+ Adrb1 +/m
F n.s. G H
n.s.
* **** *
150 80 250 ** ****
*** 200 Vehicle;
60
NREMS bouts 100 REMS bouts 40 Micro arousal No. 150 Nebivolol
100
50
20
0 0 50 0
Adrb1 +/+ Adrb1 +/m Adrb1 +/+ Adrb1 +/m Adrb1 +/+ Adrb1 +/m
Figure 4 Nebivolol has a pronounced effect on sleep. (A) Schematic workflow of experiment setup. (B-D) Total time of wakefulness (B),
NREMS (C) and REMS(D) were calculated within 6 hours after drug treatment for wild-type (n=7) and mutant mice(n=10). (E-H) Changes
of wakefulness bouts (E), NREMS bouts (F) , REMS bouts (G) and micro arousal numbers (H) were calculated within 6 hours in wild-type
mice and mutant mice. *P<0.05, **P<0.01, ***P<0.001, ****P<0.000 1, n.s, not significant. Two-way ANOVA, post-hoc Sidak's multiple
comparisons test. Error bars represent ± SEM

Table 1 Summary of sleep changes after β-blockers treatment within 6 hours
Duration (drug vs. vehicle) Bouts (drug vs. vehicle)
Name Dose(mg/kg)
Wake NREM REM Wake NREM REM
Metoprolol 10 --- --- --- --- --- ---
Metoprolol 80 ↑ ↓ ↓ --- --- ↓
Nebivolol 10 --- --- --- ↑ ↑ ---
Propranolol 10 ↑ ↓ ↓ ↑ ↑ ↓