Establishment and assessment of postoperative cognitive impairment in intermittent hypoxia rats

Abstract

Objectives: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a chronic disease characterized by repeated episodes of apnea or hypopnea, accompanied by intermittent awakening and sleep disturbances. The incidence of OSAHS is increasing and has become a serious disease. In recent years, more and more evidence shows that OSAHS is closely related to postoperative neurocognitive disorders, and the preparation of models of postoperative cognitive impairment in intermittent hypoxia animals is an important way to study its pathogenesis and intervention targets. This study aims to explore the establishment and evaluation of the animal model of postoperative cognitive impairment in intermittent hypoxia rats.

Methods: A total of 108 male SD rats were randomly divided into 8 groups: a control group (C group, n=27), a surgery group (S group, n=27), an intermittent hypoxia 7 d group (H1 group, n=9), an intermittent hypoxia 14 d group (H2 group, n=9), an intermittent hypoxia 21 d group (H3 group, n=9), an intermittent hypoxia 7 d operation group (O1 group, n=9), an intermittent hypoxia 14 d operation group (O2 group, n=9), and an intermittent hypoxia 21 d operation group (O3 group, n=9). The rats in the H1, H2 and H3 group treated with intermittent hypoxia for 7, 14, and 21 d, respectively. The rats in the O1, O2 and O3 groups received left lateral hepatic lobectomy after 7, 14, and 21 d intermittent hypoxia, respectively. The rats in each group were subjected to open field test, new object recognition test, and Barnes Maze test. The expression of IL-1β mRNA in hippocampus of rats was detected at the 1st day after the surgery.

Results: Compared with the C, S, and H2 groups, the discrimination index in novel object recognition test 6 h and 1 d after the surgery of the O2 group was significantly lower (P<0.05), the latency and errors in Barnes maze at the 1st day and 2nd day after the surgery were increased significantly (P<0.05) and the expression of IL-1β mRNA in hippocampus was significantly increased at the 1st day after the operation (P<0.05). However, there was no difference in the preference index in NORT 6 h and 1 d after the surgery, the latency and errors in Barnes maze and the expression of IL-1β mRNA in hippocampus between the O1 group and the H1 group, the H3 group and the O3 group (all P>0.05).

Conclusions: The rate with intermittent hypoxia 14 d pretreatment with anesthesia and laparotomy could be established the animal model of postoperative cognitive impairment.

Keywords: animal model; intermittent hypoxia; obstructive sleep apnea hypopnea syndrome; postoperative cognitive impairment.

图1

各组大鼠巴恩斯迷宫实验结果 Figure 1 Results of Barnes maze test A: Comparison of control (C), surgury (S), intermittent hypoxia 7 d (H1), and intermittent hypoxia 7 d operation (O1) groups. B: Comparison of C, S, intermittent hypoxia 14 d (H2), and intermittent hypoxia 14 d operation (O2) groups. Compared with C, S, and H2 groups, ****P<0.0001. C: Comparison of C, S, intermittent hypoxia 21 d (H3), and intermittent hypoxia 21 d operation (O3) groups. Compared with C and S groups, *P<0.05.