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| Changes of clock genes in the brain of vascular dementia rats in different time courses and the regulatory effect of cornel iridoid glycoside |
| ZHENG Cengceng ZHANG Li LI Yali LI Lin ZHANG Lan YANG Cuicui |
Department of Pharmacy, Xuanwu Hospital of Capital Medical University Beijing Engineering Research Center for Nervous System Drugs Beijing Institute for Brain Disorders Key Laboratory for Neurodegenerative Diseases of Ministry of Education National Clinical Research Center for Geriatric Diseases, Beijing 100053, China
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Abstract Objective To observe the changes of clock genes in the brain of vascular dementia rats in different time courses and the regulatory effect of cornel iridoid glycoside (CIG)． Methods A total of 45 SPF male SD rats, 6-8 weeks old, weighing 150-180 g were selected, and 15 rats were selected as Sham operation group, the rest were established by 2-vessel occlusion (2VO) to establish the chronic cerebral ischemia model. After successful modeling, the Sham operation animals were divided into three groups, and the model animals were divided into six groups by random number table method, with five animals in each group. The specific groups were modeling 1 month group (Sham group, 2VO group, 2VO+CIG60 group, 2VO+CIG120 group, 2VO+ Butylphthalide group); modeling 1.5 months group (Sham group, 2VO group); modeling 3 months group (Sham group, 2VO group). After six hours of modeling, CIG 60 mg/(kg·d) was gavaged in 2VO+CIG60 group, CIG 120 mg/(kg·d) was gavaged in 2VO+CIG120 group, Butylphthalide 100 mg/(kg·d) was gavaged in 2VO+Butylphthalide group, and Sham group and 2VO group were gavage with the same amount of normal saline. At 1, 1.5, and 3 months after modeling, the hypothalamus and midbrain of rats were taken to detect the levels of clock genes CRY1, PER1, PER2, and NPAS2 mRNA, the changes of clock genes were observed. Results In hypothalamus, compared with Sham group, PER2 mRNA in 2VO group was decreased at 1 month after modeling (P＜0.01); clock gene PER2 mRNA and NPAS2 mRNA in 2VO group were increased at 1.5 months after modeling (P＜0.05 or P＜0.01). In midbrain, compared with Sham group, CRY1 mRNA and PER1 mRNA in 2VO group were higher at 1 month after modeling (P＜0.05 or P＜0.01); PER2 mRNA in 2VO group was increased at 3 months of modeling (P＜0.05). In hypothalamus, compared with Sham group, PER2 mRNA in 2VO group was decreased (P＜0.01); compared with 2VO group, NPAS2 mRNA in 2VO+CIG60 group was increased, PER1 mRNA in 2VO+CIG120 group was decreased (P＜0.05). In midbrain, compared with Sham group, CRY1 mRNA and PER1 mRNA in 2VO group were increased (P＜0.05 or P＜0.01); compared with 2VO group, CRY1 mRNA in 2VO+CIG120 group was decreased (P＜0.01). Conclusion Disordered expression of clock genes in the hypothalamus and midbrain of vascular dementia model rats causes disruption of the feedback loop that regulates circadian rhythm, and CIG can correct the disordered expression of clock genes in the hypothalamus and midbrain.
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