Effect and mechanism of blood glucose fluctuation on cognitive function in type 2 diabetic rats

doi:10.3969/j.issn.1006-7795.2021.03.002

Abstract

Abstract: Objective To investigate the effect of blood glucose fluctuation on cognitive function in type 2 diabetic rats and its correlation with oxidative stress in hippocampus. Methods Type 2 diabetes mellitus (T2DM) was established by high sugar and high fat diet combined with intraperitoneal injection of streptozotocin (STZ). The rats were randomly divided into sustained hyperglycemia group (SHG group) (n=12) and intermittent hyperglycemia group (IG group) (n=12). In the IG group, the blood glucose fluctuation model was established by changing the diet habit and life rhythm of rats. The normal blood glucose control group(C group) (n=10) was established. After 6 weeks, the blood glucose levels in each group were measured at 9 points in time within a day, and the mean blood glucose (MBG), standard deviation of daily average blood glucose (SDBG), the largest amplitude of glycemic excursions (LAGE) and mean amplitude of glycemic excursions (MAGE) were obtained. Morris water maze was used to detect the spatial learning and memory ability of the rats in each group at the 10th week. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were measured at the 11th week. The correlation between oxidative stress and cognitive function was analyzed. Results 1) After 6 weeks of blood glucose fluctuation, MBG, SDBG, LAGE and MAGE in the IG group and SHG group were significantly higher than those in the C group(P<0.05). SDBG, LAGE and MAGE in the IG group were higher than those in the SHG group, while MBG was lower than that of SHG group (P<0.05). 2) With regard to the learning and memory ability of rats, the escape latency of diabetic rats (IG group and SHG group) on the 4th day was longer than that in the C group (P<0.05). The number of crossing platform on the 5th day, the activity distance ratio and time ratio of passing through the target quadrant (the quadrant where the platform is in the positioning navigation experiment) were lower than that in the C group (P<0.05). Compared with the SHG group, the times of crossing platform, the activity distance ratio and time ratio of passing through the target quadrant in the IG group on the 5th day were shorter (P<0.05). 3) Detection of oxidative stress index: compared with the C group, the content of MDA in the IG group and SHG group increased, while the content of SOD and GSH-Px decreased (P<0.05). Compared with the SHG group, the content of MDA in the IG group increased, while the content of SOD and GSH-Px decreased (P<0.05). 4) The analysis correlation between oxidative stress index and learning and memory ability showed that MDA was negatively correlated with activity distance ratio, activity time ratio and times of crossing platform (P<0.01), while GSH-Px and SOD were positively correlated with activity distance ratio, activity time ratio and times of crossing platform (P<0.01). Conclusion 1) High glucose and high-fat diet combined with low-dose STZ (30 mg/kg) could successfully establish the model of T2DM, and the blood glucose fluctuation model of T2DM could be successfully established by changing diet habits and biological rhythm. 2) Blood glucose fluctuation is more likely to affect the cognitive function of T2DM rats than continuous hyperglycemia. 3) The fluctuation of blood glucose may aggravate the oxidative stress injury in hippocampus.

Key words: diabetes mellitus, blood glucose fluctuation, oxidative stress, cognitive function

CLC Number:

R587.1

Li Zhi, Zhang Jun, Dai Yuexuan, Qin Mingyang, Liang Furu. Effect and mechanism of blood glucose fluctuation on cognitive function in type 2 diabetic rats[J]. Journal of Capital Medical University, 2021, 42(3): 347-353.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2021.03.002

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2021/V42/I3/347

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