丁苯酞通过上调海马IGF1R表达改善APP/PS1/Tau小鼠认知功能

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Abstract Objective： To observe the effect of butylphthalide (NBP) on the expression of insulin-like growth factor 1 receptor (IGF1R) in hippocampus of APP/PS1/Tau mice, and to explore the mechanism of IGF1R in NBP treatment of Alzheimer′s disease (AD). Methods： Thirty 8-month-old male APP/PS1/Tau mice were randomly divided into AD group, NBP intervention group and NBP+IGF1R inhibitor intervention group, with 10 mice in each group. Ten 8-month-old C57BL/6J male rats were also taken as the control group. The control group and AD group were given 0.2 mL of vegetable oil by gavage daily, the NBP intervention group was given 120 mg/kg of NBP by gavage daily, and the NBP+IGF1R inhibitor intervention group was given 10 mg/kg of IGF1R inhibitor (NVP-ADW742) by intraperitoneal injection on the basis of the NBP intervention group. After 6 weeks of continuous administration, cognitive behavior of each group was detected by Y maze test, new object recognition test and water maze test. The expressions of Aβ, Tau and p-Tau in hippocampus were detected by Western blotting, Nissl staining was used to evaluate the damage of hippocampal neurons, and immunofluorescence was used to detect the expression of IGF1R in hippocampus. Results： Compared with AD group, NBP intervention group had higher spontaneous alternation rate, higher cognitive index (P<0.05), shorter escape latency of water maze and more times of crossing the platform (P<0.05). Compared with AD group, the protein Aβ and p-Tau in hippocampus of NBP intervention group decreased significantly (P<0.05), the apoptosis of hippocampal neurons decreased significantly (P<0.05) and the expression of IGF1R in hippocampus increased significantly (P<0.05). Compared with NBP intervention group, the expressions of Aβ and p-Tau protein in hippocampus of NBP+IGF1R inhibitor intervention group were higher (P<0.05), the spontaneous alternation rate and cognitive index were significantly decreased (P<0.05), the latency of water maze escape was remarkably prolonged (P<0.05), and the number of crossing platforms was remarkably reduced (P<0.05). Conclusion： NBP could protect AD by up-regulating the expression of IGF1R in hippocampus.

Received: 06 March 2023

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	XU Man
	YU Ming

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XU Man,YU Ming. Butylphthalide improves the cognitive function of APP/PS1/Tau mice by up-regulating the expression of IGF1R in hippocampus[J]. Journal of Jiangsu University(Medicine Edition), 2023, 33(04): 292-296，302.

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http://zzs.ujs.edu.cn/xbyxb/EN/ OR http://zzs.ujs.edu.cn/xbyxb/EN/Y2023/V33/I04/292

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[1]	. [J]. Journal of Jiangsu University(Medicine Edition), 2023, 33(04): 364-368.