YC-1对肝部分切除术后老年小鼠认知功能及海马神经元凋亡的影响

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Abstract Objective: To investigate the effect of 3-(5’-hydroxymethyl-2’-furyl)-1-benzylindazole (YC-1) on cognitive function and hippocampal neuronal apoptosis in aged mice after partial hepatectomy, and to discuss the role of hypoxia inducible factor-1α (HIF-1α) in the mechanism of post-operative cognitive dysfunction (POCD). Methods: Forty-eight healthy male type C56BL/6 mice, aged 18 months, weighing 25-35 g, were used in the study. The mice of either type were randomly divided into 3 groups (n=16), using a random number table: sham operation group (sham group), operation group (operation+NS group) and HIF-1α inhibitor YC-1 group (operation+YC-1 group). Operation models were established by partial hepatectomy and the YC-1 treatment was given to the operation group. In sham group, the mice were incised and given surgical suture on the same surgical site in partial hepatectomy. Then each group was divided 1 d and 3 d respectively (n=8). Hidden and cued platform Morris water maze training and testing was used to observe spatial memory abilities on 1st or 3rd day. After the Morris water maze test, mice in each group were sacrificed after anesthesia. The hippocampus was separated for detection of the expression of HIF-1α and Bax, Bcl-2, activated caspase-3 by Western blot. Results: Compared with sham group, the latency for mice to find the flat was obviously prolonged and the time taken to cross the flat were decreased in the Morris water maze test. The expression of HIF-1α, Bax, activated caspase-3 were significantly increased and Bcl-2 was decreased at 1 day and 3 days in the operation group (P<0.01). Compared with the operation+NS group, the latency to find the flat was obviously decreased and the times to cross the flat were increased; the expression of HIF-1α, Bax, activated caspase-3 were significantly decreased and Bcl-2 increased at 1 day and 3 days in the operation+YC-1 group. Conclusion: YC-1 can improve the cognitive function and ameliorate the hippocampal neuronal apoptosis after partial hepatectomy. It was induced by down regulation of HIF-1α protein. HIF-1α is partially involved in the mechanism of POCD induced hippocampal neuronal apoptosis in mice.

Key words： YC-1 hypoxia inducible factor-1α partial hepatectomy cognitive function;apoptosis hippocampus mice

Received: 28 June 2018

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	GE Yeying
	WANG Xiuzhen
	YUAN Na
	YUAN Liyong
	CHEN Jie

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2018/V48/I12/888

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