NMDA受体NR2A、NR2B亚基在戊四氮诱导慢性癫痫大鼠中的作用

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Abstract Objective: To explore the role and mechanism of N-methyl-D-aspartic acid (NMDA) receptor NR2A and NR2B subunits in pentetrazol (PTZ) induced chronic epileptic rats. Methods: Forty-eight male SD rats were randomly divided into control group, PTZ group, PTZ+MK-801 group, PTZ+NVP group, and PTZ+Ifenprodil group. Rats were daily kindled by intraperitoneal injection of 35 mg/(kg·d) PTZ for 28 days. Half an hour before PTZ kindle, rats were given intraperitoneal injection of 3.5 mL/(kg·d) saline, 0.1 mg/(kg·d) MK-801, 5.0 mg/(kg·d) NVP, and 10 mg/(kg·d) Ifenprodil, respectively. Seizure scores according to Racine standard were recorded for 28 consecutive days. All rats were sacrificed on the 29th day. Nissl’s staining was used to evaluate neuron loss of hippocampal CA1, CA3, and DG areas. Western blot was used to detect the expression of NR2A, NR2B subunits. Results: Compared with the PTZ group, MK-801 and NVP could reduce the intensity of convulsion attack in pentetrazol induced chronic epileptic rats, while Ifenprodil produced no such effect. Compared with the control group, hippocampal neurons in the PTZ group lost significantly; while compared with the PTZ group, hippocampal neuron losing in MK-801, NVP, and Ifenprodil groups were light, of which, MK-801 and NVP were the lightest. Compared with the control group, the levels of both NR2A and NR2B subunits in hippocampal decreased after convulsion attack and the decline was most pronounced in the PTZ group. Level of NR2A subunit in PTZ+NVP group was higher than PTZ group, while levels of NR2B subunit in PTZ+MK-801, PTZ+NVP and PTZ+Ifenprodil groups were higher than PTZ group. Conclusion: Non-selective inhibition of NMDA receptor and selective inhibition of NR2A subunit could reduce the intensity of convulsion attack and improve hippocampal neuron losing in pentetrazol induced chronic epileptic rats, while selective inhibition of NR2B subunit could only improve hippocampal neuron losing. This study suggested that the convulsion attack could be related to NR2A subunit, and the damage of neurons could be related to both NR2A and NR2B subunit.

Key words： epilepsy pentetrazol NMDA receptors NR2A subunit NR2B subunit rats

Received: 10 June 2018

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	XU Huiqin
	DU Yanru
	SHEN Jingzan
	LIN Jiahe
	DING Siqi
	ZHENG Rongyuan
	WANG Xinshi
	WANG Li
	YE Mengqian

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2018/V48/I12/866

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