大麻素受體激動劑預處理對大鼠局灶性腦缺血再灌注損傷的保護作用

Neuroprotective effect of preconditioning with cannabinoid receptor agonist WIN 55,212-2 on focal cerebral ischemia: experiment with rats

doi：

摘要：

目的 探討大麻素(CB)受體激動劑WIN 55,212-2預處理對大鼠局灶性腦缺血的保護作用.方法采用大鼠大腦中動脈栓塞(MCAO)致局灶性腦缺血模型,將50只雄性SD大鼠隨機分為5組:對照組(Con組),行線栓法斂大腦中動脈栓塞(MCAO)前24 h腹腔注射生理鹽水(NS)0.3ml;WIN 55,212-2預處理組(WIN1～3),分別于MCAO前24 h腹腔注射WIN 55,212-2 0.3,1和3rag/kg;DMSO組,于MCAO前24 h腹腔注射二甲基亞砜(DMSO,WIN 55,212-2的溶劑)0.3 ml.觀察MCAO120 min再灌注24,48和72 h后神經功能評分(NFS)和再灌注72 h腦梗死容積百分比.結果 WIN 55,212-2預處理組大鼠NFS明顯高于DMSO組和Con組(P<0.05),腦梗死容積百分比明顯小于DMSO組和Con組(P<0.05).WIN2組和WIN3組的腦梗死容積百分比明顯小于WIN1組,NFS明顯高于WIN1組(P<0.05),WIN2組和WIN3組的NFS和腦梗死容積百分比差異無統計學意義(P=0.928),但3 mg/kg WIN 55,212-2可引起大鼠明顯嗜睡和倦怠.結論 CB受體激動劑WIN 55,212-2預處理能誘導腦缺血耐受,對大鼠局灶性腦缺血再灌注損傷具有保護作用,并具有一定的劑量相火性.

Abstract：

Objective To investigate the neuroprotective effect of preconditioning with eannabinoid (CB) receptor agonist WIN 55,212-2 on focal cerebral ischemia. Methods Fifty male SD rats were randomly assigned to 5 equal groups: control group undergoing middle cerebral artery occlusion (MCAO) for 2 h only without any preconditioning; 3 WIN 55,212-2 preconditioning groups (wiN1 -3) injected intraperitoneally with WIN 55,212-2 at the doses of 0. 3, 1, and 3 mg/kg respectively 24 h before MCAO for 2 h, and DMSO group injected intraperitoneally with dimethyl sulfoxide (DMSO), solvent of WIN 55,212-2 24 h before MCAO for 2 h. 24,48, and 72 hours after reperfusion the neurological function score (NFS) was evaluated the rats were then decapitated with their brains taken out. Brain infarct volume was evaluated with 2% 2, 3, 5-triphenyltetrazolium chloride (TTC) staining Results The NFS values of the rats in WIN 55, 212-2 preconditioning groups were all significantly higher than those of the control and DMSO groups ( all P<0. 05) while the infarct volumes of the WIN 55,212-2 preconditioning groups were all significantly smaller than those of the control and DMSO groups ( all P < 0. 05) 24, 48, and 72 h after reperfusion. The infarct volumes of the WIN2 and WIN3 groups were both significantly smaller than that of the WINI group (both P < 0. 05 ). However, there was no significant difference in the infarct volume between WIN2 and WIN3 groups (P = 0. 928). Conclusion WIN 55,212-2 preconditioning has neuroprotective effect on focal cerebral ischemia with a dose-dependent manner.

作者：	陳燁[1]CHEN Shao-yang[2]王強[1]SUN Jing[2]朱正華[1]侯立朝[1]XIONG Li-ze[2]
Author：	CHEN Ye[1]  CHEN Shao-yang[2]  WANG Qiang[1]  SUN Jing[2]  ZHU Zheng-hua[1]  HOU Li-chao[1]  XIONG Li-ze[2]
作者單位：	第四軍醫大學西京醫院麻醉科,西安,710032 Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
期 刊：	中華醫學雜志   ISTICPKU
Journal：	NATIONAL MEDICAL JOURNAL OF CHINA
年，卷(期)：	2008, 88(31)
分類號：	R74
關鍵詞：	缺血預處理    局灶性腦缺血    大鼠    大麻素受體激動劑
Keywords：	Ischemic preconditioning    Focal cerebral ischemia    Rats    Cannabinoid receptoragonist
機標分類號：	R74 R96
機標關鍵詞：	大麻素    受體激動劑    預處理    大鼠局灶性腦缺血    腦缺血再灌注損傷    保護作用    focal cerebral ischemia    neuroprotective effect    梗死容積    腹腔注射    middle cerebral artery    dimethyl sulfoxide    局灶性腦缺血模型    動脈栓塞    注射生理鹽水    神經功能評分    統計學意義    腦缺血耐受    二甲基亞砜    大鼠大腦
基金項目：	國家自然科學基金