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目的 研究L-精氨酸/一氧化氮(NO)信号通路在氯胺酮抗抑郁中的作用.方法 雄性Wistar大鼠42只,200～250g,随机数字表法分为7组(n=6):对照组(C组)、L-精氨酸(NO合成前体物质)组(LA组)、L-NAME[非特异性一氧化氮合酶(NOS)抑制剂]组(LN组)、氯胺酮3.0 mg/kg组(K3组)、氯胺酮10 mg/kg组(K10组)、L-精氨酸+氯胺酮10.0 mg/kg组(LAK10组)、L-NAME+氯胺酮3.0 mg/kg组(LNK3组).强迫游泳15 min建立大鼠抑郁模型(前游泳),24h后再次强迫游泳实验6min(测试游泳),记录后5 min不动时间.在测试游泳前90 min各组大鼠分别给予生理盐水1.0ml、L-精氨酸75 mg/kg或L-NAME 30 mg/kg预处理.在测试游泳前60 min分别给予生理盐水1.0ml、氯胺酮3.0 mg/kg或氯胺酮10.0 mg/kg治疗.行为学测试结束后,取大鼠海马组织测定NO含量.结果 与C组相比[不动时间:(139.0±27.6)s],K10组、LNK3组不动时间明显下降[(85.5 ±34.2)s,(91.3 ±31.6)s] (P＜0.05),K3组、LA组、LAK10组、LN组未见显著差异(P＞0.05)；与C组相比[(0.61 ±0.21) μmol/gProt],LA组显著上升[( 1.09 ±0.39) μmol/gProt] (P＜ 0.05),K10组、LNK3组NO含量显著下降[(0.28±0.12) μmol/gProt,(0.31±0.14) μmol/gProt](P＜0.05),K3组、LAK10组、LN组间差异无统计学意义(P＞0.05).结论 氯胺酮的抗抑郁作用与海马L-精氨酸/一氧化氮信号通路抑制有关.“,”Objective To study the role of L-arginine/nitric oxide (NO) pathway in the antidepressant effects of ketamine.Methods Forty two male Wistar rats (200-250 g) were equally randomized into 7 groups ( n =6 ):control group ( C group ),L-Arginine ( a precursor of NO ) group ( LA group),L-NAME ( an non-selectivity inhibitor of NO synthase) group ( LN group),ketamine 3 mg/kg group ( K3 group),ketamine 10 mg/kg group (K10 group),L-Arginine + ketamine 10 mg/kg group(LAK10 group),L-NAME + ketamine 3 mg/kg group (LNK3 group).The forced swimming test (FST) of 15 min (pre-test session) was used to establish a rat depression model,then twenty-four hours later FST (test session) was carried out of 6 min and the immobility time in last 5 min was recorded. All the groups were pretreated with saline 1.0 ml,L-arginine 750 mg/kg or L-NAME 30 mg/kg 90 min before FST.Saline 1.0 ml,ketamine 3.0 mg/kg or ketamine 10.0 mg/kg were injected 60 min before FST.The content of hippocampal NO was detected immediately after ethology measurement.Results Compared with C group (immobility time:( 139.0 ± 27.6)s),the immobility time decreased significantly (( 85.5 ± 34.2),(91.3 ±31.6)s) in K10 group and LNK3 group (P＜0.05),K3 group,LA group,LAK10 group and LN group had no significant difference (P＞0.05) ;compared with C group ( (0.61 ±0.21 ) μmol/gProt),the content of NO increased in LA group ( ( 1.09 ±0.39) μmol/gProt) and decreased in K10 group and LNK3 group significantly( (0.28 ± 0.12),(0.31 ± 0.14 ) μmol/gProt) (P ＜ 0.05 ),K3 group,LAK10 group and LN group had no significant difference (P ＞ 0.05).Conclusion The antidepressant effects of ketamine are related to the suppression of L-arginine/nitric oxide pathway.