雌激素通过NMDA受体NR2B亚基对艾司氯胺酮麻醉的影响

Effect of estrogen on esketamine anesthetic via NR2B/N-methyl-D-aspartate receptor

目的探讨雌激素通过NMDA受体NR2B亚基对艾司氯胺酮麻醉效能的影响。方法40只雌性SD大鼠,体重200~250 g,8周龄,采用随机数字表法分为4组(每组10只):对照组(C组)、卵巢切除组(OVX组)、雌激素替代治疗组(E组)和雌激素联合NR2B拮抗剂Ro25-6981组(ERo组)。OVX组、E组和ERo组行双侧卵巢切除术,C组只打开腹腔找到卵巢不切除。E组和ERo组大鼠分别于卵巢切除术后腹腔注射雌激素或雌激素联合Ro25-6981连续7 d,C组和OVX组注射等量生理盐水。于第7天药物注射1 h后行艾司氯胺酮(50 mg/kg)腹腔注射麻醉。记录大鼠翻正反射消失(loss of righting reflex,LRR)开始时间和持续时间,LRR测定结束后检测血清雌激素水平。结果与C组比较,OVX组和E+Ro组LRR开始时间增长(P<0.05),而LRR持续时间缩短(P<0.05);E组LRR开始时间有所增长,LRR持续时间稍微缩短,但差异无统计学意义(P>0.05)。与OVX组比较,E组LRR开始时间缩短(P<0.05),LRR持续时间增长(P<0.05);E+Ro组LRR开始时间缩短(P<0.05),但LRR持续时间差异无统计学意义(P>0.05)。与E组比较,E+Ro组LRR开始时间增长(P<0.05),LRR持续时间缩短(P<0.05)。与C组比较,OVX组、E组、E+Ro组大鼠血清雌激素水平均明显下降(P<0.05);与OVX组比较,E组和E+Ro组大鼠血清雌激素水平均升高(P<0.05);E+Ro组与E组比较雌激素水平有所下降(P<0.05)。结论雌激素通过NMDA受体NR2B亚基增强了艾司氯胺酮的麻醉效能。

Objective To investigate the effect of estrogen on esktamine anesthetic efficacy through regulating the NR2B subgroup of N-methyl-D-aspartate(NMDA)receptor.Methods According to the random number table method,40 Sprague-Dawley female rats,weighing 200-250 g,aged 8 weeks,were divided into four groups(n=10):a control group(group C),an ovariectomy group(group OVX),a 17β-estradiol treatment group(group E)and a 17β-estradiol combined with the NR2B/NMDA receptor antagonist Ro25-6981 group(group ERo).Rats in OVX group,E group and ERo group were ovariectomized,while rats in C group were received sham operation.Rats in groups E and ERo were intraperitoneally injected with 17β-estradiol or 17β-estradiol combined with Ro25-6981 for consecutive seven days after ovariectomy,respectively.Groups C and OVX were injected with the equal volume of normal saline.Esktamine anesthesia(50 mg/kg)was performed 1 h after the administration on day 7.The onset and duration of the loss of righting reflex(LRR)were recorded.The levels of 17β-estradiol in the serum were determined after LRR tests.Results Compared with group C,the onset of LRR increased,the duration of LRR decreased in group OVX and group E+Ro(P<0.05);the onset of LRR increased and the duration of LRR decreased in group E,but the difference was not statistically significant(P>0.05).Compared with OVX group,the onset of LRR decreased,the duration of LRR increased in group E(P<0.05);the onset of LRR decreased(P<0.05),but the duration of LRR was not significantly different in group E+Ro(P>0.05).Compared with group E,the onset of LRR increased,and the duration of LRR decreased in group E+Ro(P<0.05).Compared with group C,the level of serum estrogen significantly decreased in group OVX,group E and group E+Ro(P<0.05);compared with group OVX,the level of serum estrogen increased in group E and group E+Ro(P<0.05);Compared with group E,the level of serum estrogen decreased in group E+Ro(P<0.05).Conclusion Estrogen enhances esktamine anesthetic efficacy via NR2B/NMDA receptor.