目的 研究利多卡因对海马的神经毒性是否会对大鼠空间学习记忆能力产生影响，并探讨大鼠空间学习能力的变化与海马CA3区锥体细胞数目的相关性。 方法 将成年Wistar雄性大鼠随机分为基础值组（n=7）和利多卡因惊厥组（n=40）。基础值组大鼠静脉给予生理盐水后使用Y迷宫测定大鼠的空间学习能力。利多卡因惊厥组大鼠尾静脉持续输注利多卡因造成惊厥，待大鼠恢复正常运动以后放入鼠笼重新饲养。并于惊厥后第1、3、5、7天从中随机抓取大鼠测试其空间学习能力以及组织学改变。根据对应天数将利多卡因惊厥组的40只大鼠随机细分为Day-1、Day-3、Day-5、Day-7亚组，每亚组10只。所有大鼠在测定空间学习能力之后立即处死，取出大脑并做石蜡包埋，冠状面切片后进行组织学检测，显微镜下评估海马CA3区锥体细胞状态。 结果 ① 基础值组和Day-1、Day-3、Day-5、Day-7亚组大鼠的Y迷宫穿梭次数分别为（25.2 ± 3.7）、（27.1 ± 8.1）、（36.9 ± 9.9）、（38.7 ± 10.6）、（40.6 ± 16.3）次，除Day-1亚组与基础值组比较差异无统计学意义（P＞0.05）外，其余各亚组与基础值组差异均有统计学意义（P＜0.05）；② 与基础值组单位面积（10.3 ± 4.5）个（异常锥体）细胞比较，利多卡因惊厥组大鼠海马CA3区异常锥体细胞数增加，Day-1、Day-3、Day-5、Day-7亚组计数值分别为13.0 ± 7.2、15.6 ± 5.0、19.6 ± 8.1、18.1 ± 5.1，且与大鼠Y迷宫穿梭次数呈正相关（r=0.711，P＜0.05）。 结论 利多卡因引起的惊厥使成年大鼠海马依赖性空间学习能力下降，利多卡因的神经毒性引起的海马异常锥体细胞增多可能是造成这一现象的一种原因。
Objective Isoflurane has an acute preconditioning effectiveness against ischemia in kidney, but this beneficial effectiveness can only last for 2-3 hours. To investigate whether isoflurane produces delayed preconditioningagainst renal ischemia/reperfusion (I/R) injury, and whether this process is mediated by hypoxia inducible factor 1α(HIF- 1α). Methods A total of 52 male C57BL/6 mice were randomly assigned to 4 groups (n=13 in each group): the controlgroup (group A), PBS/isoflurane treated group (group B), scrambled small interference RNA (siRNA)/isoflurane treated group (group C), and HIF-1α siRNA/isoflurane treated group (group D). In groups C and D, 1 mL RNase-free PBS containing 50 μg scrambled siRNA or HIF-1α siRNA was administered via tail vein 24 hours before gas exposure, respectively. Equivalent RNasefree PBS was given in groups A and B. Then the mice in groups B, C, and D were exposed to 1.5% isoflurne and 25%O2 for 2 hours; while the mice in group A received 25%O2 for 2 hours. After 24 hours, 5 mice in each group were sacrificed to assesse the expressions of HIF-1α and erythropoietin (EPO) in renal cortex by Western blot. Renal I/R injury was induced with bilateral renal pedicle occlusion for 25 minutes followed by 24 hours reperfusion on the other 8 mice. At the end of reperfusion, the serum creatinine (SCr), the blood urea nitrogen (BUN), and the histological grading were measured. Results The expressions of HIF-1α and EPO in groups B and C were significantly higher than those in group A (P lt; 0.01). The concentrations of SCr and BUN in groups B and C were significantly lower than those in group A, as well as the scores of tubules (P lt; 0.01), and the injury of kidney was amel iorated noticeably in groups B and C. The expressions of HIF-1α and the concentrations of SCr and BUN in group D were significantly lower than those in group A (P lt; 0.01). Compared with groups B and C, the expression of HIF- 1α and EPO in group D decreased markedly (P lt; 0.01), the concentrations of SCr and BUN were increased obviously, as well asthe scores of tubules (P lt; 0.01), and the renal injury was aggratived significantly. Conclusion Isoflurane produces delayed preconditioning against renal I/R injury, and this beneficial effectiveness may be mediated by HIF-1α.