锂剂抑制新生鼠缺氧缺血后的细胞凋亡及炎症反应研究

Effect of lithium on neonatal rat hypoxia-ischemia and the associated mechanism

目的探讨锂对新生鼠缺氧缺血后的神经保护作用及相关机制。方法 40只9日龄Wistar雄性大鼠建立缺氧缺血动物模型,术后给予相同剂量的氯化锂或生理盐水干预,缺氧缺血后3d灌注取脑,MAP-2免疫组化染色评估脑损伤体积,Caspase-3检测细胞凋亡,Iba-1,Galectin-3检测神经炎症反应。结果缺氧缺血后3d,锂盐治疗组脑组织脑损伤体积较对照组明显减少(P<0.01);生理盐水组动物大脑皮质Caspases-3阳性细胞数目为(32.5±5.37)个,而锂盐治疗组则为(17.3±4.46)个(P<0.01),锂盐治疗后海马DG区Caspase-3阳性细胞数目仅为对照组的约1/4(P<0.001);Iba1染色,生理盐水组动物皮层及海马DG区Iba1阳性细胞数目分别为112.6±10.72和342.5±9.67,均显著高于锂盐治疗组(皮层72.4±7.33,海马DG区224.6±9.34)(P<0.01,P<0.01);Galectin-3染色,锂盐治疗后,实验动物大脑皮质及海马DG区Galectin-3阳性细胞数目均明显少于生理盐水组(P<0.05,P<0.01)。结论锂对新生鼠缺氧缺血具有显著的神经保护作用,其机制可能为减少细胞凋亡或抑制缺氧缺血后的神经炎症。

Objective To investigate the effect of lithium on neonatal rat hypoxia-ischemia and the associated mecha- nism. Methods Forty nine-day-old male rats were subjected to unilateral hypoxia-ischemia （HI）, followed by lithium chloride or saline injection. Pups were sacrificed 3 days after HI. MAP-2 immunostaining was performed to evaluate the brain injury. Caspase-3 was used to test the apoptosis, and Iba-1, Galectin-3 were used to reflect the neural inflammation. Results Lithium reduced the total brain loss 3 days after HI （P^0.01）. The number of Caspases-3 positive cell in cortex was 32.5~ 5.37 in sa- line group, which was significantly higher than that in lithium-treated group （17.3-4-4.46, P＇~0.01）. In hippocampal DG, Caspases-3 positive cell in lithium group was reduced to 1/4 compared with saline group （P%0. 001）. IbM staining demonstra- ted that Ibal positive cell in cortex and hippocampal DG of saline group was 112.6-7 10.72 and 342.5 ~ 9.67, respectively, both of which were much higher than that in lithium group （72.4~7.33 and 224.6_--＋-9.34, respectively; P^0.01）. Galectin- 3 staining revealed the similar results between two groups （P%0.05 for cortex; P%0.01 for hippocampal DG）. Conclusion either by reducing apoptosis or by suppressing neural in