促红细胞生成素对新生鼠缺氧缺血性脑损伤海马CA1区Caspase-3激活的影响

Effects of Erythropoietin on Activation of Cas pase-3 in Newborn Rat Hippocampal CA1 Region Pest Hypoxic-ischemic Brain Damage

目的 探讨重组人促红细胞生成素 (rhEPO )对新生鼠缺氧缺血性脑损伤 (HIBD)的保护作用及对海马CA1区Caspase 3激活的影响。 方法 将 7日龄SD大鼠分为缺氧缺血模型组 (n= 11)、rhEPO治疗组 (n =11)和假手术对照组 (n =10 ) ,模型组和治疗组建立新生鼠缺氧缺血性脑损伤模型。观察模型组和治疗组缺氧后 0、6、12、2 4h不同时间点自发左旋、夹尾左旋、夹尾尖叫现象。用免疫组织化学方法检测活化的Caspase 3的表达 ,观察Caspase 3阳性细胞在脑组织内分布情况 ,计算各组海马CA1区单位面积内阳性细胞数 (个 / 1mm)。 结果 模型组 2只、治疗组 1只在缺氧过程中因持续抽搐死亡。缺氧后 0h两组动物均出现自发左旋 (治疗组 10 / 10 ,模型组 9/ 9) ,2 4h治疗组自发左旋发生率明显减少 (治疗组 1/ 10 ,模型组 6/ 9,P =0 .0 198)。免疫组化显示Caspase 3阳性细胞在对照组脑组织内散在分布 ,模型组和治疗组在海马、大脑皮层较为密集。模型组CA1区阳性细胞数显著高于对照组 (41.3 8± 2 .0 9vs 10 .52± 2 .70 ,P <0 .0 1)。治疗组阳性细胞数显著低于模型组(41.3 8± 2 .0 9vs 2 2 .63± 3 .17,P <0 .0 1)。 结论 Caspase 3在新生鼠HIBD中活性显著增高 ,应用rhEPO能有效抑制Caspase 3激活 。

ObjectiveTo investigate the effects of erythro po ietin on prevention hypoxic-ischemic brain damage (HIBD) and activation of Casp ase-3 in Hippocampal CA1 region in newborn rats. Methods7 d Sprague-Dawley rats were divided into hypoxic-ischemic (HI) group (n=11), recombinant human erythropoietin (rhEPO) treated group (n=11), and sham-op erated control group (n=9). HIBD was established in both HI group and rhEPO treated group. The number of rats animals with spontaneous left-turn in two gro ups was counted respectively at subsequent different time: 0, 6, 12 and 24 h. Th e expression and distribution of activated Caspase-3 was detected by immunohist ochemistry analysis. The positive cells were calculated in hippocampal CA1 regio n of every groups.ResultsTwo rats in HI group and one in rhE PO treated group died from continuous convulsion during hypoxia. all survival ra ts in up two groups had spontaneously left-turn Compared with HI group, the r ate of spontaneous left-turn was dramatically lower in rhEPO treated group (HI group vs rhEPO treated group, 1/10 vs 6/9, P=0.0198) at 24 h after hypox ia. The positive stained cells were distributed dispersively in the brain of con trol group, and more intensively in the hippocampus and cerebral cortex of the o ther two groups. In CA1 region, the number of positive cells in HI group, was si gnificant higher than that in control group ( 41.38 ±2.09 vs 10.52±2.70 , P<0.01) and rhEPO treated group (41.38 ±2.09 vs 22.63±3.17, P <0.01). ConclusionrhEPO might alleviate the HIBD in newbor n rats though inhibiting the activation of Caspase-3, and it might become a pro mising drug used in clinic treatment to hypoxic-ischemic encephalopathy.