摘要
目的:探讨重组人促红细胞生成素(rh-EPO)对缺氧缺血性脑损伤(HIBD)海马神经细胞凋亡及学习、记忆能力的保护作用。方法:将7日龄SD大鼠分成HIBD模型组(n=11)、rh-EPO治疗组(n=11)、假手术对照组(n=10)。用电镜观察缺氧缺血后24h三组海马神经细胞凋亡特征;比较缺氧缺血后0、6、12、24h模型组和治疗组动物自发左旋、夹尾左旋、夹尾尖叫发生率;利用跳台试验观察三组大鼠生后75天学习、记忆潜伏期和错误次数。结果:与对照组相比,模型组电镜观察结果显示大量海马神经细胞凋亡,治疗组较模型组凋亡细胞明显减少。缺氧后0h,两组动物均出现自发左旋、夹尾左旋、夹尾尖叫现象(治疗组10/10,模型组9/9),缺氧后24h治疗组与模型组比较,上述现象发生率明显降低(治疗组1/10、模型组6/9,P=0.0198)。跳台试验发现模型组动物学习、记忆能力受损;学习潜伏期与对照组相比明显延长,错误次数明显增多(P均<0.01),记忆潜伏期与对照组比较明显缩短,错误次数显著增加(P均<0.01),治疗组动物学习、记忆能力均较模型组明显改善(P<0.01),与对照组比较均无显著性差异(P>O.05)。结论:rh-EPO可抑制HIBD神经细胞凋亡,减轻脑损伤,改善动物学习、记忆能力;rh-EPO有望成为新生儿缺氧缺血性脑病一种新的治疗方法。
Objective: To investigate the protective effects of erythropoietin on nerve apoptosis in hippocampus and the ability of learning and memory impaired by hypoxia-ischemia brain damage(HIBD). Methods:Seven days old Sprague-Dawley rats were divided into hypoxia-isehemia (HI) group(n = 11), recombinant human etythropoietin (rh-EPO) treated group(n = 11), and sham-oper ated control group (n = 10). The apoptotic characteristics were observed in the three groups by electron microscope 24 h after hypoxia. The number of rats with spontaneous left-turn, nip-tail left-turn, nip-tail squeal in HI group and rh-EPO treated group was counted respectively 0,6, 12 and 24 h after hypoxia-ischemia,respectively. Step down test was used to determine escape latency (EL),step down latency (SDL) and both error times of learning and memory in three groups at 75-day old. Results: Two rats in HI group and one in rh-EPO treated group died from continuous convulsion during hypoxia. In HI group, a large number of apoptosis nerve cells were observed, which was reduced in rh-EPO treated group. All rats in the two groups had spontaneous left-turn, nip-tail left-turn, nip-tail squeal at the time of hypoxia (rh-EPO treated group vs HI group, 10/10 vs 9/9). Compared with HI group, the rate of sponta ncous left-turn was dramatically lower in rh-EPO treated group (rh-EPO treated group vs HI group, 1/10 vs 6/9,P = 0.0198). Compared with control group, EL of HI group was longer (P 〈 0.01 ), SDL was shorter (P 〈 0.01 ), both error times of tearuing and memory were more. These abnormalities are corrected in rh-EPO treated group (P 〈 0.01 ), and were not different with those in control group (P 〉 0.057. Conclusion: rh-EPO can inhibit nerve cell apoptosis induced by HI, alleviate brain scathe, and improve the ability of learning and memory. Rh-EPO might become a new drug to treat hypoxic-ischemic encephalopathy in newborns.
出处
《南京医科大学学报(自然科学版)》
CAS
CSCD
北大核心
2006年第10期937-940,共4页
Journal of Nanjing Medical University(Natural Sciences)