促红细胞生成素对缺氧缺血性脑损伤大鼠的脑保护作用及机制

发布时间：2018-08-16 17:53

【摘要】：目的观察促红细胞生成素(EPO)对缺氧缺血性脑损伤(HIBD)大鼠的脑保护作用并探讨其机制。方法选取7日龄Wistar新生大鼠120只,随机分为假手术组(对照组)、HIBD组、EPO治疗组各40只。EPO治疗组在HIBD模型建立后按5 000 IU/kg的剂量腹腔注射EPO,HIBD组注射等体积生理盐水。各组分别在6、12、24、48、72 h各处死8只大鼠,分别采用Real-time PCR法、Western blotting法检测脑组织中Fas及Fas L mRNA、蛋白表达。结果 HIBD组Fas mRNA在6 h后开始上升,12 h达最大值,24 h后开始下降,EPO治疗组在对应时间点Fas mRNA的相对表达量均低于HIBD组,且在12、24、48 h三个时点两组间的差别有统计学意义(P均0.05);Fas L mRNA相对表达量在6~24 h显著上升且在第24小时达最大值,之后开始下降,EPO治疗组Fas L mRNA水平在6、12、24、48 h均显著低于HIBD组(P均0.05)。对照组Fas和Fas L蛋白维持在较低的基础水平,HIBD组Fas及Fas L蛋白均有一个先升后降的明显变化趋势,EPO治疗组Fas及Fas L蛋白表达明显减少,Fas蛋白在24、48 h及Fas L蛋白在所有时点与HIBD组比较,P均0.05。结论 EPO能明显减缓HIBD对脑组织神经元的伤害,起到有效保护作用;其机制可能是通过下调HIBD脑组织中的Fas/Fas L信号通路,抑制神经元细胞的凋亡。
[Abstract]:Objective To observe the protective effect of erythropoietin (EPO) on hypoxic-ischemic brain damage (HIBD) in rats and explore its mechanism.Methods 120 7-day-old Wistar neonatal rats were randomly divided into sham operation group (control group), HIBD group and EPO treatment group (40 rats in each group). Eight rats in each group were sacrificed at 6,12,24,48 and 72 hours respectively. Fas and Fas L mRNA and protein expression in brain tissues were detected by Real-time PCR and Western blotting respectively. Results Fas mRNA in HIBD group began to increase after 6 hours, reached the maximum at 12 hours, and began to decrease after 24 hours. Fas mRNA expression in EPO group began to increase at the corresponding time points. The relative expression of Fas L mRNA in EPO group was significantly lower than that in HIBD group at 12,24 and 48 hours (P 0.05); Fas L mRNA increased significantly at 6-24 hours and reached its maximum at 24 hours, then began to decline. Fas L mRNA levels in EPO group were significantly lower than that in HIBD group at 6,12,24 and 48 hours (P 0.05). The expression of Fas and Fas L protein in EPO treatment group was significantly decreased. Fas protein in 24,48 hours and Fas L protein in all time points were compared with that in HIBD group, P were 0.05. Conclusion EPO can significantly reduce the injury of HIBD to brain neurons. The mechanism may be through down-regulation of Fas/Fas L signaling pathway in HIBD brain tissue to inhibit neuronal apoptosis.
【作者单位】：河北医科大学第一医院;定州市妇幼保健院;
【基金】：河北省医学科学研究重点课题计划项目(ZD20140096)
【分类号】：R714.7

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