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目的探讨铁离子螯合剂(DFO)对缺氧缺血性脑损伤(HIBD)新生大鼠缺氧诱导因子1α(HIF-1α)的调节作用及机制。方法以10日龄SD大鼠48只为研究对象,分为假手术组、缺氧缺血(HI)组、DFO干预组和9 g.L-1盐水对照组,每组分为缺氧后4 h、8 h及24 h 3个亚组,参照Rice模型制作HIBD动物模型,并经腹腔内注射DFO及9 g.L-1盐水干预。应用Western blot法检测分析其HIF-1α、Akt及p-Akt蛋白表达。RT-PCR检测分析HIF-1αmRNA表达。结果 HI组HIF-1α蛋白4 h即明显增多,8 h达高峰,24 h开始下降,9 g.L-1盐水对照组与HI组有相同变化。而DFO干预组4 h达高峰,8 h及24 h仍在较高水平,与HI组比较各时间点HIF-1α蛋白表达均增多,差异均有统计学意义(Pa<0.05)。DFO干预组和HI组各时间点HIF-1α蛋白表达与假手术组比较均增高(Pa<0.05)。HI组与DFO干预组各时间点Akt蛋白表达无明显差异(P>0.05),2组p-Akt蛋白表达有相同趋势,缺氧4 h HI组与DFO干预组p-Akt蛋白表达无显著性差异。然而与HI组比较,DFO组HIF-1αmRNA表达均有增加。结论在新生鼠HIBD时,DFO可上调HIF-1α蛋白及mRNA表达,使HIF-1α蛋白表达高峰时间提前,且持续时间延长,在此过程中PI3K/Akt信号通路未参与DFO对HIF-1α的调节。
Objective To investigate the regulatory effect and mechanism of iron ion chelator (DFO) on hypoxia inducible factor 1α (HIF-1α) in neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods 48 Sprague-Dawley (SD) rats of 10 days old were divided into four groups: sham operation group, HI group, DFO intervention group and 9 gL-1 saline control group. , 8 h and 24 h respectively. The HIBD animal models were made according to the model of Rice, and then intraperitoneally injected with DFO and 9 g L-1 saline. The protein expression of HIF-1α, Akt and p-Akt was detected by Western blot. HIF-1α mRNA expression was analyzed by RT-PCR. Results HIF-1αprotein in HI group increased significantly at 4 h, peaked at 8 h, decreased at 24 h, and changed at 9 g.L-1 in saline control group and HI group. However, DFO intervention group reached the peak at 4 h, and remained high at 8 h and 24 h. Compared with HI group, the expression of HIF-1α protein increased at each time point (P <0.05). The expression of HIF-1α in DFO intervention group and HI group at each time point was significantly higher than that in sham operation group (P <0.05). There was no significant difference in Akt protein expression between HI group and DFO intervention group at each time point (P> 0.05). The expression of p-Akt protein in the two groups had the same trend, while the expression of p-Akt protein in HI group and DFO group had no significant difference difference. However, compared with HI group, the expression of HIF-1αmRNA increased in DFO group. Conclusions DFO can up-regulate the expression of HIF-1α protein and mRNA in HIBD neonatal rats, and lead to the peak of HIF-1α protein expression and prolongation of duration. During this process, the PI3K / Akt signaling pathway is not involved in the effect of DFO on HIF-1α adjust.