Department of Pediatrics, Shengli Oil Field Central Hospital, Dongying, 257034, China.
World J Pediatr. 2015 Feb;11(1):74-82. doi: 10.1007/s12519-014-0531-8. Epub 2014 Dec 1.
Oxidative stress is involved in the development of hypoxic-ischemic brain damage (HIBD). In this study, we investigated the therapeutic effects of placenta-derived mesenchymal stem cells (PD-MSCs) and explored the NF-E2-related factor-2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway in treating HIBD.
P7 rats were subjected to hypoxic-ischemic brain injury and randomly divided into four groups (control, HIBD, HIBD+PD-MSCs, and HIBD+fibroblasts). Forty-eight hours after the induction of HIBD, 5×10(5) of PD-MSCs were injected into cerebral tissue in the HIBD+PD-MSCs group, while the same dose of fibroblasts were injected in the HIBD+fibroblasts group. Morris Water Maze, gross and pathological changes were tested at P28. The level of malondialdehyde (MDA) was detected in rats' hippocampus. RT-PCR and western blot analysis were used to evaluate the changes of Nrf2/HO-1.
The HIBD group showed significantly longer escape latency and a lower frequency of original platform crossing in the Morris Water Maze compared with the control group. Rats receiving PD-MSCs showed significant improvement of HIBD. The pathological changes were evident after HIBD, but ameliorated in the PD-MSCs group. Compared with the control group, HO-1 and Nrf2 were up-regulated at gene and protein levels in the HI brain, beginning at 6 hours and peaking at 48 hours (P<0.05). The expression of HO-1 and Nrf2 in the PD-MSCs treatment group was more pronounced than in the HIBD group (P<0.01). PD-MSCs also decreased MDA production in the brain tissue.
These results demonstrate that PD-MSCs have neuroprotective effect during the treatment of HIBD and that the mechanism may be partly due to alleviating oxidative stress.
氧化应激参与了缺氧缺血性脑损伤（HIBD）的发生发展。在这项研究中，我们研究了胎盘来源间充质干细胞（PD-MSCs）的治疗效果，并探讨了 NF-E2 相关因子 2/血红素加氧酶-1（Nrf2/HO-1）信号通路在治疗 HIBD 中的作用。
将 P7 大鼠制成缺氧缺血性脑损伤模型，随机分为四组（对照组、HIBD 组、HIBD+PD-MSCs 组和 HIBD+成纤维细胞组）。HIBD 诱导 48 小时后，将 5×10(5)个 PD-MSCs 注入 HIBD+PD-MSCs 组的脑组织中，同时将相同剂量的成纤维细胞注入 HIBD+成纤维细胞组。在 P28 时，通过 Morris 水迷宫、大体和组织病理学改变进行测试。检测大鼠海马组织丙二醛（MDA）的水平。通过 RT-PCR 和 Western blot 分析评估 Nrf2/HO-1 的变化。
与对照组相比，HIBD 组大鼠在 Morris 水迷宫中的逃避潜伏期明显延长，原平台穿越次数明显减少。接受 PD-MSCs 治疗的大鼠 HIBD 明显改善。HIBD 后可见明显的病理变化，而在 PD-MSCs 组则有所改善。与对照组相比，HI 大脑中 HO-1 和 Nrf2 的基因和蛋白水平在 6 小时开始上调，在 48 小时达到高峰（P<0.05）。PD-MSCs 治疗组的 HO-1 和 Nrf2 表达明显强于 HIBD 组（P<0.01）。PD-MSCs 还减少了脑组织中 MDA 的产生。
这些结果表明，PD-MSCs 在治疗 HIBD 中具有神经保护作用，其机制部分可能是通过减轻氧化应激。
