脑白质损伤新生大鼠核转录因子-κB和诱导型一氧化氮合酶表达的变化

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目的研究缺氧缺血(HI)对新生大鼠脑白质胶质细胞核转录因子κB(NF-κB)及诱导型一氧化氮合酶(iNOS)表达的影响,探讨NF-κB及iNOS在新生大鼠脑白质损伤(WMD)发病机制中的作用。方法将2日龄大鼠随机分为实验组和假手术组,建立新生大鼠WMD模型,分别于HI后1 h、3 h、6 h、12 h、1 d、3 d及7 d处死,对其脑组织取材后行HE染色观察其病理改变,并应用免疫组织化学法检测其NF-κB及iNOS的表达水平。结果在新生大鼠脑白质中,实验组NF-κB表达水平于HI后1 h开始明显上升,12 h达到高峰,至7 d仍明显升高,与对照组比较差异均有统计学意义[(45.2±2.5)vs(35.7±2.1);(62.3±2.9)vs(34.1±2.0);(75.0±3.7)vs(33.6±2.1);(126.2±4.3)vs(14.3±2.4);(81.1±2.6)vs(33.7±2.0);(40.2±2.5)vs(32.5±2.3);(34.6±2.6)vs(31.9±2.8),Pa<0.001]。实验组iNOS于HI后1 h表达开始显著增多,1 d达到高峰,至7 d仍明显升高,与对照组比较差异均有统计学意义[(25.4±1.7)vs(22.7±1.9);(37.9±1.9)vs(21.7±1.2);(53.3±2.1)vs(21.9±1.0);(61.9±1.7)vs(21.7±1.3);(74.0±2.2)vs(22.7±1.5);(57.3±2.2)vs(21.1±1.1);(26.3±2.5)vs(20.8±1.6),Pa<0.001]。实验组脑室周围白质区NF-κB表达与iNOS呈正相关(r=0.977,P<0.001)。结论 HI可导致新生大鼠脑白质NF-κB表达及iNOS水平显著增高,参与新生大鼠WMD的病理生理过程。 Objective To investigate the effects of hypoxia-ischemia (HI) on the expression of NF-κB and iNOS in neonatal rats with neuratropoietic glia and to explore the role of NF-κB and iNOS in neonatal rats The role of brain white matter damage (WMD) in pathogenesis. Methods The 2-day-old rats were randomly divided into experimental group and sham operation group. The WMD model of neonatal rats was established. The rats were sacrificed at 1, 3, 6, 12, 1, 3 and 7 days after HI, The brain tissues were harvested and stained with hematoxylin-eosin (HE) to observe the pathological changes. The expression of NF-κB and iNOS was detected by immunohistochemistry. Results In neonatal rats, the expression of NF-κB in experimental group began to increase at 1 h after HI and peaked at 12 h, and still increased significantly at 7 d, which was significantly different from that in control group [( 45.2 ± 2.5 vs 35.7 ± 2.1; 62.3 ± 2.9 vs 34.1 ± 2.0; (75.0 ± 3.7) vs (33.6 ± 2.1); (126.2 ± 4.3) vs (14.3 ± 2.4); (81.1 ± 2.6) vs (33.7 ± 2.0); (40.2 ± 2.5) vs (32.5 ± 2.3); (34.6 ± 2.6) vs (31.9 ± 2.8), Pa <0.001]. The expression of iNOS in experimental group began to increase significantly at 1 h after HI, reaching the peak at 1 d and still increasing significantly at 7 d, which was significantly different from that in control group [(25.4 ± 1.7) vs (22.7 ± 1.9); ( 37.9 ± 1.9 vs 21.7 ± 1.2; and (53.3 ± 2.1) vs (21.9 ± 1.0); (61.9 ± 1.7) vs (21.7 ± 1.3); (74.0 ± 2.2) vs (22.7 ± 1.5); (57.3 ± 2.2) vs (21.1 ± 1.1); (26.3 ± 2.5) vs (20.8 ± 1.6), Pa <0.001]. The periventricular white matter NF-κB expression in the experimental group was positively correlated with iNOS (r = 0.977, P <0.001). Conclusion HI can induce the expression of NF-κB and iNOS in the white matter of neonatal rats, which is involved in the pathophysiological process of WMD in neonatal rats.
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