XIAP过度表达对未成熟脑急性放射损伤后脑组织硝基酪氨酸和4-羟基壬烯醛表达的影响

Effects of X-linked inhibitor of apoptosis(XIAP) protein on nitrotyrosine and 4-hydroxy-2-noneal formation following irradiation exposure in the developing brain

目的探讨急性放射损伤对未成熟脑高增殖细胞的影响以及X-染色体连锁的凋亡抑制剂(XIAP)过度表达对放射后氧化应激产物硝基酪氨酸(NT)和4-羟基壬烯醛(4-HNE)形成的影响。方法新生10日龄XIAP过度表达转基因C57BL/6小鼠(XIAP组)及同期野生型10日龄C57BL/6小鼠在8Gy单一剂量放射线照射后6h或7d处死取脑,进行脑组织硝基酪氨酸和4-羟基壬烯醛免疫组化染色,以及海马齿状回、侧脑室下区面积测量。结果照射后7d海马齿状回、侧脑室下区面积较对照组明显下降,照射后脑组织硝基酪氨酸和4-羟基壬烯醛免疫活性明显增加,照射后6hXIAP过度表达组大脑海马齿状回、侧脑室下区硝基酪氨酸和4-HNE的阳性细胞数明显低于野生组(P<0.05,P<0.001)。结论放射线照射可导致活性氧、活性氮基团过度表达,进而引起高增殖细胞损伤;XIAP过度表达可能抑制照射后硝基酪氨酸和4-HNE的形成。

Objective To investigate the effect of acute irradiation injury on highly proliferating cells and the relation between XIAP overexpression and formation of free radicals. Methods One hemisphere of postnatal day 10 wide type or XIAP over expression mice were irradiated with a single dose of 8 Gy, and animals were sacrificed at 6h or 7d after irradiation （IR）. Immunoreactivities of nitrotyrosine （NT） and 4-hydroxy-2-noneal （HNE） were detected in the subventricular zone （SVZ） and the granular cell layer （GCL） of the dentate gyrus at 6h post-IR by immnohistochemistry. The area in dentate gyrus （GCL ＋ SGZ） and SVZ was calculated at 7d post-IR. Results The SVZ and dentate gyrus areas decreased greatly at 7d after IR. Nitrotyrosine or 4-hydroxy-2-noneal immunoreactivity increased greatly after IR. Overexpression of XIAP inhibited nitrotyrosine and 4-hydroxy-2-noneal formation in both GCL and SVZ. Conclusion Based on these findings, it indicates that irradiation injury can cause reactive oxygen species（ROS） and reactive nitrogen species（RNS） formation ,which contributes to highly proliferating calls damage. Overexpression of X-linked inhibitor of apoptosis protein reduces the formation of RNS/ROS.