高迁移率族蛋白B1在高氧致支气管肺发育不良的表达

Expression of high mobility group protein-B1 in mice with hyperoxia-induced bronchopulmonary dysplasia

摘要:

目的：检测高迁移率族蛋白B1（HMGB1）在高浓度氧（60% O2）暴露新生小鼠肺组织损伤模型中的表达水平，探讨HMGB1在支气管肺发育不良（BPD）发病机制中的作用。方法：新生足月C57BL/6小鼠随机分为BPD组和对照组，制备高氧浓度致新生鼠BPD模型，应用苏木精-伊红染色、Masson染色、放射性肺泡计数（RAC）、免疫荧光和实时荧光定量PCR技术，观察氧暴露后3 d、7 d、14 d肺组织病理改变及HMGB1的蛋白和mRNA表达水平。结果：BPD组在氧暴露后随时间推移，出现肺泡上皮肿胀，肺泡壁增厚，间质水肿，炎症细胞浸润，胶原样物质产生，肺泡结构紊乱，数量减少，较空白对照组明显发育迟滞。在氧暴露后7 d、14 d，HMGB1及其mRNA表达均强于对照组（P＜0.05）。结论：高氧暴露所致BPD中，HMGB1表达增加。BPD的病理过程可能与HMGB1表达增加有关。［中国当代儿科杂志，2010，12（3）：219-223］

Abstract:

OBJECTIVE: To study the effect of hyperoxia exposure on high mobility group protein-B1 (HMGB1) expression in neonatal mice and the role of HMGB1 in the pathogenesis of bronchopulmonary dysplasia (BPD). METHODS: C57BL/6 mice were randomly exposed to 60% O2 or air 1 day after birth. BPD was induced by 60% O2 exposure. The pulmonary tissue samples were harvested 3, 7 and 14 days after exposure. The pathologic changes of pulmonary tissues were observed by hematoxylin and eosin staining, Masson staining and radical alveolar count. The expression of HMGB1 protein in lungs was detected by immunofluorescence. The expression of HMGB1 mRNA was detected by real-time fluorescent quantitative PCR. RESULTS: In the BPD group, the lungs developed decreased alceolar septation, swollen alveolar epithelium, stroma edema, interstitial fibrosis and developmental lag when compared with the control group. These changes became more obvious with more prolonged hyperoxia exposure. The expression of HMGB1 protein and mRNA 7 and 14 days after exposure increased significantly in the BPD group compared with that in the control group. CONCLUSIONS: Hyperoxia exposure results in an increase in lung HMGB1 expression. The increased HMGB1 expression may be associated with the development of BPD.［Chin J Contemp Pediatr, 2010, 12 (3):219-223］