高氧肺损伤大鼠晚期糖基化终末产物受体的表达及意义

RAGE Signaling in Lung of Newborn Rats of Hyperoxia-Exposed

目的探讨高氧致新生大鼠肺组织损伤过程中晚期糖基化终末产物受体(RAGE)的表达情况。方法将16只3日龄新生大鼠依据是否高浓度氧暴露随机分为空气组(空气环境下暴露7天)大鼠和高氧组(95%氧暴露7天)大鼠,并进行比较观察。在此实验结束后,留取大鼠的肺组织标本和静脉血标本,通过光镜观察并盲法评分比较其肺组织辐射状肺泡计数(radic alalveolar counts,RAC)、RT-PCR法检测肺组织匀浆RAGEmRNA表达、免疫组化法检测肺组织RAGE的表达情况、ELASA法检测血清及肺泡灌洗液(BALF)TNF及sRAGE的水平。结果高氧组大鼠组肺组织损伤RAC降低(t=14.87,P=0.000)、肺组织RAGEmRNA增加(t=9.7109,P=0.000)、RAGE蛋白表达增加、BALFTNF-α(t=9.807,P=0.000)增高、sRAGE水平下降(t=3.7484,P=0.000)。结论 RAG通路在新生大鼠高氧引致肺组织损伤中具有重要的作用。

Objective High concentration of inspired oxygen can be life saving in individuals with respiratory failure.However,exposure to very high concentration of oxygen for extended periods may also result in lung injury and death.Receptors for advanced glycation end-products（RAGE） are multi-ligand cell surface receptors predominantly localized to alveolar type I cells that influence development and hyperoxia-induced inflammationwe hypothesis that RAGE signaling functions during hyperoxia-induced lung damage.Methods Sixteen 3-day-old SD rats from two litters were randomly divided into two groups,as hyperoxia exposured group（A）,and air-exposed group（B）.The rats from the group A were placed in a sealed Plexiglas chamber with a minimal in-and outflow,providing six to seven exchanges per hour of the chamber volume and maintaining O2 levels above 95%.while the rats in the group B only exposed with air simultaneously.Seven days later,all of the rats were sacrificed,immunohistochemistry was used to value the expression of RAGE in lung tissue;The levels of TNFα and sRAGE in bronchoalveolar lavage fluid（BALF） were detected by ELASA;RAGE mRNA were detected by RT-PCR in tissue homogenates;also the value of RAC（radical alveolar counts） with histology.Results The expression of RAGE protein in group A was more than that of in group B.When compared to group B,the levels of TNFα in BALF and mRNA in lung tissue homogenates were more increased（t=9.807,P=0.000）（t=9.7109,P=0.000）,but sRAGE in BALF and RAC decreased in group A（t=14.87,P=0.000）（t=3.7484,P=0.000）.Conclusion RAGE signaling plays a role in hyperoxia-induced lung damage.