摘要
目的探讨维甲酸(RA)对高氧肺损伤保护的作用机制及其与调控丝裂原活化蛋白激酶(MAPKs)的关系。方法剖宫取出SD大鼠孕21 d(足月为22 d)早产鼠,随机分为4组(每组n=12):①空气组;②高氧组;③空气+RA组;④高氧+RA组,①、③组置于空气中,②、④组置于85%O2中,③、④组每日腹腔注射RA(500μg/kg)。4 d后收集肺组织标本,末端标记法(TUNEL)检测细胞凋亡,免疫组化SP法检测PCNA表达,Western Blot检测磷酸化/非磷酸化总ERKsJ、NKs或p38表达。结果与空气组比较,高氧暴露使肺组织TUNEL阳性细胞显著增加(P<0.01),PC-NA表达明显受抑(P<0.01),肺泡分隔第二嵴明显减少、气腔增大,磷酸化ERK1/2J、NK1/2和p38表达不同程度增加;RA显著缓解高氧所致上述改变。结论RA通过调节MAPKs活性状况,降低肺细胞凋亡,促进其增殖,是防止高氧肺损伤的重要机制之一。
Objective To investigate the protective effect of retinoic acid (RA) on hyperoxia lung injury and the role of RA as a modulator on mitogen-activated protein kinases (MAPKs). Methods Gastation 21 day Sprague-Dawley (SD) fetuses (term = 22 day) were delivered by hysterotomy. Premature rat pups were randomly divided into 4 groups as Ⅰ . Air-exposed control group;Ⅱ . hyperoxia-exposed group; Ⅲ air-exposed plus RA group, Ⅳ. hyperoxia-exposed plus RA group. Group Ⅰ , Ⅲ were remained in room air, and groupⅡ , Ⅳ were placed in 85 % oxygen. The pups in m, Ⅳ were injected with RA (500 μg/kg, every day) intraperitoneally. All lung tissues of premature rat pups were collected 4 day after birth. Terminal Transferase d-UTP nick end labeling(TUNEL) staining detected cell apoptosis. The expression of PCNA was detected by Immunohistochemistry. Western Blot Analyses for Phosphorylated and Total Nonphosphorylated ERKs, JNKs or p38. Results Compared with air group, pups exposed to hyperoxia for 4 day exhibited TUNEL-positive nuclei increased remarkedly( P 〈 0.01 );There was an obvious depression in parenchymal PCNA staining( P 〈 0.01 ) ;The air-space size was significantly greater and secondary crests were markedly reduced, phosphorylated ERK1/2,JNK1/2 and p38 proteins increased to different degrees. RA improved those changes mentioned above significantly. Conclusion RA could decrease pneumocyte apoptosis and stimulate pneumocyte proliferation in hyperoxia condition. The protection of RA on hyperoxia lung injury was related to regulating activation of MAP kinases.
出处
《基础医学与临床》
CSCD
北大核心
2006年第2期143-148,共6页
Basic and Clinical Medicine
基金
国家自然科学基金(30471824)
"十五"国家科技攻关计划项目(2004BA702A11)
关键词
高氧肺损伤
丝裂原活化蛋白激酶
维甲酸
hyperoxia lung injury
mitogen-activated protein kinases
retinoic acid