维甲酸下调结缔组织生长因子表达减轻新生大鼠高氧肺损伤的研究

Retinoic acid protects neonatal rats from hyperoxia-induced lung injury through down-regulating connective tissue growth factor

摘要:

目的：探讨维甲酸（RA）对高氧肺损伤保护作用的机制。方法：90 只SpragueDawley新生鼠随机平分为空气组、高氧组和高氧+RA 组。高氧组、高氧+RA 组置于 85% 氧浓度的氧箱中，高氧+RA 组每日腹腔注射RA 500 μg/kg。分别于实验第 4天、7天、14天行开胸术取新生鼠肺组织，苏木精-伊红染色光镜下行辐射状肺泡计数，逆转录聚合酶链反应（RT-PCR）、免疫组化检测肺组织结缔组织生长因子（CTGF）表达。结果：与空气组相比，高氧组和高氧+RA 组肺组织随氧暴露时间延长，出现炎性细胞浸润，肺泡结构紊乱，肺泡数量减少，肺间隔增厚，其中高氧+RA 组病理改变明显轻于高氧组；在第7天和第14天，高氧组和高氧+RA组肺组织 CTGF 的 mRNA 和蛋白表达比空气组增加（P＜0.05）；且高氧+RA组中 CTGF 的 mRNA 和蛋白表达在第 14 d 比高氧组减少（P＜0.05）。结论：高氧暴露下新生鼠肺组织 CTGF 表达增加，RA 保护高氧肺损伤可能是通过下调 CTGF 表达。

Abstract:

OBJECTIVE: To explore the mechanism of retinoic acid (RA) protection against hyperoxia-induced lung injury. METHODS: Ninety Sprague-Dawley rats were randomly assigned into three groups (n=30 each): air control group (exposed to air) and hyperoxia groups (exposed to 85% oxygen) with and without RA treatment. The RA-treated hyperoxia group received an intraperitoneal injection of RA (500 μg/kg) daily. Lungs were removed by tnoracotomy 4, 7 and 14 days after exposure. Radical alveolar counts (RAC) were observed by hematoxylin and eosin staining under a light microscope. The mRNA level of CTGF in lungs was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of CTGF protein in lungs was detected by immunohistochemistry. RESULTS: With the prolonged hyperoxia exposure, the lungs developed inflammatory cell infiltration, alveolar structure disorders, a decrease in the number of alveoli, and alveolar interstitial thickening in the hyperoxia groups with and without RA treatment. Pathological changes in the RA-treated hyperoxia group were less severe than the untreated hyperoxia group. The CTGF mRNA and protein expression were up-regulated in the hyperoxia groups with and without RA treatment 7 and 14 days after exposure compared with the air control group. Significantly decreased CTGF mRNA and protein expression were noted in the RA-treated hyperoxia group compared with the untreated hyperoxia group 14 days after exposure. CONCLUSIONS: The expression of CTGF mRNA and protein increases in neonatal rats with hyperoxia-induced lung injury. RA may provide protections against the lung injury possibly through down-regulating CTGF expression.