高体积分数氧暴露对早产新生大鼠肺组织微小RNA-125b、肿瘤坏死因子-α和白细胞介素6表达的影响  

Effect of hyperoxia exposure on expression of microRNA-125b and tumor necrosis factor alpha, interleukin-6 in lung tissues of premature newborn rats

作　　者：张潇月 蔡成[1] 楚晓云 周慧琳 Zhang Xiaoyue;Cai Cheng;Chu Xiaoyun;Zhou Huilin(Department of Neonatology, Children′s Hospital Affiliated to Shanghai Jiaotong University, Shanghai Children′s Hospital, Shanghai 200062, China)

机构地区：[1]上海交通大学附属儿童医院,上海市儿童医院新生儿科,200062

出　　处：《中华实用儿科临床杂志》2019年第16期1244-1248,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金面上项目(81571467).

摘　　要：目的探讨高体积分数氧(高氧)暴露对早产新生SD大鼠肺组织中微小RNA 125b(miR-125)和肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)表达水平的影响。方法将80只早产SD大鼠出生24 h按随机数字表法分为空气组和高氧组。将高氧组早产大鼠暴露于氧箱中,调节氧流量1~3 L/min,氧体积分数维持(800±50) mL/L;空气组置于同一室内常压空气中,氧体积分数为210 mL/L,饲养条件相同。分别于不同时间点(1、4、7、10、14 d)提取各组及各个时间点早产SD大鼠肺组织标本,采用苏木精-伊红(HE)染色法观察肺组织病理变化,应用反转录聚合酶链反应(RT-PCR)及酶联免疫吸附试验(ELISA)检测不同时间点高氧暴露肺损伤肺组织中miR-125b、TNF-α及IL-6的表达情况。结果与空气组相比,高氧组早产大鼠肺组织miR-125b的表达自第1天后缓慢增加,第10天达到最高值(2.554±0.323),第14天表达量略有下降(2.329±0.263),各时间点组间比较差异均有统计学意义(均P<0.05);TNF-α自第7天开始增高[(78.55±39.53) ng/L],且在第10天显著增高[(80.16±11.24) ng/L],差异有统计学意义(P<0.05);IL-6自第7天起开始增高[(45.44±31.94) ng/L],在第10天显著增高[(90.38±8.24) ng/L],差异均有统计学意义(均P<0.05)。高氧组中,miR-125b与TNF-α不存在显著线性相关(r=0.132,P>0.05),miR-125b与IL-6呈正相关(r=0.439,P<0.05)。结论miR-125b与TNF-α、IL-6均参与高氧暴露所致支气管肺发育不良的发病过程,IL-6可能为其关键因子。Objective To observe the expression of microRNA-125b (miR-125), tumor necrosis factor alpha (TNF-α) and interleukin-6(IL-6) in premature rats exposed to hyperoxia. Methods Eighty 1-day old Sprague Dawley (SD) rats were randomly divided into an air group and a hyperoxia group.The rats in the hyperoxia group were continuously exposed to oxygen chamber for 1-3 L/min, oxygen volume fraction was maintained at (800±50) mL/L, and the rats in air group were placed in the same room with the oxygen volume fraction at 210 mL/L.The feeding conditions were same in 2 groups.Lung tissues of premature rats were extracted at different time (1, 4, 7, 10, 14 days). The pathologic changes in the lung tissues were observed by hematoxylin-eosin (HE) staining.The levels of miR-125b and TNF-α, IL-6 in lung tissues were detected by reverse transcription polymerase chain reaction (qRT-PCT) and enzyme-linked immunosorbent assay (ELISA). Results Compared with the air group, miR-125b in the hyperoxia group increased slowly after day 1, reached the highest in day 10 (2.554±0.323), and the relative expression in day 14 decreased slightly(2.329±0.263), and there were significant differences between 2 groups at di-fferent time (all P<0.05);in particular TNF-α level increased in day 7 [(78.55±39.53) ng/L], and reached the peak at day 10 [(80.16±11.24) ng/L], and there was a significant difference(P<0.05);IL-6 levels increased at day 7 [(45.44±31.94) ng/L], and reached the peak at day 10 [(90.38±8.24) ng/L], and there was a significant difference(P<0.05). There was a no significant correlation between miR-125b and TNF-α in the hyperoxia groups (r=0.132, P>0.05), but there was significant correlation between miR-125b and IL-6 in hyperoxia groups(r=0.439, P<0.05). Conclusions The levels of miR-125b, TNF-α and IL-6 are involved in the pathological process of bronchopulmonary dysplasia induced by hyperoxia, and IL-6 may be the key factor for miR-125b.

关 键 词：高体积分数氧暴露 大鼠 早产 肺损伤 微小RNA-125b 肿瘤坏死因子-A 白细胞介素6 

分 类 号：R722.6[医药卫生—儿科] R-332[医药卫生—临床医学]