谷氨酰胺对新生大鼠高氧肺损伤的干预作用及其机制

doi:10.13481/j.1671-587x.20190401

摘要/Abstract

摘要： 目的：探讨谷氨酰胺（GLN）对高氧诱导下新生大鼠肺损伤的保护作用，并阐明其作用机制。方法：选取足月新生Wistar大鼠90只，雌雄不限，随机分为对照组（吸入氧浓度为21%）、高氧组（吸入氧浓度>85%）和高氧（吸入氧浓度>85%）+GLN组，每组30只，高氧组和高氧+GLN组大鼠制备高氧肺损伤（HALI）模型。从实验第1天开始，高氧+GLN组新生大鼠定时腹腔内注射GLN（0.75 g·kg^-1·d^-1），另外2组新生大鼠腹腔注射等量生理盐水。在实验开始的第3、7和14天测定各组大鼠体质量，检测各组大鼠肺组织含水量，采用HE染色法观察各组大鼠肺组织形态表现，应用酶联免疫吸附法（ELISA）检测各组大鼠肺组织匀浆中白细胞介素6（IL-6）、白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）水平。结果：实验第3、7和14天，与同时间对照组比较，高氧组大鼠体质量明显降低（P<0.05）；与同时间高氧组比较，高氧+GLN组大鼠体质量明显增加（P<0.05）。与同时间对照组比较，高氧组大鼠肺组织含水量明显增加（P<0.05），且高氧暴露时间越长升高越明显；与同时间高氧组比较，高氧+GLN组大鼠肺组织含水量明显降低（P<0.05）。与对照组比较，高氧组大鼠肺泡结构有一定程度的破坏，伴随肺泡融合、间隔增宽、间质炎性渗出及纤维组织增生等改变，高氧暴露时间越长损伤程度越重；与同时间高氧组比较，高氧+GLN组大鼠肺泡损伤程度、炎性渗出及纤维组织增生程度均减低。与同时间对照组比较，高氧组大鼠肺组织匀浆中IL-6、IL-1β和TNF-α水平明显升高（P<0.05）；与高氧组比较，高氧+GLN组大鼠肺组织匀浆中IL-6、IL-1β和TNF-α水平明显降低（P<0.05）。结论：GLN对新生大鼠HALI具有一定的保护作用，可缓解高氧诱导的肺组织水肿，减轻肺泡结构的损伤和破坏，并能抑制肺组织中IL-6、IL-1β和TNF-α表达。

关键词: 高氧肺损伤, 新生大鼠, 谷氨酰胺, 白细胞介素6, 白细胞介素1β, 肿瘤坏死因子α

Abstract: Objective:To explore the protective effect of glutamine(GLN) on the hyperoxia lung injury in the neonatal rats, and to elucidate its mechanism. Methods:A total of 90 male and female Wistar rats were selected and randomly divided into control group (FiO₂=21%), hyperoxia group(FiO₂> 85%) and hyperioxia + glutamine (GLN) group (FiO₂> 85%)(n=30).The rats in hyperioxia group and hyperioxia+GLN groups were used to establish the models of hyperoxia lung injury(HALI).The rats in hyperoxia+ GLN group were intraperitoneally injected with 0.75 g·kg^-1·d^-1 GLN from the first day of experiment, and the rats in other two groups were abdominally injected with the same volume of normal saline. The body weights, water contents in the lung tissue of the neonatal rats in various groups on the 3rd, 7th, and 14th days of the experiment were measured. HE staining was used to determine the morphology of lung tissue of the rats in various groups; ELISA was used to detect the levels of interleukin-6(IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the lung tissue homogenate of the rats in various groups. Results:Compared with control group at the same time, the weights of the neonatal rats in hyperoxia group were significantly decreased on the 3rd, 7th and 14th days(P<0.05); the body weights of neonatal rats in hyperoxia + GLN group were significantly higher than those in hyperoxia group at the same time (P<0.05). On the 3rd, 7th, and 14th days, the water contents of lung tissue of the rats in hyperoxia group were higher than those in control group at the same time(P<0.05), and the difference was gradually increased with the prolongation of time; the water contents of lung tissue of the rats in hyperoxia + GLN group were significantly lower than those in hyperoxia group(P<0.05) on the 3rd,7th, and 14th days. Compared with control group, there was a certain degree of damage of the alveolar structure of the rats in hyperoxia group,accompaying with the alveolar fusion, the interval widening, the fibrous tissue hyperplasia and the interstitial inflammatory exudation;the injury degree was aggravated with the prolongation of time. Compared with hyperoxia group, the degrees of alveolar injury, inflammatory exudation, fibrous tissue hyperplasia of the rats in hyperoxia + GLN group were alleviated. Compared with control group at the same time, the levels of IL-1β, IL-6 and TNF-α in lung tissue homogenate of the rats in hyperoxia group were significantly increased (P<0.05);compared with hyperoxia group, the levels of IL-1β, IL-6, and TNF-α of the rats in hyperoxia + GLN group were significantly decreased(P<0.05). Conclusion:GLN has a protective effect on the neonatal rats with HALI, which can alleviate the hyperoxia-induced pulmonary edema in the neonatal rats and inhibit the expressions of IL-6, IL-1β, and TNF-α in lung tissue.

Key words: hyperoxia lung injury, neonatal rats, glutamine, interleukin-6, interleukin-1β, tumor necrosis factor-α

中图分类号:

R725.6

王叶, 王红, 张书剑, 姬华祎, 金正勇. 谷氨酰胺对新生大鼠高氧肺损伤的干预作用及其机制[J]. 吉林大学学报(医学版), 2019, 45(04): 747-751.

WANG Ye, WANG Hong, ZHANG Shujian, JI Huayi, JIN Zhengyong. Intervention effect of glutamine on hyperoxia lung injury in neonatal rats and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2019, 45(04): 747-751.

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