高氧致新生鼠肾组织病理变化及肿瘤坏死因子α的表达

Changes in renal histology and expression of TNF-α of normobaric hyperoxia in neonatal rats

目的以高氧诱导建立慢性肺部疾病（CLD）的新生大鼠模型为对象.动态观察肺损伤过程中肾组织的病理变化.同时检测细胞因子包括肿瘤坏死因子α（TNF-α）在肾组织中的变化规律.以探讨高氧对肾脏的损伤及其发生机制。方法200只新生足月Wistar大鼠，体质量5.7g，分为2组，即高氧组100只，空气组100只。将高氧组采用高氧建立新生鼠CLD模型，在80％±5％氧气条件下持续暴露；空气组新生鼠生后在正常空气中暴露；于第1、3、7、14、21天各处死12只，光学显微镜下观察肾组织形态学改变.免疫组织化学动态检测肾组织中TNF-α电的表达部位和强度变化。结果病理组织学表明，与空气组比较，高氧组肾脏呈轻度改变，第3、7天主要为肾小管空泡变性、水肿、扩张，第14、21天可见肾间质血管扩张、充血，偶见肾小管出血、坏死，肾小管再生，未见肾纤维化。免疫组织化学检测结果显示，空气组大鼠肾组织内无或仅有少量TNF-α阳性细胞表达.高氧组各期显示出TNF-α阳性表达的细胞.广泛分布于肾小管上皮细胞。高氧组第3天肾组织TNF-d（0.49±0.02）表达增强（P〈0.05），第7天TNF-α（0.63±0.14）表达达高峰（P〈0.01）.第14天TNF-α（0.45±0.22）表达减弱，但仍具统计学意义（P〈0.05），而第21天TNF-α（0.32±0.05）表达减弱，与空气组TNF-α（0.29±0.04）比较，差异无统计学意义（P〉0.05）。结论吸人高氧的新生鼠可产生肾脏病理学轻度改变.细胞因子TNF-α在肾脏表达一过性增强.可能参与了肾脏损伤的发生。

Objective To dynamically observe the pathological changes in kidney tissue accompanying the lung injury in the neonatal rat model with chronic lung disease（CLD） induced by prolonged hyperoxia, detect the changes of tumor necrosis factor α （TNF-α in kidney tissue, and explore the kidney injury induced by hyperoxia and its mechanism. Methods A total of 200 full- term newborn Wistar rats（body weight of 5 - 7 g） were divided into 2 groups, hyperoxia group（n = 100） and room air group（n = 100）. The neonatal rats in the hyperoxia group were continuously exposed to 80 % ± 5 % oxygen, and the animals in the room air group were exposed in room air. Twelve rats in each group were sacrificed at the 1st, 3rd, 7th, 14th and 21st days, and the dynamic changes in renal histology and expression of TNF-α in kidney were monitored by immunohistochemical method. Results The histopathological examination showed that, compared with the room air group, mild changes in kidney was observed in the hyperoxia group, included renal tubular degeneration, edema, expansion at the 3rd and 7th days, visible renal interstitial vascular dilation and congestion at the 14th and 21st days, and occasionally, renal tubular hemorrhage, necrosis, renal tubular regeneration without renal fibrosis. The immunohistochemistry showed that there was no or only small amount of TNF-α-positive cells in the kidney tissue of the room air group, whereas TNF-α-positive cells were widely distributed in renal tubular epithelial cells of the hyperoxia group. The TNF-α expression in the hyperoxia group increased at the 3rd day（0.49 ± 0.02）（P 〈 0.05）, reached to the peak at the 7th day（0.63 ± 0.14）（/9 〈 0.01）, and decreased but remained statistically significant at the 14th day （0.45 ± 0.22, P 〈 0.05）, whereas the TNF-α expression at the 21st day decreased to the level（0.32 ± 0.05） which was not statistically significant compared with the room air group （0.29 ± 0.04）（P 〉 0.05）. Conclusion It is demonstrated that inhalation of hyperoxia could induce mild renal pathological changes in neonatal rats, and the increase in TNF-α expression in kidney may be involved in kidney damage.