白细胞介素-37及相关因子在急性肺损伤大鼠模型中的作用及意义

The role and significance of interleukin-37 and related factors in the model of acute lung injury of rats

目的 研究在急性肺损伤大鼠肺组织中白细胞介素-37(interleukin 37,IL-37)及相关因子的表达水平,阐述IL-37在急性肺损伤中的作用及意义,并进一步探究急性肺损伤发病机制。方法 将45只清洁级Wistar大鼠按随机数字表法分为健康对照组、博来霉素组、地塞米松治疗组,每组大鼠15只,博来霉素组及地塞米松治疗组大鼠气管内给予博来霉素4 mg/kg制作急性肺损伤模型,健康对照组给予相同体积生理盐水作为对照,地塞米松治疗组大鼠于急性肺损伤造模基础上第2 d每日腹腔注射地塞米松3 mg/kg,健康对照组、博来霉素组大鼠腹腔注射生理盐水作为对照。各组大鼠分别于造模后7、14、28 d处死,HE染色评价肺组织病理形态学变化,分别测定肺组织匀浆中IL-37、血清肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)含量,RT-PCR法检测肺组织IL-18mRNA表达量。结果 病理形态学检查提示:健康对照组大鼠在各时间点肺组织结构完整,无炎性及纤维化改变;博来霉素组、地塞米松治疗组大鼠肺组织由早期急性肺泡炎性改变发展为晚期纤维化性改变,地塞米松治疗组急性炎症及肺纤维化性改变在同时间点较博来霉素组减轻。博来霉素组、地塞米松治疗组的IL-37和TNF-α含量及IL-18 mRNA表达于第7 d升高至最高点,后逐渐降低,至第28 d均高于健康对照组,差异有统计学意义(P均<0.05)。结论 IL-37在大鼠急性肺损伤发病过程中起重要作用,该作用可能与调控IL-18、TNF-α转导有关。

Objective To study the expression of interleukin （IL）-37 and related factors in lung tissue of rats with acute lung injury, and explore the role and significance of IL-37 in acute lung injury so as to understand the pathogenesis of acute lung injury. Methods Forty-five clean-grade Wistar rats were randomly divided into a healthy control group, a bleomycin group and a dexamethasone treatment group, with 15 rats in each group. The rats in the bleomycin group and the dexamethasone group were treated with bleomycin at a dose of 4 mg/kg by intratracheal administration. The healthy control group was given the same volume of saline as control. The dexamethasone treatment group was injected with dexamethasone 3 mg/kg intraperitoneally twice a day on the basis of acute lung injury. The healthy control group and the bleomycin group were injected intraperitoneally with normal saline as control. The rats in each group were sacrificed at 7, 14 and 28 days after modeling. The histopathological changes of lung tissue were evaluated by HE staining. The levels of IL-37 in lung homogenate and tumor necrosis factor （TNF）-α in serum were measured. The expression of IL-18 mRNA in lung tissue was detected by RT-PCR. Results Pathological morphology showed that the lung tissue of the healthy control group was complete, no inflammatory and fibrotic changes at all time points. The lung tissues of the bleomycin group and the dexamethasone group manifested with acute alveolitis firstly and thus developed fibrosis changes lately, and the changes in the dexamethasone group were more slightly than those in the bleomycin group. The contents of IL-37 and TNF-α and the expression of IL-18 mRNA in the bleomycin group and the dexamethasone group reached to the highest point on the 7th day, and then decreased, but were significantly higher than those of the healthy control group on the 28th day （all P〈0.05）. Conclusions IL-37 plays an important role in the pathogenesis of acute lung injury in rats. This effect may be related to the regulation of IL-18 and TNF-α transduction.