摘要
目的 探讨人白介素 10 （ hIL-10 ）预先给药对呼吸机相关性肺损伤 （ VILI ）大鼠炎性因子的影响。方法 健康雄性 SD 大鼠 36 只,体质量 220~300g ,随机分为 3 组 （ n =12 ）：对照组（ C 组）、大潮气量机械通气组 （ H 组）和 hIL-10 干预组 （ HI 组）。其中 C 组经口插管后维持自主呼吸4h ; H 组采用大潮气量机械通气建立大鼠 VILI 模型,阿曲库铵静脉输注抑制自主呼吸、维持肌松,接小动物呼吸机机械通气,呼吸参数设定：呼吸频率 40 次/ min ,通气时间 4h ,吸呼比为 1∶3 ,呼气末正压通气 0cmH 2 O ,吸入氧浓度为 21% ,潮气量 30ml /kg,根据体质量调节潮气量; HI 组在大潮气量机械通气开始前30min 从尾静脉注射 hIL-10 （剂量为 8000U /kg ）,余同H 组, C 组、 H 组给予等量的生理盐水。各组于通气 4h 后放血处死大鼠,收集大鼠血清和 BALF ,采用酶联免疫吸附测定法检测肿瘤坏死因子 α （ TNF-α ）、 IL-8 和细胞间黏附分子 1 （ ICAM-1 ）的浓度;取右上肺组织做病理切片, HE 染色镜下观察形态学变化。结果 光镜下观察显示 C 组肺泡结构无明显损伤; H组肺泡结构破坏严重,肺泡内渗出物、出血和间质水肿明显,可见明显肺泡腔融合,肺间隔增宽,大量炎性细胞浸润; HI 组肺组织结构有一定程度损伤,肺间隔有少量增厚,但较H 组减轻。与 C 组相比, H 组、HI 组血清和 BALF 中 TNF-α 、 IL-8 和 ICAM-1 水平均升高 （ P 〈0.05 或 P 〈0.01 ）;与 H 组相比,HI 组血清和 BALF 中 TNF-α 、 IL-8 和 ICAM-1 水平明显降低 （ P 值均 〈0.01 ）。结论hIL-10 作为机体重要的抗炎因子,可通过调节肺组织炎症反应,降低炎性细胞因子水平,在一定程度上减轻大鼠VILI 。
Objective To investigate the effect of human interleukin-10 （hIL-10） pretreatment effect on inflammatory factors in rats with ventilator-induced lung injury （VILI）. Methods 36 healthy male SD rats, weighing 220 to 300 g, were randomly divided into three groups （ n = 12） ：control group （C group）, high tidal volume mechanical ventilation group （H group） and hIL 10 treatment group （HI group）. C group maintained spontaneous breathing for four hours after orotraeheal intubation. In H group, VILI model was made by high tidal volume mechanical ventilation, atracurium infusion was used to inhibit spontaneous breathing and maintain muscle relaxation, small animal ventilator was used for mechanical ventilation, respiratory parameters ： respiratory frequency was 40/rain, duration of ventilation was four hours, inspiration time/expiratory time was 1 ： 3, positive end expiratory pressure was 0 cm H2O, inhaled oxygen concentration was 21%, tidal volume was 30 ml/kg, regulating according to the body weight. HI group was injected with hIL-10 （8 000 U/kg） through tail vein at 30 rain before high tidal volume mechanical ventilation, C group and H group were given the same amount of saline. In each group, the rats were sacrificed after ventilation for four hours. The serum and bronchoalveolar lavage fluid （BALF） were collected to detect the concentrations of tumor necrosis factor-α （TNF-α）, interleukin-8 （IL-8） and intercellular adhesion molecule-1 （ICAM-1） by enzyme-linked immunosorbent assay. The right lung tissue pathological slices were taken to observe the morphological changes by HE staining. Results The pathological changes were observed under light microscope. There was no obvious alveolar structure damage in C group. In H group, there were alveolar structure destruction, alveolar exudation, hemorrhage and interstitial edema, visible alveolar fusion, pulmonary sental thickening, inflammatory cell infiltration. In HI group, there was a certain degree of damage in lung tissue structure, a small amount of pulmonary septal thickening, but lighter than that in H group. Compared with C group, the concentrations of TNF-α, IL-8 and ICAM 1 in serum and BALF of H group and HI group were increased （ P 〈0.05 or P 〈0.01）. Compared with H group, inflammatory cytokine levels in the serum and BALF of HI group were significantly decreased （all P 〈0.01）. Conclusions As an important anti-inflammatory factor, hIL-10 can reduce VILI in rats in a certain extent by regulating the inflammatory response of the lung and reducing the levels of inflammatory cytokines.
出处
《国际呼吸杂志》
2016年第22期1718-1722,共5页
International Journal of Respiration
基金
福建省中青年教师教育科研项目（JK2014017）
关键词
白介素10
机械通气
急性肺损伤
呼吸机相关性肺损伤
Interleukin-lO
Mechanical ventilation
Acute lung injury
Ventilator-induced lung injury
