胰岛素样生长因子-1在油酸致急性肺损伤小鼠中的作用

Variation of insulin-like growth factor-1 with time in acute lung injury induced by oleic acid in a rat model

目的胰岛素样生长因子-1(IGF-1)在油酸致急性肺损伤小鼠模型中的变化规律,及在急性肺损伤中的作用。方法通过小鼠尾静脉注射油酸(0.3 ml/kg)建立急性肺损伤小鼠模型,8 h断颈法处死小鼠,进行肺湿/干重(W/D)比值的测定和苏木精-伊红(HE)染色,判断造模的效果。健康BALB/c小鼠60只,随机分为油酸组(35只)和对照组(25只)。油酸组从尾静脉注入0.3 ml/kg的油酸,对照组从尾静脉注入同等体积的生理盐水。两组分别于1、3、7、14、21、28 d观察小鼠的中毒表现,并各处死3只小鼠取左肺进行HE和Masson染色观察肺组织的病理改变,同时眼眶采血测定血清IGF-1含量。结果油酸注入后10 mins^1 h小鼠开始出现呼吸困难,8 h时检测肺湿/干重比明显增加,肺组织病理表现为肺泡及肺间质大量中性粒细胞浸润,肺泡隔增厚,肺间质水肿,肺泡腔内充满水肿液,肺内小血管及肺泡隔毛细血管扩张充血明显,部分肺泡出血。各时段油酸组IGF-1水平增加,第7天出现急剧地升高,然后趋向平缓,较对照组差异有统计学意义(P=0.000)。油酸组小鼠第1~3天病理特征为明显肺泡炎改变;第7~21天肺泡炎症改变减轻,纤维增生明显,支气管周围、肺泡间隔及肺泡腔内出现纤维化;第28天纤维增生趋向于平缓。结论油酸致急性肺损伤小鼠细胞因子IGF-1水平随时间递增,其变化趋势与组织病理的纤维化进程一致,提示IGF-1在ARDS的发病过程中可能起到了重要的作用,并可促进其纤维增生的进程。

Objective To observe the variation of insulin-like growth factor-1 （IGF-1） with time and investigate its role in acute lung injury（ALl） induced by oleic acid in a rat model. Methods The mice were injected with oleic acid （0.3 ml/kg） intravenously to induce ALI. The wet/dry weight （W/D） of the right lung were examined and sections of left lung were stained with hematoxylin eosin to estimate the effect in rat model of ALI at 8 hours later after oleic acid treatment. Sixty BALB/c mice were randomly divided into an oleie acid group （n = 35） and a control group （n = 25）. The oleic acid group was treated with oleic acid （0.3 ml/kg） intravenously and the control group was treated with same amount of normal saline. 3 rats in each group respectively were sacrificed on 1 st, 3 rd, 7 th, 14 th, 21 th and 28 th day after the treatment. Pathological changes were observed in sections of left lung stained with hematoxylin eosin and Masson, meanwhile, the levels of IGF-1 in serum were measured. Results The mice began to have difficulty breathing after 10 rains-1 h with oleic acid （0.3 ml/kg） intravenously. After 8h with oleic acid treatment, the W/D was much higher inthe oleic acid group than that in the control group. Moreover, the characteristics of the lung pathologic histology were the infiltration of a large number of neutrophils in the alveoli and interstitial tissue, thickening of alveolar septa, alveolar and interstitial pulmonary edema, congestion, diffuse dilation of pulmonary capillaries and alveolar hemorrhage. The expression of IGF-1 significantly increased in the oleic acid group compared with the control group on different time points （P= 0.000）. The curve showed there was an obvious increasing tendency on 7th day. The phase in early （1-3 d） was characterized by acute alveolitis. The phase in later stage （7-21 d） was characterized by marked proliferation of fibrous tissue. It would become slower after 28 th day. Conclusions The expression of IGF-1 is increased with the time which is consistent with the progression of pulmonary fibrosis in the comparison of the lung histopathological examination in acute lung injury induced by oleic acid in a rat model.