角化细胞生长因子对内毒素诱导急性肺损伤的保护作用

目的 初步研究角化细胞生长因子(KGF)对脂多糖(LPS)诱导大鼠急性肺损伤(ALI)的保护作用及可能的机制.方法 将36只SD大鼠按随机数字表法分为3组,每组12只.模型组尾静脉注射LPS 5 mg/kg建立ALI动物模型.对照组和KGF组注射等量生理盐水.KGF组在注射LPS后气道给予KGF 5 mg/kg.8 h后处死各组大鼠观察肺组织病理改变,并测量肺血管通透性、肺上皮细胞通透性、肺湿/干重(W/D)比值以及Ⅱ型肺泡上皮细胞(ATⅡ)增殖、修复功能改变.结果 光镜下观察显示KGF可有效减轻LPS所致ALI的肺组织病理改变,表现为肺血管充血、水肿减轻,几乎无炎性细胞浸润.与模型组比较,KGF组肺血管通透性[(0.026±0.049)%比(0.087±0.027)%]和肺泡上皮通透性[(0.692±0.017)%比(0.931±0.029)%]及W/D比值(4.778±0.243比6.869±0.153)均明显降低(P<0.05或P<0.01),ATⅡ细胞增殖及修复功能则明显提高[ATⅡ数量(个):6.083±1.781比4.666±1.923,损伤面积(mm2):2.946±0.453比6.181±0.975,P<0.05和P<0.01].结论 KGF可减轻LPS所致ALI,其机制可能是通过增强ATⅡ细胞的增殖及修复能力从而起到有效的保护作用.

The protective effect of keratinocyte growth factor on lipopolysaccharide-induced acute lung injury in rat

Objective To investigate the protective effect of keratinocyte growth factor (KGF) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its potential mechanism in rats. Methods Thirty-six Sprague-Dawley (SD) rats were randomly divided into three groups, each group with 12 rats. LPS (5 mg/kg) was injected intravenously to induce ALI in model group, and same amount of normal saline was injected in control group and KGF group. The rats in KGF group were treated with KGF (5 mg/kg) intratracheally after injection of LPS. The rats were sacrificed after 8 hours, histologic assessments, wet/dry weight (W/D) ratio, pulmonary vascular permeability, lung epithelial cell permeability, the proliferation and repair capacity of type Ⅱ alveolar epithelial cells (ATⅡ) were analyzed. Results Under optical microscope, it was found that KGF could reduce injury to lung tissue induced by LPS. Compared with the model group, KGF could decrease pulmonary vascular permeability [(0.026±0.049)% vs. (0.087±0.027)%], lung epithelial cell permeability [(0.692±0.017)% vs. (0.931±0.029)%] and W/D ratio (4.778±0.243 vs. 6.869±0.153, P<0.05 or P<0.01), enhance the proliferation and repair capacity of ATⅡ cells (ATⅡ cells: 6.083±1.781 vs. 4.666±1.923, injury area (mm2): 2.946±0.453 vs. 6.181±0.975, P<0.05 and P<0.01). Conclusion KGF could reduce the injury to the lung in LPS-induced ALI, and it plays a protective role through enhancing the proliferation and repair capacity of ATⅡ cells.