角质细胞生长因子-2对脂多糖所致大鼠急性肺损伤的保护作用  

Protective Effects of Keratinocyte Growth Factor-2 on Lipopolysaccharide-Induced Acute Lung Injury in Rats

作　　者：童琳[1] 朱晓丹[1] 刘洁[1] 毕晶[1] 戎琳怡[1] 宋元林[1] 白春学[1] 

机构地区：[1]复旦大学附属中山医院呼吸内科,上海200032

出　　处：《中国临床医学》2013年第6期747-750,共4页Chinese Journal of Clinical Medicine

基　　金：国家自然科学基金重点项目(编号:30930090);国家自然科学基金青年科学基金项目(编号:81100046)

摘　　要：目的:观察静脉注射不同剂量角质细胞生长因子-2(keratinocyte growth factor-2,KGF-2)对脂多糖(lipopolysaccharide,LPS)所致大鼠急性肺损伤的保护作用。方法:采用气道内滴注LPS(5 mg/kg)的方法建立大鼠急性肺损伤模型,以相同体积磷酸盐缓冲液(PBS)气道内滴注作为对照。LPS滴注完毕1 h后,经尾静脉注射KGF-2(5、10及20 mg/kg);LPS气道内滴注24 h后,进行动脉血气分析,检测肺组织湿/干质量比、肺泡灌洗液总蛋白浓度、肺泡灌洗液炎性因子水平,并行肺泡灌洗液白细胞计数、白细胞分类计数以及肺组织病理检查。结果:LPS致伤组动脉血氧分压较对照组显著降低,而其肺泡灌洗液总蛋白浓度、肺泡灌洗液白细胞数及中性粒细胞数、肺组织湿/干质量比均较对照组显著升高,差异均有统计学意义(P<0.05)。肺组织病理检查结果提示,LPS致伤组炎性细胞浸润、肺组织实变、间质水肿等损伤表现显著。不同剂量KGF-2静脉注射对LPS所致急性肺损伤均有不同程度的保护作用,但剂量为10 mg/kg时保护作用最明显。LPS致伤组肺泡灌洗液中巨噬细胞炎性蛋白2(macrophage inflammatory protein 2,MIP-2)、白细胞介素-6(interleukin 6,IL-6)水平均较对照组显著升高(P<0.05),而KGF-2给药组MIP-2、IL-6水平均较LPS致伤组明显降低,差异均有统计学意义(P<0.05)。结论:KGF-2对LPS所致急性肺损伤有明显的保护作用,KGF-2在急性肺损伤的治疗中可能有应用前景。Objective：To investigate the therapeutic effects of keratinocyte growth factor-2（KGF-2） on acute lung injury induced by lipopolysaccharide（LPS） in rats.Methods：LPS（5 mg/kg） was administered intratracheally to induce rat acute lung injury model.KGF-2 （5,10 and 20 mg/kg） was intravenously injected 1 h after LPS challenge.Arterial blood gases,lung tissue wet-to-dry weight ratio,total protein,number of leukocytes and neutrophils in bronchoalveolar lavage fluid,histological changes,and inflammatory factor levels were analyzed 24 h after LPS was intratracheally administered.Results：Compared with control,LPS instillation resulted in significantly decreased PaO2 and elevated lung wet-to-dry weight ratio,total protein,number of leukocytes and neutrophils in bronchoalveolar lavage fluid.The differences were statistically significant（P＜0.05）.The pathological results showed that there were inflammatory cell infiltration,lung tissue consolidation and interstitial edema in LPS induced group.Treatment with KGF-2 significantly improved the above lung injury parameters,and treatment with a dose of 10 mg/kg showed maximum improvement in lung injury.LPS induced significant elevation of macrophage inflammatory protein 2 （MIP-2） and interleukin-6（IL-6） in bronchoalveolar lavage fluid,whereas treatment with KGF-2 markedly reduced the levels of MIP-2 and IL-6（P＜0.05）.The differences were statistically significant（P＜0.05）.Conclusions：Intravenous administration of KGF-2 attenuates lung injury induced by LPS,suggesting that KGF-2 may have potential in the treatment of acute lung injury.

关 键 词：角质细胞生长因子-2 脂多糖 急性肺损伤 

分 类 号：R563.8[医药卫生—呼吸系统]