目的：研究自噬抑制剂3-甲基嘌呤（3-MA）对脂多糖（LPS）诱导小鼠急性肺损伤的保护作用及其机制。方法：取小鼠随

机分为正常对照组、模型（LPS 15 mg/kg）组、药物对照（3-MA 20 mg/kg）组和低、高剂量治疗（LPS 15 mg/kg+3-MA 20、40 mg/kg）

组，每组10 只。除正常对照组和药物对照组外，其余各组小鼠ip LPS复制急性肺损伤模型，药物对照组和低、高剂量治疗组小鼠

分别于建模前1 h ip 相应剂量的3-MA。建模6 h 后分别测量各组小鼠的肺湿/干质量比（W/D），HE染色观察肺组织病理变化；

Western blot 法检测肺组织肿瘤坏死因子α（TNF-α）、NF-κB p65、LC3BⅡ/Ⅰ、激活型半胱氨酸氨基蛋白酶3（Cleaved-caspase-3 蛋白

的表达水平。结果：与正常对照组比较，模型组小鼠的W/D值和TNF-α、NF-κB p65、LC3BⅡ/Ⅰ、Cleaved-caspase-3 蛋白表达均增

强（P＜0.01）；与模型组比较，低剂量治疗组小鼠的W/D值和TNF-α、NF-κB p65、LC3BⅡ/Ⅰ、Cleaved-caspase-3 蛋白表达均减弱

（P＜0.05），高剂量治疗组小鼠仅LC3BⅡ/Ⅰ蛋白表达减弱（P＜0.01）。结论：在LPS诱导的急性肺损伤小鼠模型中，过度自噬可能

通过激活NF-κB 通路参与炎症反应并诱导细胞凋亡；3-MA适度抑制自噬可减轻炎症反应并起到保护肺组织的作用。

OBJECTIVE：To study the protective effects of autophagy inhibitor 3-Methyladenine（3-MA）against lipopolysaccharide（

LPS）-induced acute lung injury in mice and its mechanism. METHODS：Mice were randomly divided into normal control

group，model group（LPS 15 mg/kg），drug control group（3-MA 20 mg/kg），low-dose and high-dose groups（LPS 15 mg/kg+

3-MA 20，40 mg/kg），with 10 mice in each group. Except for normal control group and drug control group，other groups were given

LPS intraperitoneally to induce acute lung injury model，and drug control group and low-dose and high-dose groups were given

equivalent dose of 3-MA intraperitoneally 1 h before modeling. 6 h after modeling，lung wet/drug mass ratio（W/D）was determined

respectively，and pathology change of lung tissue was observed by HE staining. TNF-α ，NF-κ B p65，LC3B Ⅱ/Ⅰ and

Cleaved-caspase-3 protein expression were detected by Western blot. RESULTS：Compared with normal control group，W/D，

TNF-α，NF-κB p65，LC3BⅡ/Ⅰ and Cleaved-caspase-3 protein expression increased in model group（P＜0.01）. Compared with

model group，W/D，the expression of TNF-α，NF-κB p65，LC3BⅡ/Ⅰ and Cleaved-caspase-3 protein decreased in low-dose group

（P＜0.05），white just only LC3BⅡ/Ⅰ protein decreased high-dose group（P＜0.01）. CONCLUSIONS：In LPS-induced acute lung

injury model in mice，the excessive autophagy could activate the NF-κB pathway and involve the inflammatory responses and induce

lung cells apoptosis. The moderate autophagy inhibition by 3-MA can ameliorate inflammatory response and protect lung tissue.