目的 探讨汉防己甲素对脂多糖诱导的小鼠急性肺损伤的作用及机制。方法 将ICR小鼠根据体质量随机分为对照组、模型组、地塞米松组、汉防己甲素（19.5、39.0、78.0 mg/kg）组。给药干预3 d后除对照组小鼠鼻腔滴注无菌生理盐水外，其余各组均鼻腔滴注脂多糖生理盐水溶液构建急性肺损伤模型，24 h后进行对小鼠进行肺部影像学检查；并测定小鼠肺湿质量（W）与干质量（D）比值；利用苏木素–伊红（HE）染色观察肺组织病理形态学变化；采用酶联接免疫吸附测定（ELISA）检测支气管肺泡灌洗液（BALF）中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)含量；选用可见分光光度法检测肺组织中髓过氧化物酶（MPO）活性；Western blotting验证小鼠肺组织TNF-α受体1(TNFR1)与受体相互作用蛋白激酶1(RIPK1)蛋白表达水平；最后选择免疫荧光法检测小鼠肺组织TNFR1相对表达水平。结果 与模型组相比，汉防己甲素组小鼠肺部影像与组织病理改变减轻；汉防己甲素39.0、78.0 mg/kg组均可显著降低W/D值（P<0.01、0.001）；并显著降低IL-1β、IL-6、TNF-α含量（P<0.05、0.01、0.001）；且汉防己甲素78.0 mg/kg组可显著下调MPO的活性（P<0.05）;Western blotting结果显示，汉防己甲素39.0 mg/kg组可显著下调RIPK1蛋白相对表达量，汉防己甲素78.0 mg/kg组可显著下调TNFR、TNF-α的蛋白相对表达量（P<0.05）；免疫荧光结果也进一步验证汉防己甲素组可下调TNFR的荧光表达。结论 汉防己甲素能够减轻脂多糖诱导的小鼠急性肺损伤，其作用机制可能与TNF信号通路有关。

Objective To discuss the effect and mechanism of tetrandrine in mice model of acute lung injury induced by lipopolysaccharide. Methods ICR mice were randomly divided into control group, model group, dexamethasone group, tetrandrine（19.5, 39.0, and 78.0 mg/kg） group. After 3 days of drug intervention, except for the control group of mice, which received intranasal infusion of sterile physiological saline, all other groups received intranasal infusion of lipopolysaccharide physiological saline solution to construct acute lung injury model. After 24 hours, radiographic examination was performed on mice, and then mice were sacrificed to measure the ratio of wet weight（W） to dry weight（D） of the lungs, observe the pathological changes of lung tissue by HE staining.IL-1β, IL-6, and TNF-α levels in BALF were detected by ELISA. MPO activity in lung tissue was detected by visible spectrophotometry method, and Western blotting was used to verify the protein expression levels of TNFR1 and RIPK1 in mice lung tissue. Finally, immunofluorescence was used to detect the relative expression level of TNFR1 in mouse lung tissue. Results Compared with the model group, mice in the tetrandrine group had alleviated tissue pathology changes, and both tetrandrine 39.0 and 78.0 mg/kg groups could significantly reduce the W/D value（P＜0.01, 0.001）, significantly reduce IL-1β, IL-6, and TNF-α content（P＜0.05, 0.01, and 0.001）. And significantly reduce MPO activity in the tetrandrine 78.0 mg/kg group（P＜0.05）. Western blotting results showed that tetrandrine 39.0 mg/kg group could significantly downregulate RIPK1 protein expression, while the tetrandrine 78.0 mg/kg group could significantly downregulate TNFR and TNF-α protein expression（P＜0.05）. Immunofluorescence results also further verified that tetrandrine group can down-regulate the fluorescence expression of TNFR. Conclusion Tetrandrine can alleviate lipopolysaccharide induced acute lung injury in mice, and its mechanism of action may be related to the TNF signaling pathway.

R285.5

国家自然科学基金青年基金项目(82204740); 中国中医科学院优秀青年科技人才培养专项(ZZ16-YQ-027)