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目的：探讨甜橙黄酮通过AMP依赖的蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路对呼吸道合胞病毒（RSV）感染大鼠肺组织损伤的改善作用。方法：将30只雄性Wistar大鼠分为对照组、模型组、甜橙黄酮低剂量组（14 mg/kg）、甜橙黄酮中剂量组（28 mg/kg）、甜橙黄酮高剂量组（56 mg/kg）、甜橙黄酮高剂量+AICAR组（56 mg/kg+500 mg/kg的AMPK激活剂AICAR），计算大鼠肺指数。实时荧光定量聚合酶链式反应（qRT-PCR）法测定肺组织RSV病毒载量，酶联免疫吸附（ELISA）法测定大鼠肺泡灌洗液炎症因子水平，HE染色测定肺组织病理，蛋白免疫印迹（Western blot）法测定AMPK/mTOR通路蛋白表达。结果：与对照组相比，模型组大鼠肺组织存在炎性浸润，排列松散，肺指数、肺组织RSV病毒载量、肺泡灌洗液白细胞介素（IL）-1β、IL-6、肿瘤坏死因子-α（TNF-α）水平、炎症评分、p-AMPK/AMPK、mTORC1蛋白表达升高（P＜0.05）；与模型组相比，甜橙黄酮低剂量组、甜橙黄酮中剂量组、甜橙黄酮高剂量组大鼠肺组织损伤减轻，大鼠肺指数、肺组织RSV病毒载量、肺泡灌洗液IL-1β、IL-6、TNF-α水平、炎症评分、p-AMPK/AMPK、mTORC1蛋白表达降低（P＜0.05）；与甜橙黄酮高剂量组相比，甜橙黄酮高剂量+AICAR组大鼠肺组织损伤加重，肺指数、肺组织RSV病毒载量、肺泡灌洗液IL-1β、IL-6、TNF-α水平、炎症评分、p-AMPK/AMPK、MTORC1蛋白表达升高（P＜0.05）。结论：甜橙黄酮可能通过抑制AMPK/mTOR信号通路发挥对RSV诱导的大鼠抗炎、抗病毒、抗肺部损伤作用。

英文摘要:

Objective: To investigate the ameliorating effect of Sinensetin on lung tissue damage in rats infected with respiratory syncytial virus (RSV) through AMP-dependent protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. Methods: 30 male Wistar rats were grouped into control group, model group, low-dose Sinensetin group (14 mg/kg), medium-dose Sinensetin group (28 mg/kg), high-dose Sinensetin group (56 mg/kg), high-dose Sinensetin combined AICAR group (56 mg/kg combined 500 mg/kg of AMPK activator AICAR), the lung index of rats was calculated. The viral load of RSV in lung tissue was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The levels of inflammatory factors in alveolar lavage fluid of rats were determined by enzyme-linked immunosorbent assay (ELISA). Lung histopathology was determined by HE staining, and Western blot was used to measure the expression of AMPK/mTOR pathway proteins. Results: Compared with the control group, the lung tissue of the model group had inflammatory infiltration, and was loosely arranged, the lung index, RSV viral load in lung tissue, levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid, inflammation score, expression of p-AMPK/AMPK and mTORC1 protein increased (P<0.05). Compared with the model group, the rats of the low-dose Sinensetin group, the medium-dose Sinensetin group, and the high-dose Sinensetin group had reduced lung tissue damage, the lung index of rats, RSV viral load in lung tissue, levels of IL-1β, IL-6, TNF-α in bronchoalveolar lavage fluid, inflammation score, expression of p-AMPK/AMPK, and mTORC1 decreased (P<0.05). Compared with the high-dose Sinensetin group, the lung tissue damage of the rats of the high-dose Sinensetin combined AICAR group was aggravated, the lung index, RSV viral load in lung tissue, levels of IL-1β, IL-6, TNF-α in bronchoalveolar lavage fluid, inflammation score, expression of p-AMPK/AMPK and MTORC1 increased (P<0.05).Conclusion: Sinensetin may play anti-inflammatory, anti-viral and anti-lung injury effects on RSV-induced rats by inhibiting the activation of AMPK/mTOR signaling pathway.

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