目的 探究漆黃素通過(guò)激活沉默信息調(diào)節(jié)因子1（SIRT1）/核因子E2相關(guān)因子2（Nrf2）信號(hào)通路對(duì)急性呼吸窘迫綜合征大鼠鐵死亡的影響。方法 將SD大鼠隨機(jī)分為對(duì)照組、模型組以及漆黃素1、2、4 mg/kg組和漆黃素（4 mg/kg）＋SIRT1抑制劑（10 mg/kg EX-527）組，每組各14只。漆黃素、SIRT1抑制劑于造模前30 min ip給藥，對(duì)照組、模型組ip給予等量生理鹽水。除對(duì)照組外，其余各組大鼠均采用氣管內(nèi)滴注脂多糖法建立急性呼吸窘迫綜合征模型。檢測(cè)支氣管肺泡灌洗液（BALF）中炎性因子白細(xì)胞介素-6（IL-6）、腫瘤壞死因子-α（TNF-α）水平；測(cè)定肺組織濕/干質(zhì)量比（W/D）；HE染色觀察肺組織病理改變；檢測(cè)肺組織中鐵死亡相關(guān)指標(biāo)活性氧（ROS）、鐵、谷胱甘肽（GSH）、丙二醛（MDA）水平；免疫印跡法檢測(cè)肺組織中SIRT1/Nrf2信號(hào)通路相關(guān)蛋白表達(dá)。結(jié)果 與模型組比較，漆黃素各劑量組BALF中IL-6、TNF-α水平降低，肺組織W/D比值降低，肺組織中ROS、鐵、MDA水平降低，GSH水平升高，肺組織中SIRT1、核Nrf2蛋白水平升高（P<0.05），且4 mg/kg漆黃素干預(yù)的改善效果更顯著；在4 mg/kg漆黃素干預(yù)的基礎(chǔ)上增加SIRT1抑制劑后，漆黃素的改善作用被削弱。結(jié)論 漆黃素對(duì)脂多糖誘導(dǎo)的急性呼吸窘迫綜合征有保護(hù)作用，能夠改善鐵死亡，可能是通過(guò)激活SIRT1/Nrf2信號(hào)通路實(shí)現(xiàn)的。

Objective To investigate the influence of fisetin on ferroptosis in rats with acute respiratory distress syndrome (ARDS) by activating the silent information regulation 1 (SIRT1)/nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Methods SD rats were randomly divided into control group, model group, fisetin (1, 2, and 4 mg/kg) groups, and 4 mg/kg fisetin + SIRT1 inhibitor (10 mg/kg EX-527) group, each group had 14 rats. Fisetin and SIRT1 inhibitor were ip administered with 30 min before modeling, and the control group and model group were ip administered with the same amount of normal saline. Except the control group, the rats in other groups were used to establish the ARDS model by intratracheal instillation of lipopolysaccharide (LPS). Levels of inflammatory factor IL-6 and TNF-α in BALF were detected. The wet/dry mass ratio (W/D) of lung tissue was measured. Pathological changes in lung tissue treated by HE staining were observed. The levels of reactive oxygen species (ROS), iron, GSH, and MDA in lung tissue were measured. The expression of SIRT1/Nrf2 signaling pathway related proteins in lung tissue were detected by Western blotting method. Results Compared with the model group, the levels of IL-6 and TNF-α in the BALF of fisetin groups were decreased, the W/D ratio in lung tissue were decreases, the levels of ROS, iron, and MDA in lung tissue were decreased, while GSH levels were increased, and the levels of SIRT1 and nuclear Nrf2 proteins in lung tissue were increased (P < 0.05). Moreover, the improvement effect of 4 mg/kg fisetin intervention was more obvious. After the addition of SIRT1 inhibitor on the basis of 4 mg/kg fisetin intervention, the improvement effect of 4 mg/kg fisetin was weakened. Conclusion Fisetin has protection on LPS induced ARDS and can improve ferroptosis, which may be achieved by activating SIRT1/Nrf2 signaling pathway.

R285

四川省衛(wèi)生健康科研課題普及項(xiàng)目（19PJ1182）