Abstract：【Objective】 To investigate the effect of quercetin (QUE) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice and study its mechanism. 【Methods】 Sixty male C57bl/6 mice were randomly divided into 4 groups (15 in each group): normal group (CON group), LPS group and QUE treatment group. The ALI mice were constructed by intraperitoneal injection of LPS (10 mg/kg). The CON group was given the same amount of normal saline, while the QUE treatment group were given QUE 25 mg/kg 2 hours before the administration of LPS. The mice in both CON group and The LPS group were given the same amount of DMSO. HE staining was used to detect lung histopathological changes. Western blotting was used to detect the expression of PERK and key proteins in the apoptosis pathway. Lung tissue oxidative stress levels were detected with malondialdehyde(MDA). Counted Inflammatory cells in bronchoalveolar lavage fluid (BLAF) and myeloperoxidase (MPO) activity in lung tissue were used to detect with inflammatory response. 【Results】 Quercetin alone had no effect on the morphology and inflammation of lung tissue in mice. Intraperitoneal injection of LPS induced pathological damage of mouse lung tissue which increased the number of total cells and neutrophils in BALF, increased MPO activity, and increased the levels of TNF-α and IL-1β in lung tissue. However, the QUE prevention group and the QUE treatment group significantly alleviated the above changes. Western blotting results showed that QUE pretreatment inhibited the expression of proteins related to the endoplasmic reticulum stress PERK (double-stranded RNA-dependent protein kinase ER kinase) signaling pathway and reduced the expression of caspase-3, a key protein in the apoptosis pathway. 【Conclusion】 Quercetin can reduce ALI in mice induced by LPS by inhibiting endoplasmic reticulum stress (ERS) and reducing oxidative stress and inflammation. The mechanism is related to the inhibition of PERK signaling pathway of ERS.
[1] THOMPSON B T, CHAMBERS R C, LIU K D. Acute respiratory distress syndrome[J].N Engl J Med,2017,377(6):562-572.
[2] BELLANI G, LAFFEY J G, PHAM T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries[J].JAMA,2016,315(8):788-800.
[3] LI X, MA X. Acute respiratory failure in COVID-19: is it "typical" ARDS[J].Crit Care,2020,24(1):198-198.
[4] 韦祖猛, 黄卫清, 赵宁波, 等. 基于网络药理学及分子对接技术的痰热清胶囊治疗新冠肺炎的物质基础及机制研究[J].中国中医急症, 2020,29(10):1706-1710.
[5] 金星, 郑丰杰. 急性肺损伤中医学发病机制及治疗思路探讨[J].中医药临床杂志, 2008,(1):76-77.
[6] DARBAND S G, KAVIANI M, YOUSEFI B, et al. Quercetin: A functional dietary flavonoid with potential chemo-preventive properties in colorectal cancer[J].J Cell Physiol,2018,233(9):6544-6560.
[7] 肖晓辉, 付明生, 万毅新. 槲皮素对百草枯致大鼠急性肺损伤治疗作用的实验研究[J].中国呼吸与危重监护杂志, 2007,6(4):290-293.
[8] 姚树桐, 苗成, 刘庆华, 等. 槲皮素预处理对衣霉素所致巨噬细胞凋亡的抑制作用及机制[J].生理学报, 2013,65(1):47-54.
[9] MARCINIAK S J. Endoplasmic reticulum stress in lung disease[J].Eur Respir Rev,2017,26(144):170018.
[10] CHEN X, WANG Y, XIE X, et al. Heme oxygenase-1 reduces sepsis-induced endoplasmic reticulum stress and acute lung injury[J].Mediators Inflamm,2018,9413876, 10.
[11] 杨琦, 曾迎楠, 许永安. 急性肺损伤发病与发展相关信号通路的研究进展[J].国际呼吸杂志, 2020,40(24):1904-1909.
[12] MATTHAY M A, ZEMANS R L, ZIMMERMAN G A, et al. Acute respiratory distress syndrome[J].Nat Rev Dis Primers,2019,5(1):18.
[13] RON D, WALTER P. Signal integration in the endoplasmic reticulum unfolded protein response[J].Nat Rev Mol Cell Biol,2007,8(7):519-529.
[14] BARABUTIS N. Unfolded protein response in lung health and disease[J].Front Med (Lausanne),2020,7(1):344.
[15] 彭娇, 唐旭毛, 王导新. 内质网应激与急性呼吸窘迫综合征的研究进展[J].基础医学与临床, 2019,39(12):1763-1766.
[16] 严一核, 孙雪东, 邢海波, 等. 内质网应激在大鼠急性肺损伤中的意义[J].中华危重症医学杂志(电子版), 2013,6(1):21-26.
[17] KELLNER M, NOONEPALLE S, LU Q, et al. ROS signaling in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)[J].Adv Exp Med Biol,2017,967(1):105-137.
[18] XU D, HU M J, WANG Y Q, et al. Antioxidant activities of quercetin and its complexes for medicinal application[J].Molecules,2019,24(6): 1123.
[19] 黄亮, 季宪飞, 曹春水, 等. 槲皮素对内毒素急性肺损伤的保护作用[J].中华急诊医学杂志, 2004,(2):85-87,146.
[20] 岳雯, 姚树桐, 鲍颖, 等. 槲皮素对毒胡萝卜素诱导的巨噬细胞内质网应激凋亡途径的抑制作用及机制[J].中国病理生理杂志, 2012,28(3):518-523.
[21] WANG L, CHEN J, WANG B, et al. Protective effect of quercetin on lipopolysaccharide-induced acute lung injury in mice by inhibiting inflammatory cell influx[J].Exp Biol Med (Maywood),2014 ,239(12):1653-1662.
[22] SUN Q, HAN W, HU H, et al. Hydrogen alleviates hyperoxic acute lung injury related endoplasmic reticulum stress in rats through upregulation of SIRT1[J].Free Radic Res,2017,51(6): 622-632.
2021, Vol. 38 
