Abstract：Objective: To investigate the effects of sufentanil (Sufen) on lung injury in rats with severe pneumonia (SP) and the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) pathway. Methods: An SP rat model was constructed; the successfully modeled rats were grouped into severe pneumonia group (SP group), low-dose and high-dose sufentanil groups (Sufen-L, Sufen-H groups), and high-dose sufentanil+TLR4 activator LPS group (Sufen-H+LPS group), with 24 rats in each group. An additional 24 normal rats were used as the Control group. The levels of inflammatory factors in alveolar lavage fluid and the number of inflammatory cells in alveolar lavage fluid sediment were detected. The wet to dry weight ratio (W/D) of lung tissue was measured. HE staining was applied to observe the pathological changes in lung tissue of rats in each group. Western blot was applied to detect the expression levels of TLR4, MyD88, p-NF-κB p65/NF-κB p65 in lung tissue. Results: The lung tissue in the SP group was more severely damaged than that in the Control group, with thickening of the lung interstitium, alveolar edema, and extensive infiltration of inflammatory cells, the levels of TNF-α, IL-1β, IL-6, numbers of EOS and NEU inflammatory cells, W/D ratio, the protein expression of TLR4, MyD88, and p-NF-κB p65/NF-κB p65 were greatly increased (P<0.05). Compared with the SP group, the Sufen-L and Sufen-H groups showed reduced lung tissue damage, gradually intact alveolar structure, reduced edema, and reduced infiltration of inflammatory cells, the levels of TNF-α, IL-1β, IL-6, numbers of EOS and NEU inflammatory cells, W/D ratio, the protein expression of TLR4, MyD88, and p-NF-κB p65/NF-κB p65 were greatly reduced, and the Sufen-H group was superior to the Sufen-L group (P<0.05). Compared with the Sufen-H group, the Sufen-H+LPS group had more severe lung tissue damage, severe alveolar structural damage, great alveolar edema, and increased inflammatory cell infiltration in rats, the levels of TNF-α, IL-1β, IL-6, numbers of EOS and NEU inflammatory cells, W/D ratio, the protein expression of TLR4, MyD88, and p-NF-κB p65/NF-κB p65 were greatly increased (P<0.05). Conclusion: Sufen improves lung injury in rats with SP and is associated with inhibition of the TLR4/MyD88/NF-κB signaling pathway.
皇甫彪, 张京硕, 叶海宾, 李媛媛. 舒芬太尼调节TLR4/MyD88/NF-kB通路对重症肺炎大鼠肺损伤的影响[J]. 河北医学, 2024, 30(7): 1082-1087.
HUANG Fubiao, ZHANG Jingshuo, YE Haibin, et al. Effect of Sufentanil on Lung Injury in Rats with Severe Pneumonia by Regulating TLR4/MyD88/NF-κB Pathway. HeBei Med, 2024, 30(7): 1082-1087.
[1] Garg M,Johri S,Sagar S,et al.Cardiolipin-mediated PPARγ S112 phosphorylation impairs IL-10 production and inflammation resolution during bacterial pneumonia[J].Cell Rep,2021,34(6):108736-108773. [2] 王学清,李颖,蒋海斌,等.舒芬太尼联合瑞芬太尼静脉麻醉对兔内毒素性急性肺损伤时促炎因子的影响[J].中国医院药学杂志,2019,39(11):1124-1128. [3] Zhu Y,Han Q,Wang L,et al.Jinhua Qinggan granules attenuates acute lung injury by promotion of neutrophil apoptosis and inhibition of TLR4/MyD88/NF-κB pathway[J].Ethnopharmacol,2023,301(1):115763-115772. [4] 卢晶,苑萌,冯学辉,等.白藜芦醇调控ROS/NLRP3/Caspase1通路介导的细胞焦亡对重症肺炎大鼠肺损伤的保护作用[J].分子诊断与治疗杂志,2023,15(5):888-891,896. [5] Hu Q,Wang Q,Han C,et al.Sufentanil attenuates inflammation and oxidative stress in sepsis-induced acute lung injury by downregulating KNG1 expression[J].Mol Med Rep,2020,22(5):4298-4306. [6] Gao Q,Chang N,Liu D.In vitro and in vivo assessment of the protective effect of sufentanil in acute lung injury[J].Int Med Res,2021,49(2):1-11. [7] 何梦,何正光.重症肺炎相关生物标志物的研究进展[J].系统医学,2023,8(20):190-193. [8] 许欣婷,张瑶,陈丽展,等.间充质干细胞中血红素加氧酶-1的过表达抑制NOD样受体热蛋白结构域相关蛋白3炎症小体活化改善大鼠急性肺损伤[J].临床内科杂志,2021,38(11):765-770. [9] 秦玉春,邝向东,蔡林再,等.双氢青蒿素减轻慢性阻塞性肺疾病(COPD)模型大鼠肺损伤[J].基础医学与临床,2023,43(3):427-432. [10] Wang J,Li R,Peng Z,et al.HMGB1 participates in LPS induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2,TLR4 and RAGE/NFκB signaling pathways[J].Int Mol Med,2020,45(1):61-80. [11] Liu L,Zhou L,Wang L,et al.MUC1 attenuates neutrophilic airway inflammation in asthma by reducing NLRP3 inflammasome-mediated pyroptosis through the inhibition of the TLR4/MyD88/NF-κB pathway[J].Respir Res,2023,24(1):255. [12] Gong C,Ma J,Deng Y,et al.S100A9-/- alleviates LPS-induced acute lung injury by regulating M1 macrophage polarization and inhibiting pyroptosis via the TLR4/MyD88/NFκB signaling axis(1)[J].Biomed Pharmacother,2024,172(1):116233-116248. [13] 叶培军,夏傲,葛昀,等.红景天苷对重症肺炎大鼠肺组织损伤的作用及可能机制[J].中华微生物学和免疫学杂志,2023,43(2):130-136.
2024, Vol. 30 
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