摘要
目的探索连翘苷调节单磷酸腺苷活化蛋白激酶(AMPK)/沉默信息调节因子1(SIRT1)/核因子-κB(NF-κB)通路对呼吸道合胞病毒(RSV)感染大鼠肺组织炎性损伤的影响。方法通过鼻腔滴入RSV Long株法建立RSV感染大鼠模型,并将其分为模型组、连翘苷组(200mg/kg)、连翘苷+抑制剂组(200mg/kg连翘苷和250μg/kg Compound C),另外将鼻腔滴入等量生理盐水的大鼠作为对照组,每组12只;测定各组大鼠肺指数;血气分析仪分析各组大鼠血液PaO_(2)、SaO_(2)及PaCO_(2)含量;ELISA试剂盒测定肺组织IL-1β、TNF-α及IL-8水平;HE染色法观察各组大鼠肺组织形态结构变化;Western blot法测定各组大鼠肺组织NF-κB p65、磷酸化(p)-NF-κB p65、AMPK、P-AMPK和SIRT1蛋白表达情况。结果对照组大鼠肺组织结构正常,无炎性细胞浸润现象;与对照组相比,模型组大鼠肺泡壁上皮细胞损伤严重,且肺间质炎性细胞浸润较多,肺泡间隔增厚明显,肺指数和PaCO_(2)水平上升,肺组织中IL-1β、TNF-α和IL-8水平以及p-NF-κB p65蛋白表达量增加,但PaO_(2)、SaO_(2)水平降低,P-AMPK、SIRT1蛋白表达量下降(P<0.05);与模型组相比,连翘苷组大鼠肺组织病理损伤明显减轻,肺指数降低,PaCO_(2)水平、肺组织IL-1β、TNF-α和IL-8水平以及p-NF-κB p65蛋白表达量减少,而PaO_(2)和SaO_(2)水平升高,P-AMPK和SIRT1蛋白表达量增加(P<0.05);使用AMPK抑制剂干预后,可逆转连翘苷对RSV感染大鼠上述指标的改善作用(P<0.05)。结论连翘苷可能通过激活AMPK/SIRT1/NF-κB通路减轻RSV感染大鼠肺组织炎性损伤。
Objective To explore the effect of phillyrin on lung tissue inflammatory injury in rats infected with respiratory syncytial virus(RSV)by regulating the adenosine monophosphate activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/nuclear factor-kappa B(NF-κB)pathway.MethodsThe RSV infection rat model was established by intranasal instillation of RSV Long strain,which was grouped into model group,phillyrin group(200 mg/kg),phillyrin+inhibitor group(200 mg/kg phillyrin and 250 g/kg Compound C).In addition,rats with an equal amount of physiological saline into their nasal cavities were used as a control group,each with 12 rats.The lung index of rats in each group was measured.The blood gas analyzer was used to analyze the PaO_(2),SaO_(2),and PaCO_(2)in the blood of each group.ELISA kits were used to measure the IL-1p,TNF-α,and IL-8 in lung tissue.HE staining method was used to observe the morphological changes of lung tissue of rats.Western blot was used to determine the NF-sB p65,phosphorylated(p)-NF-κB p65,AMPK,p-AMPK,and SIRT1 proteins in lung tissues of rats in each group.Results The lung tissue structure of rats in the control group was normal,with no inflammatory cell infiltration.Compared with the control group,the model group showed severe damage to the alveolar wall epithelial cells,increased infiltration of inflammatory cells in the lung interstitium,prominent thickening of alveolar septa,increased lung index and PaCO_(2).increased lung tissue IL-1p,TNF-α,IL-8,and p-NF-B p65 protein,decreased PaO_(2)and SaO_(2),and the p-AMPK and SIRT1 proteins(P<O.05).Compared with the model group,the phillyrin group showed a prominent reduction in pathological damage to rat lung tissue,decreased lung index,decreased PaCO_(2),lung tissue IL-1p,TNF-α,and IL-8,and p-NF-κB p65 protein,the levels of PaO_(2),SaO_(2)increased,and the expression levels of p-AMPK and SIRT1 proteins increased(P<0.O5).AMPK inhibitor intervention could reverse the improvement effect of phillyrin on the above indicators in RSVinfected rats(P<0.05).ConclusionPIhillyrin may alleviate lung tissue inflammatory damage in RSV infected rats by activating AMPK/SIRT1/NF-κB pathway.
作者
潘铖铖
李艳冰
PAN Chengcheng;LI Yanbing(Department of Otorhinolaryngology,Shengjing Hospital Affiliated to China Medical University,Shenyang 110000,China)
出处
《中国病原生物学杂志》
北大核心
2025年第10期1270-1274,共5页
Journal of Pathogen Biology
