五味子乙素对克雷伯菌引起的重症肺炎大鼠肺组织Nrf2/Keap-1/PGC-1α信号通路的影响

Effect of schisandrin B on NRF2/Keap1/PGC-1αsignaling pathway in lung tissue of rats with severe pneumonia caused by Klebsiella

目的探究五味子乙素(schisandrin B,Sch B)对重症肺炎大鼠肺组织核转录因子E2相关因子2(uclear transcription factor E2 related factor 2,Nrf2)/Kelch样环氧氯丙烷相关蛋白-1(Kelch-like epichlorohydrin-associated protein1,Keap-1)/过氧化物酶体增殖激活受体γ共激活因子-1α(peroxisome proliferator-activated receptorγcoactivator-1,PGC-1α)信号通路的影响。方法先构建重症肺炎大鼠模型,随机分为模型组、Sch B不同剂量组(低、中、高剂量组)和阳性对照组,每组10只,另取10只大鼠作为空白对照组。Sch B低、中、高剂量组分别灌胃给予2.50、5.0、10.0 mg/kg Sch B进行干预,阳性对照组给予大鼠地塞米松1.04 mg/kg灌胃治疗,其余组给予生理盐水,连续14 d。主动脉取血,检测血气指标;分离肺组织,检测其病理学变化、炎症因子水平及通路相关蛋白表达。结果空白对照组大鼠正常饮食、精神状态无异常、肺组织结构清晰。与空白对照组相比,模型组大鼠状态较差,肺组织病理损伤严重,PaCO_(2)值、肿瘤坏死因子α(tumour necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)和白细胞介素1β(interleukin-1β,IL-1β)含量、Keap-1蛋白表达均显著增加(P<0.05),PaO_(2)和SaO_(2)水平、Nrf2和PGC-1ɑ蛋白表达明显降低(P<0.05)。与模型组相比,Sch B低、中、高剂量组大鼠不良症状逐渐缓解,肺组织炎性浸润、肺泡间质水肿逐渐减轻,PaCO_(2)值、TNF-ɑ、IL-6和IL-1β含量、Kelch样环氧氯丙烷相关蛋白-1(Kelch-like epichlorohydrin-associated protein1,Keap-1)蛋白表达均依次降低(P<0.05),PaO_(2)和SaO_(2)值、Nrf2和PGC-1ɑ蛋白表达水平依次增加(P<0.05),Sch B高剂量组与阳性对照组相比,各项指标差异均无统计学意义(P>0.05)。结论Sch B可缓解克雷伯菌引起的重症肺炎大鼠不良症状,可能与激活NRF2/PGC-1α信号通路,降低Keap1蛋白表达有关。

Objective To explore the effect of Schisandrin B(Sch B)on nuclear transcription factor E2-related factor 2(Nrf2)/kelch-like epichlorohydrin-associated protein(Keap-1)/peroxisome proliferation-activated receptorγcoactivator-1α(PGC-1α)signaling pathway in lung tissue of rats with severe pneumonia.Methods A rat model of severe pneumonia was first established and then randomly divided into model group,Sch B low,medium,and high dose groups and positive control group,with 10 rats in each group,and another 10 rats was selected as a blank control group.Sch B low,medium and high dose groups were given intragastrically with 2.50,5.0,10.0 mg/kg Sch B for intervention,the positive control group was given 1.04 mg/kg dexamethasone for intervention,and the rest of groups were given equal volume of normal saline,for 14 consecutive days.Aorta blood was taken to detect blood gas index.Lung tissue was isolated,and pathological changes,inflammatory factors and pathway-related protein expression were detected.Results The rats in the control group had normal diet,no abnormal mental state,and clear lung tissue structure.Compared with the control group,the rats in the model group were in a worse state,with symptoms such as unresponsiveness,sluggishness,and shortness of breath,inflammatory infiltration of the lung tissue,edema of the alveolar interstitium,and thickening of the alveolar wall.The PaCO_(2)value,TNF-α,IL-6 and IL-1βcontents,Keap-1 protein expression all increased significantly(P<0.05),the PaO_(2)and SaO_(2)levels,Nrf2 and PGC-1ɑprotein expression reduced significantly(P<0.05).Compared with the model group,the adverse symptoms of rats in the Sch B low,medium,and high dose groups alleviated gradually,and the inflammatory infiltration of lung tissue and alveolar interstitial edema reduced gradually,the PaCO_(2)value,TNF-ɑ,IL-6 and IL-1βcontents,and Keap-1 protein expression all decreased sequentially(P<0.05),the PaO_(2)and SaO_(2)values,Nrf2 and PGC-1ɑprotein expression levels increased sequentially(P<0.05).The indicators were no significant difference between the Sch B high-dose group and the positive control group(P>0.05).Conclusions Sch B can alleviate the adverse symptoms of severe pneumonia caused by Klebsiella in rats,which may be related to the activation of the NRF2/PGC-1αsignaling pathway and the reduction of Keap1 protein expression.