蓝萼甲素调节HMGB1/TLR4/NF-κB信号通路对克雷伯菌肺炎大鼠炎性损伤的影响  

Influence of glaucocalyxin A on inflammatory injury in rats with Klebsiella pneumonia by regulating HMGB1/TLR4/NF-κB signaling pathway

作　　者：李柏新[1] 冷晓雪 陈之光[2] LI Bai-xin;LENG Xiao-xue;CHEN Zhi-guang(Shengjing Hospital Rehabilitation Center,Chinese Medical Sciences University,Shenyang110100,China;Emergency Department of Shengjing Hospital,Chinese Medical Sciences University)

机构地区：[1]中国医科大学附属盛京医院康复中心,辽宁沈阳110100 [2]中国医科大学附属盛京医院急诊科

出　　处：《中国病原生物学杂志》2022年第12期1387-1391,共5页Journal of Pathogen Biology

摘　　要：目的研究蓝萼甲素(GLA)对高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)/核转录因子(NF-κB)信号通路的调节作用,探讨其减轻克雷伯菌肺炎大鼠炎性损伤的作用机制。方法将SD大鼠分为正常对照组(NC组)、模型组(M组)、GLA低剂量组(10 mg/kg组)、GLA中剂量组(20 mg/kg组)、GLA高剂量组(40 mg/kg组)和左氧氟沙星组(10 mg/kg),每组10只。通过将克雷伯菌注入气管建立大鼠肺炎模型。造模成功第2 d开始给药,连续7 d。将小鼠处死,取左肺组织称重,计算干重/湿重;HE、TUNEL染色观察肺组织病理变化及细胞凋亡情况;ELISA检测血清中白介素-6(IL-6)、IL-1β、肿瘤坏死因子-α(TNF-α)含量;Western blot检测肺组织HMGB1、TLR4、NF-κB p65蛋白表达。结果与NC组相比,M组小鼠肺组织出现肺泡塌陷、肺泡壁厚度增加等病理现象,W/D值、肺细胞凋亡率、cleaved-caspase3、cleaved-caspase9蛋白水平、IL-6、TNF-α、IL-1β含量及HMGB1、TLR4、NF-κB p65蛋白水平均显著上升(均P<0.05);与M组相比,GLA低、中、高剂量组和左氧氟沙星组肺组织损伤减轻,W/D值、肺细胞凋亡率、cleaved-caspase3、cleaved-caspase9蛋白水平,IL-6、TNF-α、IL-1β含量及HMGB1、TLR4、NF-κB p65蛋白水平均显著下降(均P<0.05)。结论GLA可减轻机体炎性损伤,改善克雷伯菌感染引发的肺炎病情,其机制可能与抑制HMGB1/TLR4/NF-κB信号通路有关。Objective To investigate the regulatory effect of glaucocalyxin A(GLA) on high mobility group box protein B1(HMGB1)/Toll-like receptor 4(TLR4)/nuclear transcription factor(NF-κB) signaling pathway,and to explore its mechanism of reducing inflammatory injury in rats with Klebsiella pneumonia.Methods SD rats were separated into normal control group(NC group),model group(M group),low GLA(10 mg/kg) group,middle GLA(20 mg/kg) group,and high GLA(40 mg/kg) group.group,and positive group(10 mg/kg levofloxacin),10 in each group.A rat pneumonia model was established by instilling Klebsiella into the trachea.Dosing was started on the second day after successful modeling,and continued for 7 days.The mice were killed,the left lung tissue was weighed,and the dry weight/wet weight was calculated;HE and TUNEL staining were applied to observe the pathological changes and apoptosis of lung tissue;ELISA was applied to detect serum levels of interleukin-6(IL-6),IL-1β,and tumor necrosis factor-α(TNF-α);Western blot was applied to detect the protein expression of HMGB1,TLR4,and NF-κB p65 in lung tissue.Results Compared with the NC group,pathological phenomena such as alveolar collapse and increased alveolar wall thickness occurred in the lung tissue of the M group,the W/D value,lung cell apoptosis rate,the protein levels of cleaved-caspase3 and cleaved-caspase9,the levels of IL-6,TNF-α and IL-1β,and the protein levels of HMGB1,TLR4 and NF-κB p65 were obviously increased(P<0.05);compared with the M group,the lung tissue damage in the GLA low,medium and high dose groups and the positive drug group was reduced,the W/D value,lung cell apoptosis rate,the protein levels of cleaved-caspase3 and cleaved-caspase9,the levels of IL-6,TNF-α and IL-1β,and the protein levels of HMGB1,TLR4 and NF-κB p65 were obviously decreased(P<0.05).Conclusion GLA can reduce the inflammatory injury and ameliorate the pneumonia caused by Klebsiella infection,and its mechanism may be related to the inhibition of HMGB1/TLR4/NF-κB signaling pathway.

关 键 词：蓝萼甲素 克雷伯菌肺炎 炎性损伤 HMGB1/TLR4/NF-κB通路 

分 类 号：R378[医药卫生—病原生物学]