基于RIOK3-铁蛋白自噬轴探讨金叶败毒颗粒对脓毒症肺损伤大鼠的保护作用OA
Protective effects of Jinye Baidu Granules on sepsis-induced lung injury in rats based on the RIOK3-ferritin autophagy axis
目的 探究金叶败毒颗粒改善脓毒症大鼠肺损伤的作用机制.方法 将大鼠随机分为空白组、假手术组、模型组、金叶败毒颗粒组(金叶组,1.28 g/kg)、地塞米松组(地米组,0.27 mg/kg)、金叶败毒颗粒+地塞米松组(金叶+地米组,1.28 g/kg+0.27 mg/kg),每组 6 只,采用盲肠穿刺法构建大鼠脓毒症模型,造模后立即、造模后 8h 分别灌胃给药 1 次.造模 24 h 后处死大鼠,取肺组织,计算肺系数以评估肺水肿情况;比色法检测肺组织中总铁离子、Fe2+、Fe3+及丙二醛(MDA)水平;ELISA 法检测肺组织中白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平;HE 染色观察各组肺组织切片病理变化;RT-qPCR 法检测肺组织 RIOK3、NCOA4 mRNA 表达;Western blot 法检测肺组织铁蛋白重链(FTH1)、LC3B 蛋白表达.结果 与假手术组比较,模型组大鼠肺泡结构明显破坏,肺间质和肺泡内明显水肿,炎症细胞浸润明显,RIOK3、NCOA4 mRNA 表达、LC3B 蛋白表达、Fe2+、MDA、IL-6、TNF-α 水平、肺系数升高(P＜0.01),FTH1 蛋白表达及 Fe3+水平降低(P＜0.01).与模型组比较,各给药组大鼠右肺组织病理损伤均有不同程度改善,肺组织RIOK3、NCOA4 mRNA 表达、LC3B 蛋白表达、Fe2+、MDA、IL-6、TNF-α 水平、肺系数降低(P＜0.05,P＜0.01),FTH1 蛋白表达及 Fe3+水平升高(P＜0.05,P＜0.01),其中以金叶+地米组效果最佳.结论 金叶败毒颗粒可通过抑制 RIOK3-铁蛋白自噬轴改善脓毒症大鼠肺组织的炎症反应、肺水肿和肺上皮细胞损伤,其与地塞米松联合应用效果更佳.
AIM To investigate the mechanism of Jinye Baidu Granules in improving lung injury in septic rats.METHODS Rats were randomly divided into blank group,sham operation group,model group,Jinye Baidu Granules group(Jinye group,1.28 g/kg),dexamethasone group(Dimi group,0.27 mg/kg)and Jinye Baidu Granules+dexamethasone group(Jinye+Dimi group,1.28 g/kg+0.27 mg/kg),with 6 rats in each group.Rat sepsis model was established by cecocentesis,and the drugs were given by gavage once immediately and 8 hours after modeling.Rats were killed 24 hours after modeling,lung tissue was taken and lung coefficient was calculated to evaluate pulmonary edema.The levels of total iron ion,Fe2+,Fe3+and malondialdehyde(MDA)in lung tissue were detected by colorimetry.The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in lung tissue were detected by ELISA.HE staining was used to observe the pathological changes of lung tissue sections in each group.RT-qPCR method was used to detect the mRNA expressions of RIOK3 and NCOA4 in lung tissue.Western blot was used to detect the protein expressions of ferritin heavy chain(FTH1)and LC3B in lung tissue.RESULTS Compared with the sham operation group,the alveolar structure in the model group was obviously destroyed,the interstitial lung and alveoli were obviously edematous,the inflammatory cells were obviously infiltrated,the mRNA expressions of RIOK3 and NCOA4,the protein expression of LC3B,the levels of Fe2+,MDA,IL-6 and TNF-α,the lung coefficient were increased(P＜0.01),and the protein expression of FTH1 and the level of Fe3+were decreased(P＜0.01).Compared with the model group,the pathological injury of the right lung tissue of rats in each treatment group was improved to varying degrees.The mRNA expressions of RIOK3 and NCOA4,the protein expression of LC3B,the levels of Fe2+,MDA,IL-6 and TNF-α,and the lung coefficient were decreased(P＜0.05,P＜0.01),while the protein expression of FTH1 and the level of Fe3+were increased(P＜0.05,P＜0.01),among which Jinye+Dimi group had the best effect.CONCLUSION Jinye Baidu Granules can improve the inflammatory reaction,pulmonary edema and lung epithelial cell injury in septic rats by inhibiting the autophagy axis of RIOK3-ferritin,and its combined application with dexamethasone is more effective.
张雪玲;黄迪;梁明昊;许一飞;邱占军;陈宪海
山东中医药大学第一临 床 医 学 院,山东 济南 250014||山东第一医科大学附属中心医院中医科,山东 济南 250013山东中医药大学附属医院呼吸与危重症医学科,山东 济南 250014山东中医药大学第一临床医学院,山东 济南 250014山东中医药大学第一临床医学院,山东 济南 250014山东中医药大学第一临床医学院,山东 济南 250014||山东中医药大学附属医院呼吸与危重症医学科,山东 济南 250014山东中医药大学第一临床医学院,山东 济南 250014||山东中医药大学附属医院呼吸与危重症医学科,山东 济南 250014
医药卫生
金叶败毒颗粒脓毒症肺损伤RIOK3-铁蛋白自噬轴
Jinye Baidu Granulessepsislung injuryRIOK3-ferritin autophagy axis
《中成药》 2026 (4)
1131-1137,7
国家自然科学基金(82274320)山东省自然科学基金中医药联合基金培育项目(ZR2021LZY027)山东省自然科学基金委员会面上项(ZR2020MH392)
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