黄芪葛根汤保护小鼠缺血再灌注急性肾损伤的机制研究  

Mechanism Investigation of Astragalus Puerariae Decoction on Acute Kidney Injury Induced by Ischemia/Reperfusion in Mice

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作  者:高铂阳 邵方滨 夏琼璋 王永飚[2] GAO Boyang;SHAO Fangbing;XIA Qiongzhang;WANG Yongbiao(Alberta Institute,Wenzhou Medical University,Wenzhou 325035,China;The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区:[1]温州医科大学阿尔伯塔学院,浙江温州325035 [2]温州医科大学附属第二医院/育英儿童医院,浙江温州325000

出  处:《中国中医基础医学杂志》2025年第4期644-648,共5页JOURNAL OF BASIC CHINESE MEDICINE

基  金:浙江省医药卫生科技计划项目(2020KY645);温州科技局计划项目(Y20190085)。

摘  要:目的探究黄芪葛根汤(Astragalus Pueraria Decoction,APD)对小鼠缺血再灌注(IR)诱导的急性肾损伤的保护作用及机制。方法32只C57BL/6J小鼠随机分为假手术组、黄芪葛根汤对照组、缺血再灌注组和黄芪葛根汤治疗组,每组各8只。通过双侧肾蒂夹闭再复通构建小鼠缺血再灌注急性肾损伤模型。黄芪葛根汤治疗组在夹闭双侧肾蒂术前72、48、24h通过灌胃给予每只小鼠1mL APD;黄芪葛根汤对照组小鼠在同时间点给予同等剂量APD。检测各组小鼠血尿素氮(BUN)和肌酐(Scr)水平;HE染色观察肾脏组织病理学改变;流式细胞术检测肾脏淋巴细胞浸润;ELISA法检测血清炎症因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α及核因子κB p65亚基(NF-κB p65)水平;TUNEL法检测肾小管上皮细胞凋亡情况;Western blot检测NF-κB p65、磷酸化NF-κB p65(NF-κB p-p65)水平。结果与假手术组比较,缺血再灌注组小鼠BUN和SCr显著升高,肾小管正常结构破坏,T淋巴细胞浸润显著升高,肾小管上皮细胞的凋亡率显著上升,NF-κB p65与NF-κB p-p65水平上调,以上差异均有统计学意义(P<0.05)。与缺血再灌注组比较,APD处理后上述指标均出现明显改善(P<0.05)。结论APD可通过下调NF-κB信号通路抑制炎症反应及肾小管上皮细胞凋亡,发挥对缺血再灌注肾损伤的保护作用。Objective To investigate the protective effects and mechanisms of Astragalus Puerariae decoction(APD)on ischemia/reperfusion(IR)-induced acute kidney injury(AKI)in mice.Methods 32 C57BL/6J mice were randomly divided into sham,APD,IR,and IR+APD group,with 8 mice in each group.Mouse model of IR induced acute kidney injury was constructed by bilateral renal pedicle occlusion and reperfusion.IR+APD group mice were given 1 mL APD by gavage 72,48,and 24 hours before bilateral renal pedicle occlusion surgery.The APD group mice were given the same dose of APD at the same time point.Renal function was evaluated by detecting BUN and SCr.Pathological changes of kidney were evaluated using HE staining.Flow cytometry was used to detect renal lymphocyte infiltration.The inflammatory cytokines IL-1β,IL-6,TNF-αand NF-κB p65 were evaluated using ELISA.Cell apoptosis of tubular epithelial cells was detected using TUNEL.Western blot was used to detect the levels of NF-κB p65 and phosphorylated NF-κB p65(NF-κB p-p65).Results Compared with the sham group,rats in IR group showed significant increases in BUN and SCr levels,disruption of normal renal tubular structure,significant increase in T lymphocyte infiltration and apoptosis rate of renal tubular epithelial cells,and upregulation of NF-κB p65 and NF-κB p-p65 levels(P<0.05).Compared with IR group,APD treatment significantly improved the indicators above(P<0.05).Conclusion APD may protect renal function from IR-induced tubular epithelial cell apoptosis by inhibiting inflammatory response and lymphocyte infiltration through NF-κB pathway.

关 键 词:黄芪葛根汤 缺血再灌注 急性肾损伤 凋亡 核因子κB p65亚基 

分 类 号:R259[医药卫生—中西医结合] R285[医药卫生—中医内科学]

 

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