基于SIRT1/NF-κB信号通路探讨川芎嗪改善脂多糖诱导小鼠肾损伤的作用机制  

Exploring the mechanism of TMP in relieving the kidney injury of LPS-induced mice through regulating the SIRT1/NF-κB inflammatory signaling pathway

作　　者：熊秀娟 韩菊 张雨涵 陈瑞 杨健[2] XIONG Xiu-juan;HAN Ju;ZHANG Yu-han;CHEN Rui;YANG Jian(School of Basic Medicine,Hubei University of Medicine,Shiyan 442000,China;Shiyan People's Hospital Affiliated to Hubei University of Medicine,Shiyan 442000,China)

机构地区：[1]湖北医药学院基础医学院,湖北十堰442000 [2]湖北医药学院附属十堰市人民医院,湖北十堰442000

出　　处：《时珍国医国药》2025年第2期253-257,共5页Lishizhen Medicine and Materia Medica Research

基　　金：湖北省教育厅科研项目(Q20232105);湖北医药学院人才启动金项目(2023QDJZR05)。

摘　　要：目的探讨SIRT1/NF-κB信号通路在川芎嗪抗脂多糖诱导小鼠肾损伤中的作用和机制。方法将24只C57BL/6小鼠随机分为4组:Control组、LPS组、TMP组、EX527组。脲酶法和肌氨酸氧化酶法分别检测各组小鼠血清中尿素氮和肌酐水平;酶联免疫吸附测定法(ELISA)检测血浆中IL-1β、IL-6和INF-α水平;HE染色观察小鼠肾组织形态变化;qRT-PCR及Western-blot法检查肾脏组织中SIRT1和NF-κB-p65的表达。结果与Control组比较,LPS组小鼠血清中BUN、Scr、IL-1β、IL-6和INF-α升高(P<0.05),肾小球细胞增生,炎性细胞浸润;肾组织NF-κB及SIRT1表达均显著降低(P<0.05)。与LPS组比较,TMP组血清中BUN、Scr、IL-1β、IL-6和INF-α水平下降(P<0.05);肾脏组织炎性细胞浸润程度及凋亡指数均降低(P<0.05);肾脏组织SIRT1表达升高,NF-κB p65却显著降低(P<0.05)。在TMP治疗基础上给予EX527抑制剂处理后,SIRT1表达较单纯TMP治疗降低,而NF-κB p65却再次升高。结论川芎嗪能够减轻LPS诱导的小鼠急性肾损伤,其机制可能与SIRT1/NF-κB信号通路激活抑制炎症反应有关。Objective To investigate the effect and mechanism of Tetramethylpyrazine(TMP)in treating Lipopolysaccharide(LPS)-induced kidney injury of mice through the SIRT1/NF-κB signaling pathway.Methods A total of 24 C57BL/6 mice were randomly divided into the control group,the LPS group,the TMP group and the EX527 group with 6 mice in each.The serum levels of urea nitrogen and creatinine were respectively detected by the urease method and creatinine oxidase method.The serum levels of IL-1β,IL-6 and INF-α were measured by enzymelinked immunosorbent assay(ELISA).Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL)was used to detect the apoptosis of renal cells in each group.qRT-PCR and Western blot(WB)were used to detect the expressions of SIRT1 and NF-κB-p65 in kidney tissues of mice in each group.Results Compared with the control group,the serum levels of IL-1β,IL-6 and INF-αwere increased(P<0.05),glomerular cell proliferation,inflammatory cell infiltration and the apoptosis indexes were increased(P<0.05).The expressions of SIRT1 and NF-κB-p65 were decreased(P<0.05).Compared with the LPS group,the serum levels of IL-1β,IL-6 and INF-α were decreased(P<0.05),and glomerular cell proliferation,inflammatory cell infiltration and the apoptosis indexes were decreased(P<0.05).The expression of SIRT1 was increased,but NF-κB-p65 was decreased(P<0.05).After treatment with EX527,SIRT1 expression was decreased compared with the TMP group,while NF-κB p65 expression was increased again.Conclusion TMP can alleviate LPS-induced acute kidney injury in mice,and the mechanism may be related to activation of the SIRT1/NF-κB signaling pathway in inhibiting the inflammatory response.

关 键 词：川芎嗪 脂多糖 肾损伤 凋亡 沉默信息调节相关酶1/核转录因子-κB 

分 类 号：R285.5[医药卫生—中药学]