小檗碱下调NF-κB p65/TGF-β1/CTGF信号通路缓解小鼠肾纤维化损伤  

Effect of berberine on regulating NF-κB p65/TGF-β1/CTGF signaling pathway in reducing renal fibrosis injury in mice

作　　者：李光耀 梁佳敏 靳梦彤 席端 刘鹏 王鹏 王瑞华 刘青青 LI Guang-yao;LIANG Jia-min;JIN Meng-tong;XI Duan;LIU Peng;WANG Peng;WANG Rui-hua;LIU Qing-qing(Linfen Central Hospital,Linfen,Shanxi 041000,China)

机构地区：[1]临汾市中心医院,山西临汾041000

出　　处：《中国药理学通报》2024年第11期2042-2047,共6页Chinese Pharmacological Bulletin

基　　金：临汾市重点研发计划(No 2206);山西省基础研究计划(No 202303021212368);山西省卫生健康委科研课题(No 2022122)。

摘　　要：目的研究小檗碱(berberine,BBR)对单侧输尿管梗阻(unilateral ureteral obstruction,UUO)小鼠的保护作用并探索其可能机制。方法C57BL/6小鼠随机分为假手术组(Sham)、UUO组、(50、100、200 mg·kg^(-1))BBR处理组,每组8只。除Sham组外,其余各组行左侧输尿管结扎,建立UUO模型。造模后,Sham和UUO组小鼠灌胃生理盐水,BBR处理组小鼠分别按照50、100、200mg·kg^(-1) BBR灌胃,处理14 d。生化分析仪检测小鼠血清中肌酐(serum creatinine,Scr)及尿素氮(blood urea nitrogen,BUN)水平;HE、Masson、TUNEL及免疫组织化学染色观察肾组织病理改变;ELISA检测血清中促炎细胞因子的表达;Western blot检测肾脏中NF-κB p65、TGF-β1、CTGF蛋白水平。结果与UUO组相比,BBR组小鼠Scr和BUN水平明显下降;肾病变减轻,间质纤维化减低;血清促炎细胞因子表达水平降低;NF-κB p65、TGF-β1、CTGF表达减少,呈一定剂量依赖性。结论小檗碱具有抑制NF-κB p65/TGF-β1/CTGF信号通路的潜力,可抑制肾脏炎症及纤维化,减轻UUO诱导的肾损伤。Aim To investigate the protective effect of berberine(BBR)on mice with unilateral ureteral obstr-uction(UUO)and explore its mechanism.Methods C57BL/6 mice were randomly divided into the sham group,UUO group,and BBR treatment groups(50,100 and 200 mg·kg^(-1)),with eight mice in each group.Except the sham group,the other groups were subjected to left ureteral ligation to establish the UUO model.After modeling,the mice in the sham and UUO groups were fed normal saline,and the mice in the BBR treatment groups were fed(50,100,200)mg·kg^(-1) BBR by gavage for 14 days,respectively.Biochemical analyzer was employed to detect the levels of serum creatinine(Scr)and blood urea nitrogen(BUN).HE,Masson,TUNEL and immunohistochemical staining were used to observe the pathological changes of renal tissue.ELISA was employed to detect the expression of pro-inflammatory cytokines in renal tissue homogenate.Western blot was used to detect the protein levels of NF-κB p65,TGF-β1 and CTGF in mouse kidney.Results Compared with the UUO group,the levels of Scr and BUN in the BBR group were significantly reduced.Renal injury and interstitial fibrosis were alleviated.The expression of pro-inflammatory cytokines decreased in kidney.The expression of NF-κB p65,TGF-β1 and CTGF decreased.All results showed some degree of dose dependence.Conclusion Berberine has a significant protective effect on unilateral ureteral obstruction mice,and the mechanism may be that BBR has the potential to inhibit NF-κB p65/TGF-β1/CTGF signaling pathway,thus reducing renal inflammation and fibrosis.

关 键 词：小檗碱 UUO 肾纤维化 肾损伤 炎症 NF-κB/TGF-β1/CTGF信号 

分 类 号：R285.5[医药卫生—中药学]