落新妇苷对慢性肾功能衰竭大鼠肾损伤的影响及机制  

Effects and mechanism of astilbin on renal injury in chronic renal failure rats

作　　者：高晓卫 刘迎迎[2] 韩聪 郝世飞[3] GAO Xiaowei;LIU Yingying;HAN Cong;HAO Shifei(Dept.of Emergency,the Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250011,China;Dept.of Nephrology,the Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250011,China;Dept.of Rehabilitation Medicine,Shanxi Provincial People’s Hospital,Taiyuan 030012,China)

机构地区：[1]山东中医药大学附属医院急诊科,济南250011 [2]山东中医药大学附属医院肾病科,济南250011 [3]山西省人民医院康复医学科,太原030012

出　　处：《中国药房》2025年第4期434-439,共6页China Pharmacy

基　　金：山东省医药卫生科技发展计划项目(No.2019WS578)。

摘　　要：目的基于Jagged-1/Notch-1信号通路探讨落新妇苷(AST)对慢性肾功能衰竭(CRF)大鼠肾损伤的影响及潜在机制。方法以5/6肾切除术法构建CRF模型,并将造模成功的大鼠随机分为模型组(Model组)、AST低剂量组(AST-L组)、AST高剂量组(AST-H组)、AST高剂量+Notch通路激活剂(Jagged1/FC嵌合蛋白,简称“JFC”)组(AST-H+JFC组),另设开腹不切除的对照组(CK组),每组10只。AST-L组和AST-H组大鼠分别灌胃40、80 mg/kg的AST,AST-H+JFC组大鼠同时灌胃80 mg/kg的AST和0.5 mg/kg的JFC,CK组和Model组大鼠灌胃等体积生理盐水,每天1次,连续4周。末次给药后,检测各组大鼠血清尿素氮(BUN)、血清肌酐(SCr)、24 h尿液尿蛋白(UP)水平以及血清乳酸脱氢酶(LDH)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-10水平;观察其肾组织形态和纤维化情况,检测肾组织线粒体中腺苷三磷酸(ATP)含量和钠钾ATP酶、钙镁ATP酶活性,以及肾组织中转化生长因子β(TGF-β)、低氧诱导因子1α(HIF-1α)、α-平滑肌肌动蛋白(α-SMA)、切割型胱天蛋白酶3(cleavedcaspase-3)、Jagged-1、Notch-1蛋白的表达水平。结果与CK组比较,Model组大鼠肾组织损伤明显,肾组织纤维化严重;其血清BUN、SCr和尿液UP水平,血清LDH、TNF-α、IL-6水平,以及肾组织中TGF-β、HIF-1α、α-SMA、cleaved-caspase-3、Jagged-1、Notch-1蛋白的表达水平均显著升高,血清IL-10水平以及肾组织线粒体中ATP含量和钠钾ATP酶、钙镁ATP酶活性均显著降低(P<0.05)。与Model组比较,AST各剂量组大鼠肾组织损伤和纤维化均有所减轻;其血清BUN、SCr和尿液UP水平,血清LDH、TNF-α、IL-6水平,以及肾组织中TGF-β、HIF-1α、α-SMA、cleaved-caspase-3、Jagged-1、Notch-1蛋白的表达水平均显著降低,血清IL-10水平以及肾组织线粒体中ATP含量和钠钾ATP酶、钙镁ATP酶活性均显著升高,且AST-H组上述指标的变化较AST-L组明显(P<0.05)。JFC可显著逆转高剂量AST对CRF大鼠肾OBJECTIVE To investigate the effect and potential mechanism of astilbin(AST)on renal injury in chronic renal failure(CRF)rats based on the Jagged-1/Notch-1 signaling pathway.METHODS CRF model was constructed by 5/6 nephrotomy.The successfully modeled rats were randomly separated into Model group,AST low-dose group(AST-L group),AST high-dose group(AST-H group),high-dose of AST+Notch pathway activator(Jagged-1/FC chimerin,referred to as“JFC”)group(AST-H+JFC group),and control group(CK group)for open surgery without resection was set up,with 10 rats in each group.The rats in the AST-L group and AST-H group were given 40 and 80 mg/kg AST,respectively;the rats in the AST-H+JFC group were simultaneously given 80 mg/kg AST and 0.5 mg/kg JFC,and the rats in the CK group and Model group were given an equal volume of normal saline,once a day,for 4 weeks.After the last administration,the serum levels of blood urea nitrogen(BUN),serum creatinine(SCr),and the level of 24 h urinary protein(UP)in urine,as well as the serum levels of lactate dehydrogenase(LDH),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-10 in each group were detected.The morphology and fibrosis of renal tissue were observed.The content of adenosine triphosphate(ATP)and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were detected.The protein expressions of transforming growth factor-β(TGF-β),hypoxia-inducible factor-1α(HIF-1α),α-smooth muscle actin(α-SMA),cleaved-caspase-3,Jagged-1 and Notch-1 in renal tissue were also observed.RESULTS Compared with CK group,the renal tissue of rats in the Model group was obviously damaged,renal tissue fibrosis was severe;the serum BUN and SCr levels,urine UP level,serum LDH,TNF-αand IL-6 levels,as well as the protein expressions of TGF-β,HIF-1α,α-SMA,cleaved-caspase-3,Jagged-1 and Notch-1 in renal tissue were significantly increased,while the serum IL-10 level,ATP content and activities of sodium-potassium ATPase and calcium-magnesium ATPase in

关 键 词：落新妇苷 慢性肾功能衰竭 肾损伤 肾纤维化 Jagged-1/Notch-1信号通路 

分 类 号：R965[医药卫生—药理学] R692.5[医药卫生—药学]