摘要
目的 基于炎症相关通路探讨雷公藤多苷片对IgA肾病大鼠肾脏的作用机制。方法 雄性SPF级SD大鼠,随机分为空白组、造模组。造模组采用联合“牛血清白蛋白+四氯化碳+脂多糖”建立IgA肾病大鼠模型。造模成功的大鼠随机分为模型组、泼尼松组、雷公藤多苷片组,于第13周开始治疗组灌胃给药,给药4周后留取大鼠24 h尿液、血液、肾组织并检测尿红细胞数、24 h-UTP、BUN、Scr;ELISA检测血清IL-1β、TNF-α水平;HE染色观察各组大鼠肾组织病理学变化;Western blot及RT-PCR检测大鼠肾组织LIGHT、HVEM、LTβR蛋白及其mRNA的表达。结果 雷公藤多苷片明显降低IgA肾病大鼠尿红细胞数、24 h-UTP、BUN、Scr水平,改善肾组织病理,降低血清炎症因子IL-1β、TNF-α水平,降低肾组织中LIGHT、HVEM、LTβR蛋白及其mRNA表达水平。结论 雷公藤多苷片可能通过下调LIGHT-HVEM/LTβR信号通路,抑制免疫反应,减少炎症因子释放,从而减轻炎症反应,降低尿红细胞及尿蛋白,改善肾脏病理损伤,保护肾功能。
Aim To explore the mechanism of action of Tripterygium glycosides tablets on kidney of rats with IgA nephropathy based on inflammation-related pathways.Methods Forty-five male SD rats of SPF grade were randomly divided into control group and modeling group.In addition to the blank group,the modeling group used the combination of bovine serum albumin(BSA)+carbon tetrachloride(CCl 4)+lipopolysaccharide(LPS)to establish the IgA nephropathy rat model.Successfully modeled rats were randomly divided into the model group,the prednisone group and Tripterygium glycosides tablets group,and the treatment group was given the drug by gavage from the 13th week,and the 24 hours urine,blood and kidney tissues of the rats were collected and examined after 4 weeks of the administration of the drug.Urine erythrocyte count,quantitative 24-h urine protein(24 h-UTP),urea nitrogen(BUN),and blood creatinine(Scr)were detected in each group;serum interleukin 1β(IL-1β)and tumor necrosis factorα(TNF-α)were detected by enzyme-linked immunosorbent assay(Elisa);the pathological changes in the renal tissues of the rats in each group were observed by horizontal hematoxylin-eosin(HE)staining;and the renal tissues in each group were observed by Western blotting.The expressions of LIGHT,HVEM,LTβR proteins and their mRNAs in rat kidney tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction(RT-PCR).Results Tripterygium glycosides tablets significantly reduced the levels of urinary erythrocyte count,24 h-UTP,BUN,and Scr in IgA nephropathy rats(P<0.01),improved renal histopathology,lowered the levels of serum inflammatory factors IL-1βand TNF-α(P<0.01),and lowered the levels of LIGHT,HVEM,LTβR proteins and their mRNA expression in renal tissues(P<0.01).Conclusions Tripterygium glycosides tablets may inhibit the immune response and reduce the release of inflammatory factors by down-regulating the LIGHT-HVEM/LTβR pathway,thus reducing the inflammatory response,lowering the urinary erythrocytes and
作者
王旭
方虹
樊艳敏
季晗舒
宋珂
陈晨晨
卜继常
丁樱
宋纯东
WANG Xu;FANG Hong;FAN Yan-min;JI Han-shu;SONG Ke;CHEN Chen-chen;BU Ji-chang;DING Ying;SONG Chun-dong(Pediatric Hospital,The First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450099,China;The School of Pediatrics,Henan University of Traditional Chinese Medicine,Zhengzhou 450046,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2024年第12期2277-2282,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金面上项目(No 82074493)
河南省中医药学科领军人才项目[豫卫中医函(2021)8号]
河南省卫健委国家中医临床研究基地科研专项(2022JDZX003)
河南省中医药科学研究重大专项(2023ZYZD02)。
