摘要
目的:观察雷公藤多苷对IgA肾病(IgA nephropathy,IgAN)大鼠的肾脏保护作用,并基于核因子κB诱导激酶(nuclear factor kappa B inducing kinase,NIK)/核因子κB抑制物激酶α(nuclear factor kappa B-inducing kinaseα,IKKα)/核转录因子-κB2(nuclear transcription factor-κB2,p52)信号通路探讨作用机制。方法:将42只SD大鼠随机分为空白组10只和造模组32只。造模组大鼠采用牛血清白蛋白(bovine serum albumin,BSA)灌胃、四氯化碳(carbon tetrachloride,CCl 4)皮下注射联合脂多糖(lipopolysaccharide,LPS)尾静脉注射的方法建立IgAN模型。将造模成功的大鼠随机分为模型组、泼尼松组(6.25 mg·kg^(-1))和雷公藤多苷组(9.375 mg·kg^(-1))。各药物组大鼠按照相应剂量灌胃,空白组和模型组大鼠给予生理盐水,每日1次,连续7周。采用全自动生化分析仪检测尿液24 h尿蛋白定量(24 hours urinary total protein,24 h-UTP)、尿红细胞(urinary red blood cell,URBC)、血清谷丙转氨酶(alanine aminotransferase,ALT)、白蛋白(albumin,ALB)、血肌酐(serum creatinine,Scr)、血尿素氮(blood urea nitrogen,BUN)水平。采用ELISA法检测血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)含量,HE染色观察肾脏病理学形态,免疫荧光染色观察肾小球系膜区免疫球蛋白A(immunoglobulin A,IgA)表达水平,Western blot和RT-PCR法检测肾脏NIK、IKKα、P52蛋白和基因表达水平。结果:与空白组比较,模型组大鼠24 h-UTP、URBC、Scr、BUN、TNF-α、IL-1β水平升高(P<0.05),血清ALB水平降低(P<0.05);与模型组比较,泼尼松组、雷公藤多苷组大鼠24 h-UTP、URBC、BUN、TNF-α、IL-1β水平降低(P<0.05),ALB水平升高(P<0.05)。HE染色显示,空白组大鼠肾脏结构无异常;模型组大鼠肾小球系膜细胞增生,肾小管上皮细胞水样变性,伴炎症细胞浸润;泼尼松组、雷公藤多苷组大鼠的上述病理表现较模型组明显减轻。免疫荧光染色显示,�
Objective:To observe the renal protective effect of tripterygium polyglycosides on immunegloblin A nephropathy(IgAN)in rats,and to explore its mechanism based on nuclear factor kappa B-inducing kinase(NIK)/nuclear factor kappa B-inducing kinaseα(IKKα)/nuclear transcription factor-κB2(p52)signaling pathways.Methods:A total of 42 SD rats were randomly divided into a blank group(10 rats)and a molding group(32 rats).Rats in the model group were treated with bovine serum albumin(BSA)by gavage and carbon tetrachloride(CCl4)by subcutaneous injection combined with lipopolysaccharide(LPS)being injected into tail vein to establish IgAN model.The rats with successful model were randomly divided into model group,prednisone group(6.25 mg·kg^(-1))and tripterygium polyglycosides group(9.375 mg·kg^(-1)).The rats in these groups were given drugs with the corresponding dose by gavage,while the rats in the blank group and the model group were given normal saline once a day for 7 weeks.24 hours urinary total protein(24 h-UTP)and urinary red blood cell(URBC)alanine aminotransferase(ALT),albumin(ALB),serum creatinine(Scr)and blood urea nitrogen(BUN)levels were detected by automatic biochemical analyzer.The serum levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by ELISA.The pathological morphology of kidney was observed using HE staining.The expression of immunoglobulin A(IgA)in glomerular mesangial region was observed with immunofluorescence staining.The protein and gene expression levels of NIK,IKKαand P52 were detected by Western blot and RT-PCR.Results:Compared with that of the blank group,the levels of 24 h-UTP,URBC,Scr,BUN,TNF-αand IL-1βin the model group were increased significantly(P<0.05),while the level of serum ALB was decreased significantly(P<0.05).Compared with that of the model group,the levels of 24 h-UTP,URBC,BUN,TNF-αand IL-1βin the prednisone and tripterygium glycosides groups were decreased significantly(P<0.05),while the level of ALB was increased significantly(P<0.05).HE
作者
史慧远
宋纯东
宋珂
陈晨晨
姜浩然
刘倍荧
SHI Huiyuan;SONG Chundong;SONG Ke;CHEN Chenchen;JIANG Haoran;LIU Beiying(Pediatric Hospital of the First Affiliated Hospital to Henan University of Chinese Medicine,Zhengzhou Henan China 450000;School of Pediatrics,Henan University of Chinese Medicine,Zhengzhou Henan China 450046)
出处
《中医学报》
CAS
2024年第8期1754-1760,共7页
Acta Chinese Medicine
基金
国家自然科学基金项目(82074493)
河南省卫生健康委员会国家中医临床研究基地科研专项项目(2022JDZX003)
河南省中医药科学研究重大专项项目(2023ZYZD02)
河南省中医药学科领军人才项目[豫卫中医函(2021)8号]。
