基于内质网应激探讨雷公藤多苷治疗IgA肾病作用机制  

Mechanism of Tripterygium wilfordii Glycosides in the Treatment of IgA Nephropathy Based on Endoplasmic Reticulum Stress

作　　者：宋珂 宋纯东[1,2] 宋丹 张守琳[4] 丁樱[1,2] SONG Ke;SONG Chundong;SONG Dan;ZHANG Shoulin;DING Ying(Pediatric Hospital,The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;College of Pediatrics,Henan University of Chinese Medicine,Zhengzhou 450046,China;Henan University of Chinese Medicine,Zhengzhou 450046,China;Affiliated Hospital of Changchun University of Chinese Medicine,Changchun 130021,China)

机构地区：[1]河南中医药大学第一附属医院儿科医院,郑州450000 [2]河南中医药大学儿科医学院,郑州450046 [3]河南中医药大学,郑州450046 [4]长春中医药大学附属医院,长春130021

出　　处：《世界中医药》2025年第2期246-251,共6页World Chinese Medicine

基　　金：国家自然科学基金面上项目(82074493)——基于“肠-肾轴”探明肾必宁颗粒治疗IgA肾病的分子生物学机制;河南省中医药学科领军人才项目(豫卫中医函〔2021〕8号);河南省卫生健康委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“双一流”创建工程项目(HSRP-DFCTCM-2023-3-07)。

摘　　要：目的:探讨雷公藤多苷(GTW)对IgA肾病(IgAN)大鼠内质网应激-自噬通路的影响。方法:清洁级雄性斯泼累格·多雷(SD)大鼠45只,适应性喂养1周后,分为空白组、模型组、泼尼松组、雷公藤组。除空白组外,其余3组采用联合应用牛血清白蛋白+脂多糖+四氯化碳建立IgAN动物模型。第13周起干预组灌胃给药,给药4周后留取大鼠24 h尿液、尿常规、血液以及肾脏组织。生化检测各组大鼠24 h尿总蛋白定量(24 h-UTP)、尿红细胞计数、血肌酐(SCr)、血尿素氮(BUN)、血白蛋白(ALB);苏木精-伊红(HE)染色光镜观察肾脏病理;免疫荧光判定免疫球蛋白IgA在肾小球系膜区的沉积;蛋白免疫质印迹法、实时聚合酶链反应法检测肾组织中蛋白激酶RNA样ER激酶(PERK)、激活转录因子(ATF)4、CCAAT增强子结合蛋白同源蛋白(CHOP)和mRNA表达水平。结果:与空白组比较,模型组大鼠24 h-UTP、尿红细胞计数、血SCr、BUN显著升高,血ALB降低(P<0.01),肾脏PERK、ATF4、CHOP mRNA和蛋白表达显著升高(P<0.01),肾脏组织病变严重,肾IgA沉积明显;与模型组比较,各干预组大鼠24 h-UTP、尿红细胞计数、血SCr、BUN明显降低,血ALB升高(P<0.01),肾脏PERK、ATF4、CHOP mRNA和蛋白表达明显降低(P<0.01),肾脏病理和IgA沉积明显改善。结论:雷公藤多苷可能通过调控PERK/ATF4/CHOP通路,抑制内质网应激,进而改善上述生化指标,保护肾脏功能,减轻肾脏病理损害。Objective:To investigate the effect of Tripterygium wilfordii glycosides(GTW)on the endoplasmic reticulum stress-autophagy pathway in rats with IgA nephropathy(IgAN).Methods:Forty-five male Sprague-Dawley(SD)rats were acclimated for 1 week and then randomly assigned into four groups:blank group,model group,prednisone group,and GTW group.Except for the blank group,the remaining groups were used to establish the IgAN model by administering a combination of bovine serum albumin,lipopolysaccharide,and carbon tetrachloride.From the 13th week,the intervention groups were given oral administration of their respective treatments for 4 weeks.After the intervention,24-hour urine,urine routine,blood,and kidney tissue were collected.Biochemical tests included measurements of 24-hour urine total protein(24 h-UTP),urine red blood cell count,serum creatinine(SCr),blood urea nitrogen(BUN),and blood albumin(ALB).Hematoxylin-eosin(HE)staining was used to observe kidney pathology.Immunofluorescence determined the deposition of immunoglobulin IgA in the mesangial area of the glomerulus.Protein and mRNA expression levels of protein kinase RNA-like ER kinase(PERK),activating transcription factor(ATF)4,and CCAAT/enhancer-binding protein homologous protein(CHOP)were detected by Western blot and real-time polymerase chain reaction(PCR).Results:Compared with the blank group,the model group showed significantly increased 24 h-UTP,urine red blood cell count,SCr,and BUN,along with a decreased ALB(P<0.01).The mRNA and protein expression of PERK,ATF4,and CHOP was significantly elevated(P<0.01).The kidney tissue had severe lesions,and IgA deposition in the kidney was prominent.Compared with the model group,the intervention groups showed significantly reduced 24 h-UTP,urine red blood cell count,SCr,and BUN,and elevated ALB(P<0.01).The mRNA and protein expression of PERK,ATF4,and CHOP was significantly reduced(P<0.01),and kidney pathology and IgA deposition improved significantly.Conclusion:GTW may protect kidney function and alleviate kidney pat

关 键 词：IGA肾病 雷公藤多苷 内质网应激 系膜增生 免疫荧光 实验研究 作用机制 蛋白激酶R样内质网激酶/转录活化因子4/CCAAT增强子结合蛋白同源蛋白 

分 类 号：R285.5[医药卫生—中药学] R277.5[医药卫生—中医学]