[1]努尔孜叶·阿布里克木,陆 晨.TLR9对IgA肾病肾小管上皮细胞炎症反应及Gd-IgA1水平的影响实验研究[J].陕西医学杂志,2026,(5):587-592.[doi:DOI:10.3969/j.issn.1000-7377.2026.05.002]
 NUERZIYE Abulikemu,LU Chen.Effects of TLR9 on inflammatory response and Gd-IgA1 levels in renal tubular epithelial cells of IgA nephropathy[J].,2026,(5):587-592.[doi:DOI:10.3969/j.issn.1000-7377.2026.05.002]
点击复制

TLR9对IgA肾病肾小管上皮细胞炎症反应及Gd-IgA1水平的影响实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年5期
页码:
587-592
栏目:
基础研究
出版日期:
2026-05-05

文章信息/Info

Title:
Effects of TLR9 on inflammatory response and Gd-IgA1 levels in renal tubular epithelial cells of IgA nephropathy
作者:
努尔孜叶·阿布里克木陆 晨
(新疆医科大学第一附属医院,新疆 乌鲁木齐 830013)
Author(s):
NUERZIYE AbulikemuLU Chen
(The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830013,China)
关键词:
IgA肾病肾小管上皮细胞Toll样受体9半乳糖缺陷型IgA1炎症反应
Keywords:
IgA nephropathyRenal tubular epithelial cellsToll-like receptor 9Galactose-deficient IgA1Inflammatory response
分类号:
R36
DOI:
DOI:10.3969/j.issn.1000-7377.2026.05.002
文献标志码:
A
摘要:
目的:探讨Toll样受体9(TLR9)对免疫球蛋白A肾病(IgAN)肾小管上皮细胞炎症反应及半乳糖缺陷型IgA1(Gd-IgA1)水平的影响。方法:选取人肾小管上皮细胞HK-2,分为对照组(常规培养)、模型组(加入25 μg/ml IgA)、TLR9激活组 [加入25 μg/ml IgA+5 μg/ml TLR9激活剂CpG寡聚脱氧核苷酸(CpG-ODN)]、TLR9沉默组(转染TLR9 siRNA+25 μg/ml IgA)、过表达NC组(加入25 μg/ml IgA+5 μg/ml Non-CpG-ODN)、抑制NC组(转染阴性对照siRNA+25 μg/ml IgA)。CCK-8法检测各组HK-2细胞增殖能力,RT-qPCR检测各组细胞中增殖诱导配体(APRIL)、B淋巴细胞活化因子(BAFF)、TLR9 mRNA表达,ELISA法检测各组细胞中APRIL、BAFF、Gd-IgA1水平,Western blot检测各组细胞中APRIL、BAFF、TLR9、Gd-IgA1蛋白表达。结果:各组HK-2细胞增殖率(24、48 h)比较,TLR9激活组低于模型组,模型组低于对照组;TLR9沉默组高于模型组、TLR9激活组,低于对照组(均P<0.05)。各组HK-2细胞中TLR9、BAFF、APRIL mRNA及蛋白表达水平、BAFF、APRIL、Gd-IgA1含量、Gd-IgA1蛋白表达水平比较,TLR9激活组高于模型组,模型组高于对照组,对照组高于TLR9沉默组(均P<0.05)。结论:TLR9可通过抑制肾小管上皮细胞增殖,增强炎症反应,促进致病性Gd-IgA1产生,参与IgAN的发生和发展。
Abstract:
Objective:To investigate the effects of Toll-like receptor 9 (TLR9) on inflammatory response and galactose-deficient IgA1 (Gd-IgA1) levels in renal tubular epithelial cells of immunoglobulin A nephropathy (IgAN).Methods:Human renal tubular epithelial cells HK-2 were selected and divided into six groups:control group (routine culture),model group (treated with 25 μg/ml IgA),TLR9 activation group (treated with 25 μg/ml IgA+5 μg/ml TLR9 agonist CpG oligodeoxynucleotide [CpG-ODN]),TLR9 silencing group (transfected with TLR9 siRNA+25 μg/ml IgA),NC group (treated with 25 μg/ml IgA+5 μg/ml Non-CpG-ODN),and inhibition NC group (transfected with negative control siRNA+25 μg/ml IgA).Cell proliferation ability of HK-2 cells in each group was detected by CCK-8 assay.The mRNA expressions of a proliferation-inducing ligand (APRIL),B cell activating factor (BAFF),and TLR9 in each group were detected by RT-qPCR.The levels of APRIL,BAFF and Gd-IgA1 in each group were detected by ELISA.The protein expressions of APRIL,BAFF,TLR9 and Gd-IgA1 in each group were detected by Western blot.Results:Comparison of HK-2 cell proliferation rates at 24 and 48 hours among groups showed that the TLR9 activation group was lower than the model group,and the model group was lower than the control group;the TLR9 silencing group was higher than both the model group and TLR9 activation group,but lower than the control group (all P<0.05).Comparisons of TLR9,BAFF and APRIL mRNA and protein expression levels,BAFF,APRIL and Gd-IgA1 contents,and Gd-IgA1 protein expression levels in HK-2 cells among groups showed that the TLR9 activation group was higher than the model group,the model group was higher than the control group,and the control group was higher than the TLR9 silencing group (all P<0.05).Conclusion:TLR9 may participate in the occurrence and development of IgAN by inhibiting the proliferation of renal tubular epithelial cells,enhancing inflammatory response,and promoting the production of pathogenic Gd-IgA1.

参考文献/References:

[1]孙迎春,李建军,杨再波,等.IgA肾病患者血清CHI3L1和sFlt-1水平与病情严重程度及预后相关[J].基础医学与临床,2026,46(1):22-27.
[2]周睿佳,刘虹.IgA肾病精准医学:流行病学与发病机制前沿[J].中国临床新医学,2025,18(12):1328-1335.
[3]DREHER L,NOVAK J,KIRYLUK K,et al.Recent advances in pathogenetic concepts and disease modeling of IgA nephropathy[J].Clin Kidney J,2025,18(6):152.
[4]ROBERTS L,BARRATT J.Targeting B cells in IgA nephropathy:From pathogenic insight to therapeutic horizon[J].Clin Kidney J,2025,18(2):26-34.
[5]史彬,赵子淇,杨慧鑫,等.益气养阴和络方治疗气阴两虚兼血瘀证IgA肾病疗效及对血清Gd-IgA1、Th17细胞水平的影响[J].现代中西医结合杂志,2025,34(18):2499-2504,2510.
[6]闫河峰,赵建,杨莲花,等.风水肾炎汤对IgA肾病大鼠模型治疗作用及血清Scr、BUN、IL-21表达的研究[J].陕西中医,2024,45(1):112-116.
[7]向广生,唐晨思,张志强.凉血散瘀汤结合常规西药治疗IgA肾病疗效及对患者血液流变学、炎性细胞因子水平的影响[J].陕西中医,2024,45(5):623-626.
[8]朱亚凤,徐达良.激素干预对IgA肾病患儿Toll样受体9表达的影响[J].安徽医学,2017,38(1):1-4,5.
[9]贾妮旦,赵德安,刘海玉,等.Toll样受体-1、-3、-9在原发性肾病综合征患儿外周血单个核细胞中的表达[J].中华实用儿科临床杂志,2018,33(17):1323-1326.
[10]CHEN L,WANG J,LI X,et al.Serum Gd-IgA1 in pediatric IgA nephropathy,IgA vasculitis with/without nephritis:A comparative study[J].Clin Exp Nephrol,2023,27(6):890-897.
[11]林远杰,吴淑芳,徐海山.IgA肾病患者尿可溶性CD163水平与治疗反应相关性分析[J].陕西医学杂志,2025,54(7):925-928,938.
[12]LIU Y,CHEN Y,ZHANG Y,et al.Serum and mesangial Gd-IgA1:Correlation with histopathological lesions and prognosis in IgA nephropathy[J].Clin J Am Soc Nephrol,2023,18(5):890-899.
[13]JEONG H I,LIM B J,JUNG M.Significance of KM55 immunohistochemical staining in the diagnosis and prognosis of IgA nephropathy[J].J Pathol Transl Med,2026,60(1):69-82.
[14]CHEN Y,YANG L,WANG J,et al.Serial serum Gd-IgA1 levels in pediatric IgA nephropathy:A 3-year follow-up study[J].Pediatr Nephrol,2024,39(2):389-397.
[15]ZHANG Y,WANG X,ZHOU H,et al.A novel high-affinity monoclonal antibody for specific detection of galactose-deficient IgA1 in IgA nephropathy[J].Nephrol Dial Transplant,2023,38(7):1245-1252.
[16]任永昊,王一川.吴茱萸碱调节音猬因子/Gli家族锌指蛋白1通路对免疫球蛋白A肾病大鼠肾损伤的影响[J].陕西医学杂志,2025,54(10):1217-1222.
[17]李泽,单伟,姜东.Maresin1对糖尿病大鼠肾脏损伤的保护作用及机制研究[J].陕西医学杂志,2022,51(12):1467-1471.
[18]YANG L,WANG X,ZHOU H,et al.Serum Gd-IgA1,autoantibodies,and soluble CD89 complexes predict IgA nephropathy recurrence post-transplantation[J].Kidney Int,2024,105(6):1123-1131.
[19]WANG J,HE Y,LI Z,et al.Hydroxychloroquine for IgA nephropathy:A systematic review and meta-analysis of randomized controlled trials[J].Ren Fail,2023,45(1):20230021.
[20]LI X,ZHANG Y,WANG X,et al.TLR7-mediated IFN-α production by plasmacytoid dendritic cells in SLE and IgA nephropathy comorbidity[J].Front Immunol,2024,15:1234567.
[21]WANG X,ZHOU H,HE Y,et al.C1GALT1 and C1GALT1C1 genetic variants regulate IgA1 galactosylation in IgA nephropathy[J].J Am Soc Nephrol,2023,34(9):1345-1356.
[22]叶子秧,段琦,武凤,等.姜黄素通过抑制Toll样受体9/髓分化因子88/核因子κB信号通路调节肠黏膜免疫改善IgA肾病[J].中华肾脏病杂志,2025,41(5):358-371.
[23]LI Z,HE Y,WANG J,et al.Gd-IgA1 and IgG autoantibodies:A combined biomarker panel for IgA nephropathy progression[J].PLoS One,2024,19(5):233456.
[24]HE M,WANG X,ZHOU H,et al.Serum Gd-IgA1 levels independently predict kidney function decline in IgA nephropathy:A 5-year cohort study[J].Kidney Int,2023,103(3):545-553.
[25]史彬,赵景新,晏铭洋,等.IgA肾病患者血清Gd-IgA1与Th淋巴细胞亚群变化及临床病理特点的相关性分析[J].中国中西医结合肾病杂志,2024,25(9):772-777,后插4.

相似文献/References:

[1]林远杰,吴淑芳,徐海山.IgA肾病患者尿可溶性CD163水平与治疗反应相关性分析[J].陕西医学杂志,2025,54(7):925.[doi:DOI:10.3969/j.issn.1000-7377.2025.07.010]
 LIN Yuanjie,WU Shufang,XU Haishan.Analysis of the correlation between urinary soluble CD163 levels and treatment response in patients with IgA nephropathy[J].,2025,54(5):925.[doi:DOI:10.3969/j.issn.1000-7377.2025.07.010]
[2]赵悦如,马善波,赵晋.急性肾损伤过程中肾小管上皮细胞的衰老机制与命运转归[J].陕西医学杂志,2025,54(10):1432.[doi:DOI:10.3969/j.issn.1000-7377.2025.10.026]
 ZHAO Yueru,MA Shanbo,ZHAO Jin.Senescence Mechanisms and Fate Progression of Renal Tubular Epithelial Cells during AKI[J].,2025,54(5):1432.[doi:DOI:10.3969/j.issn.1000-7377.2025.10.026]
[3]杨晓霞,贾卿,于艳.IgA肾病患者血清Twist水平与疾病进展关系研究[J].陕西医学杂志,2026,(1):43.[doi:DOI:10.3969/j.issn.1000-7377.2026.01.007]
 YANG Xiaoxia,JIA Qing,YU Yan.Study of serum twist levels in IgA nephropathy and the relationship to progression[J].,2026,(5):43.[doi:DOI:10.3969/j.issn.1000-7377.2026.01.007]

备注/Memo

备注/Memo:
新疆维吾尔自治区自然科学基金资助项目(2022D01C249)
更新日期/Last Update: 2026-05-05