汉黄芩苷对IgA肾病大鼠NF-κB/NLRP3通路及系膜增生的影响-现代医学

汉黄芩苷对IgA肾病大鼠NF-κB/NLRP3通路及系膜增生的影响

单位：陕西省人民医院肾病血透中心, 陕西西安 710068

关键词：汉黄芩苷免疫球蛋白A肾病大鼠系膜增生核因子-kappa B/核苷酸结合寡聚化结构域样受体蛋白3通路

分类号：R692.9

出版年·卷·期（页码）：2022·50·第八期（940-945）

摘要：

目的：探讨汉黄芩苷(wogonoside，WG)对免疫球蛋白A肾病(immunoglobulin A nephropathy，IgAN)大鼠系膜增生及核因子-kappa B(nuclear factor-kappa B，NF-κB)/核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3，NLRP3)通路的影响。方法：牛血清白蛋白灌胃联合四氯化碳与脂多糖注射建立IgAN大鼠模型。模型成功后随机分为模型组、WG(低、中、高)剂量组、地塞米松组，每组8只；另设对照组。检测血清肌酐(serum creatinine，SCr)、血尿素氮(blood urea nitrogen，BUN)水平,24 h尿蛋白(24 hour urinary protein，24-UTP)和24 h尿红细胞数，肾脏组织形态，肾脏组织中NF-κB、NLRP3、接头蛋白ASC(apoptosis-associated speck-like proteincontain a caspase activation and recruitment domain，ASC)、半胱氨酸天冬氨酸蛋白酶酶原(cysteine-containing aspartate-specific-3 proteases，pro-caspase-1)、血清中白介素(interleukin，IL)-1β、肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)水平。结果：与对照组相比，模型组肾小球系膜及基质细胞增生严重、炎症明显、荧光聚集，SCr、BUN、24-UTP水平、24 h尿红细胞数、肾脏组织中核内NF-κB、核内NF-κB/总NF-κB、NLRP3、ASC、pro-caspase-1、caspase-1蛋白、血清中IL-1β、TNF-α水平升高(P＜0.05)；肾脏组织中核外NF-κB蛋白水平降低(P＜0.05)。与模型组相比，WG剂量组肾小球系膜及基质细胞增生减弱，荧光强度减弱，肾脏组织中核外NF-κB蛋白水平升高(P＜0.05)，SCr、BUN、24-UTP水平、24 h尿红细胞数、肾脏组织中核内NF-κB、核内NF-κB/总NF-κB、NLRP3、ASC、pro-caspase-1、caspase-1蛋白、血清中IL-1β、TNF-α水平降低(P＜0.05)，呈剂量依赖效应。结论：WG可抑制NF-κB/NLRP3通路实现对IgAN系膜增生的缓解。

Objective: To investigate the effects of wogonide (WG) on mesangial proliferation and nuclear factor kappa B (NF-κB)/nucleotide binding oligomerization domain like receptor protein 3(NLRP3) pathway in rats with immunoglobulin A nephropathy (IgAN).Methods: IgAN rat model was established by gavage of bovine serum albumin combined with carbon tetrachloride and lipopolysaccharide injection.After the establishment of the model,they were randomly divided into model group,WG (low,medium,high) dose group and dexamethasone group,with 8 rats in each group,and the control group was set up.Serum creatinine (SCr),blood urea nitrogen (BUN),24 hour urinary protein (24-UTP),24 hour urinary red blood cells,renal tissue morphology,NF-κB,NLRP3,ASC (aspartate containing aspartate specific-3) in kidney tissue were detected,the levels of pro-caspase-1,IL-1 β and TNF-α in serum were measured.Results: Compared with the control group,glomerular mesangium and stromal cells heavily proliferated,inflammation was obvious,fluorescence gathered in the model group,while the level of SCr,BUN,24-UTP,24 hour the number of urinary red blood cells,nuclear NF-κB,nuclear/total NF-κB,NLRP3,ASC,pro-caspase-1,caspase-1 protein,serum IL-1 β,TNF-α levels in the model group were increased (P <0.05),and the level of extranuclear NF-κB protein in kidney tissue was decreased (P<0.05).Compared with the model group,glomerular mesenteric and stromal cells proliferation decreased,fluorescence intensity decreased in WG dose group (P<0.05),the level of extranuclear NF-κB protein in kidney tissue increased,while the level of SCr,BUN,24-UTP,24 hour the number of urinary red blood cells,nuclear NF-κB,nuclear/total NF-κB,NLRP3,ASC,pro-caspase-1,caspase-1 protein,IL-1 β and TNF-α in serum were decreased (P<0.05),and in a dose-dependent manner.Conclusions:WG can inhibit NF-κB/NLRP3 pathway and alleviate IgAN mesangial hyperplasia.

参考文献：

[1] 蔡香香,程高飞,王萍.益气清解方对治疗高危IgA肾病患者Scr,eGFR,UTP变化的影响[J].中国中西医结合肾病杂志,2020,21(3):230-232.
[2] 申云富,范小青.汉黄芩苷的药理活性研究进展[J].上海中医药大学学报,2016,30(4):98-101.
[3] 胡玲,周乐汀,王思思,等.miR-101靶向mTOR信号通路调控足细胞自噬在小鼠糖尿病肾病发病中的作用研究[J].东南大学学报(医学版),2021,186(2):214-219.
[4] WU C Y,HUA K F,HSU W H,et al.IgA nephropathy benefits from compound k treatment by inhibiting NF-κB/NLRP3 inflammasome and enhancing autophagy and SIRT1[J].J Immunol,2020,205(1):202-212.
[5] 张静,李静,桑晓红,等.运用两种BSA剂量建立IgA肾病大鼠模型观察[J].中国中西医结合肾病杂志,2013,14(1):13-16.
[6] 张玉霞,朱海东.山茱萸总甙对IgA肾病大鼠血清白细胞介素-18、转化生长因子-β1水平及肾组织病理变化的影响[J].中华实用儿科临床杂志,2018,33(17):1327-1331.
[7] 窦一田,杨洪涛,林燕,等.曹式丽运用中医药治疗IgA肾病验案二则[J].中国中医基础医学杂志,2018,24(2):263-271.
[8] 叶圣荣,施琳琦,李丹,等.汉黄芩苷对肾缺血/再灌注损伤大鼠肾功能及NF-κB/iNOS/NO通路的影响[J].中国中医急症,2018,27(6):959-966.
[9] WU D,LIU J,CHEN J,et al.miR-449a suppresses tumor growth,migration,and invasion in non-small cell lung cancer by targeting a HMGB1-Mediated NF-κB signaling pathway[J].Oncol Res,2019,27(2):227-235.
[10] FEIBO X,QIANG J,JIAN Z,et al.AlCl 3,inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production through suppressing NF-κB signaling pathway in murine peritoneal macrophages[J].Chemosphere,2018,456(18):463-472.
[11] XUE L P,LU B,GAO B B,et al.NLRP3 promotes glioma cell proliferation and invasion via the interleukin-1β/NF-κB p65 signals[J].Oncol Res,2019,27(5):557-564.
[12] 赵锦,朱雯.淫羊藿苷对IgA肾病大鼠纤维化和炎症反应的调控作用[J].免疫学杂志,2018,34(5):385-392.
[13] ZHANG L,WANG X Z,LI Y S,et al.Icariin ameliorates IgA nephropathy by inhibition of nuclear factor kappa b/Nlrp3 pathway[J].Febs Open Bio,2017(1):54-63.
[14] TSAI Y L,HUA K F,CHEN A,et al.NLRP3 inflammasome:pathogenic role and potential therapeutic target for IgA nephropathy[J].Sci Rep,2017,24(7):41123-41127.
[15] 朱水兰,吴青华,涂珺.汉黄芩苷调控NLRP3/SOCS3-TLR4-NF-κB炎症通路改善肝细胞胰岛素抵抗的研究[J].中国中药杂志,2019,44(20):4504-4510.
[16] 叶圣荣,施琳琦,李丹,等.汉黄芩苷对肾缺血/再灌注损伤大鼠肾功能及NF-κB/iNOS/NO通路的影响[J].中国中医急症,2018,27(6):959-966.

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