[1]魏晓菲,王晨丹.雷公藤甲素调控NLRP3/GSDMD/IL-1β途径改善六价铬对足细胞损伤的机制研究[J].陕西中医,2024,(9):1172-1175,1185.[doi:DOI:10.3969/j.issn.1000-7369.2024.09.004]
　WEI Xiaofei,WANG Chendan.Study on the mechanism of triptolide regulating NLRP3/GSDMD/IL-1β pathway to improve podocyte injury induced by Cr(Ⅵ)[J].,2024,(9):1172-1175,1185.[doi:DOI:10.3969/j.issn.1000-7369.2024.09.004]
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雷公藤甲素调控NLRP3/GSDMD/IL-1β途径改善六价铬对足细胞损伤的机制研究
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2024年9期
页码:
1172-1175,1185
栏目:
基础研究
出版日期:
2024-09-05

文章信息/Info

Title:
Study on the mechanism of triptolide regulating NLRP3/GSDMD/IL-1β pathway to improve podocyte injury induced by Cr(Ⅵ)
作者:
魏晓菲1; 王晨丹1; 2
(1.山西中医药大学第三临床学院,山西 太原 030024; 2.山西省人民医院肾内科,山西 太原 030002)
Author(s):
WEI Xiaofei; WANG Chendan
(The Third Clinical College of Shanxi University of Traditional Chinese Medicine,Taiyuan 030024,China)
关键词:
雷公藤甲素;  六价铬;  足细胞;  NLRP3炎症小体;  慢性肾脏病;  细胞焦亡
Keywords:
Triptolide;  Cr(Ⅵ);  Podocyte;  NLRP3;  Chronic kidney disease;  Pyroptosis
分类号:
R 692
DOI:
DOI:10.3969/j.issn.1000-7369.2024.09.004
文献标志码:
A
摘要:
目的:通过构建小鼠足细胞损伤模型,探讨雷公藤甲素(TP)通过调控NLRP3/GSDMD/IL-1β通路对足细胞的保护作用。方法:培养小鼠足细胞MPC5,通过构建Cr(Ⅵ)足细胞损伤模型,分为正常组(Control组)、Cr(Ⅵ)组、Cr(Ⅵ)+TP组(TP组)。通过CCK-8法分别检测30～150 μmol/L Cr(Ⅵ)作用于足细胞后对足细胞生存活力的影响和2～10 ng/ml TP作用于Cr(Ⅵ)染毒后的足细胞,以确定Cr(Ⅵ)和TP干预的最佳浓度和时间,Western blot法检测NLRP3、Caspase-1、GSDMD、IL-1β和IL-18焦亡相关蛋白的表达情况,细胞免疫荧光法检测足细胞WT-1蛋白表达情况。结果:CCK法结果表示,选取Cr(Ⅵ)浓度为150 μmol/L,1 h干预细胞,TP浓度为2 ng/ml,24 h干预细胞。Western blot结果表明发现,与Control组相比,Cr(Ⅵ)组中NLRP3、Caspase-1、GSDMD、IL-1β和IL-18表达升高(P<0.05,P<0.01),TP组中NLRP3、Caspase-1、GSDMD、IL-1β和IL-18表达降低(P<0.05)。细胞免疫荧光结果显示,与Control组相比,Cr(Ⅵ)组中WT-1的阳性表达显著降低,经TP干预后表达升高。结论:TP能够改善Cr(Ⅵ)对足细胞的损伤作用并通过抑制NLRP3/GSDMD/IL-1β信号通路来实现的。
Abstract:
Objective:To explore the protective effect of triptolide(TP)on podocytes by regulating NLRP3/GSDMD/IL-1β pathway by establishing a mouse podocyte injury model.Methods:Mouse podocyte MPC5 was cultured and Cr(Ⅵ)podocyte injury model was established.The mice were divided into normal group(Control group),Cr(Ⅵ)group and Cr(Ⅵ)+TP group(TP group).The effect of 30～150 μmol/L Cr(Ⅵ)on podocyte viability and the effect of 2～10 ng/ml TP on podocyte treated by Cr(Ⅵ)were detected by CCK-8 method to determine the best concentration and time of Cr(Ⅵ)and TP intervention.The expression of NLRP3,Caspase-1,GSDMD,IL-1β and IL-18 scorch related protein was detected by Western blot method,and the expression of WT-1 protein was detected by cellular immunofluorescence.Results:The results of CCK assay showed that the cells were treated with Cr(Ⅵ)at 150 μmol/L for 1 h and TP at 2 ng/ml for 24 h.The results of Western blot showed that the expression of NLRP3,Caspase-1,GSDMD,IL-1β and IL-18 in Cr(Ⅵ)group was higher than that in Control group(P<0.05,P<0.01).The expression of NLRP3,Caspase-1,GSDMD,IL-1β,and IL-18 was decreased in the TP group(P<0.05).The results of cellular immunofluorescence showed that the positive expression of WT-1 in Cr(Ⅵ)group was significantly lower than that in Control group.The expression was elevated after the TP intervention.Conclusion:TP can improve the injury effect of Cr(Ⅵ)on podocytes by inhibiting NLRP3/GSDMD/IL-1β signal pathway.

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备注/Memo

备注/Memo:
基金项目:山西省科技厅自然科学研究面上项目(202103021224382); 中国医师协会循证医学专业委员会肾科学组“PRO·润”基金资助项目(KYS2021-03-02-10)
更新日期/Last Update: 2024-09-09