Tetrandrine improves oxidative stress and pyroptosis of podocytes in diabetic kidney disease by regulating TXNIP/NLRP3/GSDMD signaling pathway

IF 2.2 4区 生物学 Q3 CELL BIOLOGY
Lujun Tang, Liumei Yuan, Di Ren, Jiebin Huang, Renjie Liu, Zhiwei Xia, Na Huang, Shangbo Zhang
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引用次数: 0

Abstract

Podocyte injury from oxidative stress and pyroptosis is closely linked with diabetic kidney disease (DKD). Here, Tetrandrine (TET), derived from tetrandrine root, with anti-inflammatory and antioxidant traits, was studied for its role in podocyte oxidative stress and pyroptosis in DKD. A rat model of DKD was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin (STZ). Renal function was assessed using urinary albumin to creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN) levels. Renal pathological morphology was evaluated by hematoxylin-eosin (HE) staining and Masson staining. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were detected with commercially available kits. DCFH-DA probe was used to detect intracellular ROS levels. Western blot detected pyroptosis-related proteins (TXNIP, NLRP3, GSDMD-N, pro-caspase-1). Inflammatory factors (IL-1β and IL-18) levels were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence staining observed the expression and localization of GSDMD. Administration of TET alleviated renal damage in rats with DKD. In DKD rats, TET suppressed the TXNIP/NLRP3/GSDMD pathway, leading to a decrease in oxidative stress and pyroptosis within the renal tissue. In vitro, by inhibiting the TXNIP/NLRP3/GSDMD signaling pathway, TET mitigated podocyte oxidative stress and pyroptosis triggered by high glucose. Following TXNIP overexpressing, podocyte oxidative stress and pyroptosis that TET initially suppressed were subsequently reversed. Our results reveal that TET represses podocyte oxidative stress and pyroptosis through TXNIP/NLRP3/GSDMD pathway, which provides new therapeutic targets for DKD treatment.

Abstract Image

粉防己碱通过调节TXNIP/NLRP3/GSDMD信号通路改善糖尿病肾病足细胞氧化应激和焦亡。
氧化应激和焦亡引起的足细胞损伤与糖尿病肾病(DKD)密切相关。本研究从粉防己碱根中提取具有抗炎和抗氧化特性的粉防己碱(TET),研究其在DKD足细胞氧化应激和焦亡中的作用。采用高脂饲粮联合腹腔注射链脲佐菌素(STZ)建立大鼠DKD模型。采用尿白蛋白与肌酐比值(UACR)、血清肌酐(Scr)和血尿素氮(BUN)水平评估肾功能。采用苏木精-伊红(HE)染色和马松染色评价肾脏病理形态。用市售试剂盒检测丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)。DCFH-DA探针检测细胞内ROS水平。Western blot检测焦热相关蛋白(TXNIP, NLRP3, GSDMD-N, pro-caspase-1)。采用酶联免疫吸附试验(ELISA)检测炎症因子(IL-1β和IL-18)水平。免疫荧光染色观察GSDMD的表达和定位。TET可减轻DKD大鼠肾损害。在DKD大鼠中,TET抑制TXNIP/NLRP3/GSDMD通路,导致肾组织氧化应激和焦亡减少。在体外,TET通过抑制TXNIP/NLRP3/GSDMD信号通路,减轻高糖引起的足细胞氧化应激和焦亡。TXNIP过表达后,TET最初抑制的足细胞氧化应激和焦亡随后逆转。我们的研究结果表明TET通过TXNIP/NLRP3/GSDMD通路抑制足细胞氧化应激和焦亡,为DKD治疗提供了新的靶点。
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来源期刊
Journal of Molecular Histology
Journal of Molecular Histology 生物-细胞生物学
CiteScore
5.90
自引率
0.00%
发文量
68
审稿时长
1 months
期刊介绍: The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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