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针刺通过抑制铁死亡和上皮-间质转化改善糖尿病肾病大鼠的蛋白尿。

Acupuncture improve proteinuria in diabetic kidney disease rats by inhibiting ferroptosis and epithelial-mesenchymal transition.

作者信息

Yue J I, Xin-Yuan Z H A N G, Yun-Ming X I A O, Zi-Hao Z H U A N G, Xiao-Hui Y A N G, Xin-Ju L I

机构信息

College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, PR China.

Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, Institute of Nephrology & Beijing Key Laboratory, Beijing, 100700, PR China.

出版信息

Heliyon. 2024 Jul 2;10(13):e33675. doi: 10.1016/j.heliyon.2024.e33675. eCollection 2024 Jul 15.

DOI:10.1016/j.heliyon.2024.e33675
PMID:39071725
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11283055/
Abstract

OBJECTIVE

To explore the mechanism of acupuncture to relieve diabetic proteinuria in Diabetic Kidney Disease (DKD).

METHODS

A total of 10 male Sprague-Dawley rats were randomly selected as the negative control group (NC), and a further 30 rats were fed a high-fat diet (HFD) and intraperitoneal streptozotocin (STZ). The DKD model rats in the model group (DKD) and the acupuncture group (DKD + Acu) were randomly assigned. After 4 weeks of intervention, collected urine, peripheral blood, and renal tissues from all rats, and assessed blood urea nitrogen, serum creatinine, triglyceride, 24-h urine protein quantification, and blood glucose, left kidney weight, kidney body ratio index, then observe changes in renal histology in the rats. The renal cortex tissues of three rats from each group were sent for transcriptomic analysis. According to the results of transcriptomic analysis, various kits were used to detect SOD, MDA, GSH, GSH-px, and iron concentration. The expression levels of GPX4 and System Xc-, members of the antioxidative stress pathway, and TfR 1, SLC39A14, FTH 1, and SLC40A1, involved in iron metabolism, in the kidney tissues were measured by western blotting and reverse transcription-quantitative PCR. The expression of mesenchymal phenotype markers and podocyte-specific markers were evaluated by immunofluorescence.

RESULTS

Acupuncture promoted the levels of GSH, GSH-px, and SOD, decreased the level of MDA (P < 0.05), promoted the expression of GPX4 and System Xc- ( < 0.05), decreased the expression of TfR1 and SLC39A14 ( < 0.01), and increased the expression of FTH 1 and SLC40A1 ( < 0.05), inhibited the expression of TGF-β1, desmin, FSP-1, and α-SMA ( < 0.05), promoted the expression of Nephrin, Podocin, and CD2AP (P < 0.05).

CONCLUSION

Improving the ability of podocytes to prevent oxidative stress and restoring iron ion homeostasis, can improve Ferroptosis and block epithelial-mesenchymal transition, improve podocyte injury, restore filtration function, and reduce proteinuria in DKD rats.

摘要

目的

探讨针刺缓解糖尿病肾病(DKD)中糖尿病蛋白尿的机制。

方法

随机选取10只雄性Sprague-Dawley大鼠作为阴性对照组(NC),另外30只大鼠给予高脂饮食(HFD)并腹腔注射链脲佐菌素(STZ)。将模型组(DKD)和针刺组(DKD + Acu)的DKD模型大鼠随机分配。干预4周后,收集所有大鼠的尿液、外周血和肾组织,评估血尿素氮、血清肌酐、甘油三酯、24小时尿蛋白定量和血糖、左肾重量、肾体比指数,然后观察大鼠肾脏组织学变化。每组取3只大鼠的肾皮质组织进行转录组分析。根据转录组分析结果,使用各种试剂盒检测超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-px)和铁浓度。通过蛋白质免疫印迹法和逆转录-定量聚合酶链反应检测肾脏组织中抗氧化应激途径成员GPX4和System Xc-以及参与铁代谢的转铁蛋白受体1(TfR 1)、溶质载体家族39成员14(SLC39A14)、铁蛋白重链1(FTH 1)和溶质载体家族40成员1(SLC40A1)的表达水平。通过免疫荧光评估间充质表型标志物和足细胞特异性标志物的表达。

结果

针刺可提高GSH、GSH-px和SOD水平,降低MDA水平(P < 0.05),促进GPX4和System Xc-的表达(P < 0.05),降低TfR1和SLC39A14的表达(P < 0.01),增加FTH 1和SLC40A1的表达(P < 0.05),抑制转化生长因子-β1(TGF-β1)、结蛋白、成纤维细胞特异性蛋白1(FSP-1)和α-平滑肌肌动蛋白(α-SMA)的表达(P < 0.05),促进Nephrin、Podocin和CD2相关蛋白(CD2AP)的表达(P < 0.05)。

结论

提高足细胞预防氧化应激的能力并恢复铁离子稳态,可改善铁死亡并阻断上皮-间充质转化,改善足细胞损伤,恢复滤过功能,降低DKD大鼠蛋白尿水平。

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