Pharmacological inhibition of the NLRP3 inflammasome attenuates kidney apoptosis, fibrosis, and injury in Dahl salt-sensitive rats.

IF 2.2 4区医学 Q2 UROLOGY & NEPHROLOGY

Clinical and Experimental Nephrology Pub Date : 2024-11-22 DOI:10.1007/s10157-024-02567-7

Yue Wang, Yuhang Wu, Jiayu Ren, Ying Wang, Imran Perwaiz, Hongtong Su, Jing Li, Peng Qu

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引用次数: 0

Abstract

Background: Salt-sensitive hypertension (SSH) is the most severe form of hypertension, and the presence of NLRP3 inflammasome plays a crucial role in its pathogenesis. Although MCC950 has shown therapeutic potential for hypertension and kidney injury, its mechanism of action remains unclear.

Methods: Dahl salt-sensitive (SS) rats and their salt-tolerant aptamer control SS-13^BN (BN) rats were randomly assigned to four groups: SS rats intraperitoneally administered physiological saline (SS + vehicle) or MCC950 (SS + MCC950), and BN rats intraperitoneally administered physiological saline (BN + vehicle) or MCC950 (BN + MCC950). All rats were given 2% saline for drinking and received intraperitoneal injections of physiological saline or MCC950 (5 mg/kg) every other day. Biomarkers such as serum creatinine, urinary protein, sodium retention, NLRP3 inflammasome, inflammation, apoptosis, fibrosis, sodium channels and histopathological changes in kidney injury were evaluated in blood, urine, and kidney tissues.

Results: Compared with the SS + vehicle group, the SS + MCC950 group showed significantly lower blood pressure levels. Additionally, inhibition of NLRP3 inflammasome activation was observed along with reduced inflammation, apoptosis, fibrosis, and sodium retention in the kidneys.

Conclusions: The findings suggest that pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure in SS rats and alleviates related kidney injury by suppressing inflammation, apoptosis, fibrosis, and sodium retention.

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药物抑制 NLRP3 炎性体可减轻达尔盐敏感大鼠肾脏的凋亡、纤维化和损伤。

背景：盐敏感性高血压（SSH）是高血压的最严重形式，NLRP3炎性体的存在在其发病机制中起着至关重要的作用。虽然 MCC950 对高血压和肾损伤具有治疗潜力，但其作用机制仍不清楚：方法：将达氏盐敏感（SS）大鼠及其耐盐合剂对照 SS-13BN （BN）大鼠随机分为四组：SS 大鼠腹腔注射生理盐水（SS + 车辆）或 MCC950（SS + MCC950），BN 大鼠腹腔注射生理盐水（BN + 车辆）或 MCC950（BN + MCC950）。所有大鼠均饮用 2% 生理盐水，每隔一天腹腔注射生理盐水或 MCC950（5 mg/kg）。对血液、尿液和肾组织中的血肌酐、尿蛋白、钠潴留、NLRP3炎症小体、炎症、细胞凋亡、纤维化、钠通道等生物标志物以及肾损伤的组织病理学变化进行评估：结果：与 SS + 车辆组相比，SS + MCC950 组的血压水平明显降低。此外，在抑制 NLRP3 炎性体活化的同时，肾脏中的炎症、细胞凋亡、纤维化和钠潴留也有所减轻：研究结果表明，药物抑制 NLRP3 炎性体可降低 SS 大鼠的血压，并通过抑制炎症、细胞凋亡、纤维化和钠潴留减轻相关的肾损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Experimental Nephrology UROLOGY & NEPHROLOGY-

CiteScore

4.10

自引率

4.30%

发文量

135

审稿时长

4-8 weeks

期刊介绍： Clinical and Experimental Nephrology is a peer-reviewed monthly journal, officially published by the Japanese Society of Nephrology (JSN) to provide an international forum for the discussion of research and issues relating to the study of nephrology. Out of respect for the founders of the JSN, the title of this journal uses the term “nephrology,” a word created and brought into use with the establishment of the JSN (Japanese Journal of Nephrology, Vol. 2, No. 1, 1960). The journal publishes articles on all aspects of nephrology, including basic, experimental, and clinical research, so as to share the latest research findings and ideas not only with members of the JSN, but with all researchers who wish to contribute to a better understanding of recent advances in nephrology. The journal is unique in that it introduces to an international readership original reports from Japan and also the clinical standards discussed and agreed by JSN.