ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Translational Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1616542
Ultrasound combined with microbubble enhanced renoprotective effects of NLRP3 inflammasome inhibitor MCC950 in CKD model
Provisionally accepted
- 1Department of Ultrasound, First Affiliated Hospital of Chengdu Medical College, Chengdu, China
- 2Nanbu Country People’s Hospital, Nanchong, Sichuan Province, China
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Objective: This study evaluated the effectiveness of the NLRP3 inflammasome inhibitor MCC950 combined with ultrasound (US) and microbubbles (MBs) on kidney function and fibrosis in a rat model of chronic kidney disease (CKD).Methods: After establishing the model, SD rats were divided into eight groups (n=5): Control, CKD, MCC950 (10 mg/kg), MCC950 (5 mg/kg), US+MCC950 (5 mg/kg), US+MBs+MCC950 (5 mg/kg), US and US+MBs. MCC950 was administered at high (10mg/kg) or low (5mg/kg) doses, and 200 μL of sulfur hexafluoride microbubbles was delivered via tail vein injection. Ultrasound (mechanical index 0.99) was applied over the kidneys for 10 minutes every two days for six sessions post-injection. Renal function was assessed from urine and blood samples. Kidney tissues were examined using HE and Masson staining, while mRNA and protein levels of NLRP3, caspase-1, ASC, IL-1β, and IL-18 were quantified via RT-qPCR, immunohistochemistry, and ELISA.Results: Treatment with MCC950 (10 mg/kg), US + MCC950 (5 mg/kg), and US + MBs + MCC950 (5 mg/kg) significantly reduced serum creatinine, blood urea nitrogen, and albumin-to-creatinine ratios, and alleviated kidney damage and fibrosis compared to untreated CKD rats. Notably, US + MBs + MCC950 (5 mg/kg) was as effective as 10 mg/kg MCC950 treatment, with US + MBs further enhancing MCC950's inhibitory effects on NLRP3 inflammasome activity in renal tissues, manifesting as reductions in the mRNA and protein expression of NLRP3, caspase-1, ASC, IL-1β and IL-18.The combination of US and MB therapy with MCC950 improves renal function and reduces fibrosis in CKD rats, providing promising evidence for its potential in renal protection and the treatment of inflammatory disorders.
Keywords: ultrasound, Microbubble, CKD, renal fibrosis, NLRP3, MCC950
Received: 23 Apr 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Wen, Tu, Ren, Liu, Jiang, Wu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bin Tu, Department of Ultrasound, First Affiliated Hospital of Chengdu Medical College, Chengdu, China
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