Rhein attenuates obesity-related glomerulopathy by inhibiting the P۲X۷R/NLRP۳ inflammasome pathway and protecting podocytes
- سال انتشار: 1404
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 28، شماره: 12
- کد COI اختصاصی: JR_IJBMS-28-12_015
- زبان مقاله: انگلیسی
- تعداد مشاهده: 32
نویسندگان
Department of Nephrology, The Third People’s Hospital Affiliated to Fujian Univer-sity of Traditional Chinese Medicine, Fuzhou, Fujian, China
State Key Laboratory of Infectious Disease Vaccine Development, Xiang An Bio-medicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecu-lar Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China
State Key Laboratory of Infectious Disease Vaccine Development, Xiang An Bio-medicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecu-lar Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou ۳۱۰۰۰۳, Zhejiang, China
Department of Nephrology, The Third People’s Hospital Affiliated to Fujian Univer-sity of Traditional Chinese Medicine, Fuzhou, Fujian, China
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fuzhou, Fujian, China
Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
State Key Laboratory of Infectious Disease Vaccine Development, Xiang An Bio-medicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecu-lar Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China
The Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
چکیده
Objective(s): To investigate the renoprotective effects of Rhein in obesity-related glomerulopathy (ORG) by inhibiting the P۲X۷ receptor (P۲X۷R)/NOD-like receptor protein ۳ (NLRP۳) inflammasome pathway.Materials and Methods: ORG was induced in C۵۷BL/۶J mice with a high-fat diet (HFD) for ۱۰ weeks, fol-lowed by oral Rhein treatment (۷۰ or ۳۰۰ mg/kg/day) for ۱۰ weeks. Renal function, histology, and podocyte injury were assessed. In vitro, leptin-induced podocyte injury was treated with Rhein or P۲X۷R antagonists (KN-۶۲ or A-۴۳۸۰۷۹). P۲X۷R/NLRP۳ activation, inflammation, and oxidative stress were evaluated.Results: HFD-induced weight gain, dyslipidemia, renal dysfunction, glomerular hypertrophy, and podocyte injury. Rhein reduced serum triglycerides (TG) and total cholesterol (TC), lowered blood urea nitrogen (BUN), improved urinary protein excretion, and alleviated histological damage. Rhein inhibited P۲X۷R and NLRP۳ activation, down-regulated caspase-۱, interleukin (IL)-۱β, and IL-۱۸, and restored podocyte markers (Nephrin, Podocin). In vitro, Rhein mitigated leptin-induced podocyte injury and inflammasome activation.Conclusion: Rhein protects against ORG by suppressing the P۲X۷R/NLRP۳ pathway, reducing inflammation and oxidative stress, and preserving podocyte integrity, highlighting its therapeutic potential.کلیدواژه ها
Inflammation, Leptin, NLRP۳ inflammasome, Obesity-related- glomerulopathy, P۲X۷ receptor, Podocyte, Rheinاطلاعات بیشتر در مورد COI
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