Advances in Research on Pathological and Molecular Mechanism of Hyperuricemic Nephropathy Based on Animal Models
10.12300/j.issn.1674-5817.2023.123
- VernacularTitle:基于动物模型的高尿酸肾病病理及分子机制研究进展
- Author:
Fangqi BAO
1
;
Haiye TU
2
;
Mingsun FANG
3
;
Qian ZHANG
3
;
Minli CHEN
3
Author Information
1. Huashan Hospital, Fudan University, Shanghai 200032, China
2. College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China
3. Academy of Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
- Publication Type:Journal Article
- Keywords:
Hyperuricemia;
Hyperuricemic nephropathy;
Pathological mechanism;
Animal model
- From:
Laboratory Animal and Comparative Medicine
2024;44(2):180-191
- CountryChina
- Language:Chinese
-
Abstract:
Uric acid (UA), the final product of human purine metabolism, can cause hyperuricemia (HUA) when excessively accumulated. HUA is closely linked to chronic kidney diseases (CKD) and is considered an independent risk factor. Hyperuricemic nephropathy, a form of CKD induced by HUA, has seen significant advances in understanding through research into the pathogenic roles of uric acid and the development of HUA animal models. Although progress has been made in understanding the pathophysiological mechanisms by which UA induces CKD, much remains to be learned about its pathological molecular mechanisms. New approaches in animal modeling or the selection of model animals may potentially lead to significant breakthroughs in research on hyperuricemia as well as related CKD. This paper reviews the research progress on the molecular mechanisms of hyperuricemic nephropathy, focusing on oxidative stress, inflammation, autophagy, fibrosis, and gut microbiota. Oxidative stress is induced by uric acid intracellularly through xanthine oxidase, NADPH oxidases, and mitochondria, leading to cellular damage. In terms of inflammation, uric acid crystals can activate the NLRP3 inflammasome, triggering an inflammatory cascade. The role of free uric acid as a pro-inflammatory agent, however, remains controversial. Depending on the study conducted, autophagy has been found to either alleviate or exacerbate inflammation induced by uric acid. Fibrosis, particularly through epithelial-mesenchymal transition (EMT), is a major mechanism by which uric acid causes glomerulosclerosis and tubulointerstitial fibrosis. Extensive research has explored various signaling pathways involved in uric acid-induced EMT. Beneficial gut microbiota protect the kidneys by synthesizing short-chain fatty acids, reducing urea’s enterohepatic circulation, and decreasing uric acid production. This paper aims to enhance understanding of the complex relationships between HUA and CKD, serving as a reference for further research and new drug development.
