Vitamin C alleviates hyperuricemia nephropathy by reducing inflammation and fibrosis
Vitamin C alleviates hyperuricemia nephropathy by reducing inflammation and fibrosis
复制标题
维生素 C 通过减少炎症和纤维化来缓解高尿酸血症肾病
DOI：
10.1111/1750-3841.15803
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发表时间：
2021-06-23
影响因子：
3.9
通讯作者：
Li, Haitao
中科院分区：
文献类型：
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作者：
Li, Hongling;Liu, Xuejiao;Li, Haitao
高尿酸血症会导致慢性肾脏疾病的发展。然而，历史上人们对它的研究兴趣有限。在这项研究中，我们通过使用氧酸钾诱导的高尿酸血症大鼠模型来模拟高尿酸血症肾病的发展。我们发现每天服用 10 毫克/公斤维生素 C 可以有效改善高尿酸血症肾病。与对照组相比，高尿酸血症大鼠的血清尿酸水平、黄嘌呤氧化酶活性和尿微量白蛋白水平分别显着升高5倍、1.5倍和4倍。与此同时，补充维生素 C 可使血清尿酸水平和黄嘌呤氧化酶活性恢复 20%，微量白蛋白水平恢复 50%。维生素 C 还可以缓解肾脏病理并降低促炎和促纤维化标志物的表达。进一步的机制研究表明，维生素 C 可能至少部分通过直接抑制 IL-6/JAK2/STAT3 信号通路来减轻尿酸单钠 (MSU) 晶体诱导的肾小管上皮细胞中的高尿酸血症肾病。同时，在巨噬细胞中，维生素C抑制TGF-β的表达，并使MSU诱导的ROS水平降低约35%。简而言之，我们的结果表明补充维生素 C 可延缓高尿酸血症肾病的进展。
Hyperuricemia contributes to chronic kidney disease development. However, it has been historically viewed with limited research interest. In this study, we mimicked the development of hyperuricemic nephropathy by using a potassium oxonate-induced hyperuricemia rat model. We found that administering vitamin C at 10 mg/kg/day effectively ameliorated hyperuricemic nephropathy. Compared to the control group, rats with hyperuricemia had significantly increased serum uric acid level, xanthine oxidase activity, and urine microalbumin level, by 5-fold, 1.5-fold, and 4-fold, respectively. At the same time, vitamin C supplementation reverted these values by 20% for serum uric acid level and xanthine oxidase activity and 50% for microalbumin level. Vitamin C also alleviated renal pathology and decreased the expression of pro-inflammatory and pro-fibrotic markers. A further mechanistic study suggested that vitamin C might attenuate hyperuricemic nephropathy in renal tubular epithelial cells induced by monosodium urate (MSU) crystal, at least in part, by directly inhibiting IL-6/JAK2/STAT3 signaling pathway. Meanwhile, in macrophages, vitamin C inhibited the expression of TGF-beta, and reduced ROS level induced by MSU by about 35%. In short, our results suggest that vitamin C supplementation delay the progression of hyperuricemic nephropathy.