Department of Nephrology, The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan, Changsha, PR China.
Pharmacology. 2017;100(5-6):253-260. doi: 10.1159/000479525. Epub 2017 Aug 11.
BACKGROUND/AIM: Focal segmental glomerulosclerosis (FSGS) typically presents with nephrotic range proteinuria, which could eventually develop into end-stage renal disease. Resveratrol (RSV) is a natural polyphenol compound, which has been reported to suppress inflammatory response and renal interstitial fibrosis. This study is aimed at evaluating the renoprotective effect of RSV treatment on adriamycin-induced FSGS.
In Balb/c mice, adriamycin nephropathy was induced by adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then the mice were treated with RSV (40 mg/kg body weight) once daily by oral gavage, again starting on the day of adriamycin injection and continued for 6 weeks. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis.
When treated with adriamycin, the expressions of C3aR, C5aR, sphingosine kinase 1 (Sphk1), and soluble urokinase-type plasminogen activator receptor (suPAR) were upregulated, while RSV treatment could inhibit the expressions of C3aR, C5aR, Sphk1, and suPAR, eventually leading to anti-inflammatory and anti-fibrosis conditions.
RSV attenuates adriamycin-induced FSGS through C3aR/C5aR-Sphk1 pathway.
背景/目的：局灶节段性肾小球硬化症（FSGS）通常表现为肾病范围蛋白尿，最终可能发展为终末期肾病。白藜芦醇（RSV）是一种天然多酚化合物，据报道可抑制炎症反应和肾间质纤维化。本研究旨在评估 RSV 治疗对阿霉素诱导的 FSGS 的肾脏保护作用。
在 Balb/c 小鼠中，通过尾静脉在第 0 天用阿霉素（10mg/kg 体重，溶于生理盐水）诱导阿霉素肾病。然后，用 RSV（40mg/kg 体重）通过口服灌胃每天一次进行治疗，从阿霉素注射的那一天开始，持续 6 周。6 周后，处死小鼠；收集肾脏和血液样本进行进一步分析。
用阿霉素处理时，C3aR、C5aR、鞘氨醇激酶 1（Sphk1）和可溶性尿激酶型纤溶酶原激活物受体（suPAR）的表达上调，而 RSV 治疗可抑制 C3aR、C5aR、Sphk1 和 suPAR 的表达，最终导致抗炎和抗纤维化状态。
RSV 通过 C3aR/C5aR-Sphk1 途径减轻阿霉素诱导的 FSGS。
