Resveratrol Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis through C3aR/C5aR- Sphingosine Kinase 1 Pathway

Resveratrol Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis through C3aR/C5aR- Sphingosine Kinase 1 Pathway
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DOI:
10.1159/000479525
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发表时间:
2017-08
期刊:
影响因子:
3.1
通讯作者:
Guoyong Liu;Qiang Wang;Yan Shi;Xiaofei Peng;Hong Liu;Youming Peng;Liyu He
Guoyong Liu;Qiang Wang;Yan Shi;Xiaofei Peng;Hong Liu;Youming Peng;Liyu He
中科院分区:
医学4区
文献类型:
--
作者:
Guoyong Liu;Qiang Wang;Yan Shi;Xiaofei Peng;Hong Liu;Youming Peng;Liyu He

文献摘要

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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,据报道可以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。方法:第0天,Balb/c小鼠经尾静脉注射阿霉素(10 mg/kg体重,生理盐水稀释)诱发阿霉素肾病,然后用RSV(40 mg/kg体重)口服灌胃,每日1次,从注射阿霉素当天开始,持续6周。 6周时,处死小鼠;收集肾脏和血液样本进行进一步分析。结果:阿霉素治疗时,C3aR、C5aR、鞘氨醇激酶1(Sphk1)和可溶性尿激酶型纤溶酶原激活剂受体(suPAR)的表达上调,而RSV治疗可以抑制C3aR、C5aR、Sphk1和suPAR的表达,最终导致抗炎和抗纤维化。结论:RSV 通过 C3aR/C5aR-Sphk1 途径减弱阿霉素诱导的 FSGS。
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. Methods: 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. Results: 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. Conclusion: RSV attenuates adriamycin-induced FSGS through C3aR/C5aR-Sphk1 pathway.