Scutellarin Ameliorates Renal Injury via Increasing CCN1 Expression and Suppressing NLRP3 Inflammasome Activation in Hyperuricemic Mice.
Scutellarin Ameliorates Renal Injury via Increasing CCN1 Expression and Suppressing NLRP3 Inflammasome Activation in Hyperuricemic Mice.
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灯盏乙素通过增加CCN 1表达和抑制NLRP 3炎性体激活改善高尿酸血症小鼠的肾损伤
DOI：
10.3389/fphar.2020.584942
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发表时间：
2020
影响因子：
5.6
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Li G;Guan C;Xu L;Wang L;Yang C;Zhao L;Zhou B;Luo C;Luan H;Jiang W;Li C;Xu Y
大量证据表明，尿酸（UA）升高与高尿酸血症性肾病（HN）的肾小管损伤有关。灯盏乙素（Scutellarin）是从中药灯盏花（Erigeron breviscapus Hand-Mazz）中提取的一种具有生物活性的黄酮类化合物，广泛应用于心脑血管疾病的治疗。在本研究中，我们分析了灯盏乙素对HN的影响，通过使用C57 BL/6小鼠和人肾小管上皮细胞系HK-2，这是受到腺嘌呤/氧酮酸钾和UA模拟HN损伤。HN小鼠肾功能明显下降，SCr和血尿素氮（BUN）升高（p < 0.05）。苏木精-伊红染色结果显示HN小鼠肾组织有组织学损伤，肾小管损伤严重。灯盏乙素可剂量依赖性地减轻HN模型的肾损伤（p < 0.05），20 mg/kg/d剂量显著降低Scr水平血尿素氮（BUN）（151.12 ± 30.24 mmol/L vs. 210.43 ± 45.67 mmol/L，p < 0.05）。类似地，灯盏乙素降低HN小鼠中NGAL、Kim-1、半胱氨酸蛋白酶抑制剂C和IL-18蛋白表达水平（p < 0.05）。与对照HK-2相比，过表达的CCN 1不能诱导NLRP 3炎性小体活化，NLRP 3、ASC和pro-caspase-1的mRNA和蛋白表达水平没有变化。然而，HK-2显示出显著的NLRP 3炎性体活化和凋亡。重要的是，CCN 1的敲除不仅加重了NLRP 3炎性体的激活和凋亡，而且消除了灯盏乙素在UA诱导的HK-2损伤中的保护作用。因此，灯盏乙素可能通过参与CCN 1对NLRP 3炎性体激活的调节机制来缓解HN进展。
Considerable evidences have indicated that elevated uric acid (UA) was involved in renal tubular injury leading to hyperuricemic nephropathy (HN). Scutellarin is a biologically active flavonoid derived from the Chinese traditional herb Erigeron breviscapus Hand-Mazz, which has been widely used in the treatment of cardiovascular and cerebrovascular diseases. In the present study, we analyzed the effect of scutellarin on HN, by using C57BL/6 mice and human renal tubular epithelial cell line HK-2 which was subjected to adenine/potassium oxonate and UA to mimic a HN injury. The HN mice showed a significant decrease in renal function with the increased SCr and blood urea nitrogen (BUN) (p < 0.05). Hematoxylin–eosin staining results showed a histological injury in HN mice kidney tissues with severe tubular damage. Scutellarin dose dependently alleviated the renal injury of the HN model (p < 0.05), and a dose of 20 mg/kg/day remarkably reduced the Scr level (26.10 ± 3.23 μmol/ml vs. 48.39 ± 7.51 μmol/ml, p < 0.05) and BUN (151.12 ± 30.24 mmol/L vs. 210.43 ± 45.67 mmol/L, p < 0.05) compared with the HN model group. Similarly, scutellarin decreased NGAL, Kim-1, cystatin C, and IL-18 protein expression levels in HN mouse (p < 0.05). Overexpressed CCN1 could not induce NLRP3 inflammasome activation, with no change of mRNA and protein expression levels of NLRP3, ASC, and pro-caspase-1 compared with the control HK-2. However, HK-2 showed a significant NLRP3 inflammasome activation and apoptosis. Importantly, knockdown of CCN1 not only aggravated NLRP3 inflammasome activation and apoptosis but also abrogated the protective effect of scutellarin in UA-induced HK-2 injury. Thus, scutellarin might alleviate HN progression via a mechanism involved in CCN1 regulation on NLRP3 inflammasome activation.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.6
作者：
Braga TT;Forni MF;Correa-Costa M;Ramos RN;Barbuto JA;Branco P;Castoldi A;Hiyane MI;Davanso MR;Latz E;Franklin BS;Kowaltowski AJ;Camara NO
通讯作者：
Camara NO
影响因子：
3.9
作者：
Sun C;Li C;Li X;Zhu Y;Su Z;Wang X;He Q;Zheng G;Feng B
通讯作者：
Feng B
影响因子：
7.5
作者：
Nakhate, Kartik T.;Bharne, Ashish P.;Kokare, Dadasaheb M.
通讯作者：
Kokare, Dadasaheb M.
别嘌呤醇、芦丁和槲皮素减轻果糖摄入引起的大鼠高尿酸血症和肾功能障碍：肾脏有机离子转运蛋白参与
DOI：
10.1152/ajprenal.90767.2008
发表时间：
2009-10-01
影响因子：
4.2
作者：
Hu, Qing-Hua;Wang, Chuang;Kong, Ling-Dong
通讯作者：
Kong, Ling-Dong