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小孢葡萄穗霉三萜烯酚-7(一种具有抗炎和抗氧化活性的小分子)在急性肾损伤小鼠模型中的强效疗效。

Potent efficacy of Stachybotrys microspora triprenyl phenol-7, a small molecule having anti-inflammatory and antioxidant activities, in a mouse model of acute kidney injury.

作者信息

Shibata Keita, Hashimoto Terumasa, Hasumi Keiji, Nobe Koji

机构信息

Division of Pharmacology, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.

Division of Pharmacology, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.

出版信息

Eur J Pharmacol. 2021 Nov 5;910:174496. doi: 10.1016/j.ejphar.2021.174496. Epub 2021 Sep 7.

Abstract

Acute kidney injury (AKI) increases the risk of chronic kidney disease (CKD), complicates existing CKD, and can lead to the end-stage renal disease. However, there are no approved effective therapeutics for AKI. Recent studies have suggested that inflammation and oxidative stress are the primary causes of AKI. We previously reported the potential anti-inflammatory and antioxidant activities of Stachybotrys microspora triprenyl phenol-7 (SMTP-7). The aim of the present study was to evaluate the efficacy of SMTP-7 in AKI model mice. AKI was induced in mice by ischemia of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the removal of right kidney. The efficacy of SMTP-7 was determined by measuring the renal function using urine and serum samples and morphological assessment. For deciphering the mechanism of action of SMTP-7, inflammatory cytokines and oxidative stress in kidney were detected. SMTP-7 (0.01, 0.1, 1, 10 mg/kg) dose-dependently improved the renal function. In addition, it improved the damage to renal tubules and exhibited anti-inflammatory and antioxidant activities in the kidney of AKI mice. These results indicate the potential of SMTP-7 as a medicinal compound for the treatment of AKI.

摘要

急性肾损伤(AKI)会增加慢性肾脏病(CKD)的风险,使现有的CKD病情复杂化,并可能导致终末期肾病。然而,目前尚无获批的针对AKI的有效治疗方法。最近的研究表明,炎症和氧化应激是AKI的主要病因。我们之前报道了微小毛霉三萜烯酚-7(SMTP-7)具有潜在的抗炎和抗氧化活性。本研究的目的是评估SMTP-7在AKI模型小鼠中的疗效。通过在切除右肾2周后,将左肾动脉和静脉缺血45分钟后再灌注来诱导小鼠发生AKI。通过使用尿液和血清样本测量肾功能以及进行形态学评估来确定SMTP-7的疗效。为了解析SMTP-7的作用机制,检测了肾脏中的炎性细胞因子和氧化应激情况。SMTP-7(0.01、0.1、1、10毫克/千克)呈剂量依赖性地改善了肾功能。此外,它改善了肾小管损伤,并在AKI小鼠的肾脏中表现出抗炎和抗氧化活性。这些结果表明SMTP-7作为治疗AKI的药用化合物具有潜力。

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