Department of Emergency Critical Care Medicine, The Fourth People's Hospital of Jinan, Jinan, Shandong, China (mainland).
Med Sci Monit. 2020 Jul 16;26:e923900. doi: 10.12659/MSM.923900.
BACKGROUND Acute kidney injury (AKI) caused by sepsis is a very dangerous clinical complication. This study explored the effects of calcitonin gene-related peptides (CGRP) on AKI and its mechanisms. MATERIAL AND METHODS We cultured renal proximal tubular epithelial cells (HK-2 cells) and induced AKI models using LPS. Recombinant human CGRP was used to stimulate HK-2 cells and we detected markers of kidney injury (KIM-1 and NGAL) to determine the protective effect of CGRP on HK-2 cells. In addition, we constructed Sirt1-overexpressing lentivirus and small interfering RNA to increase or decrease Sirt1 expression in HK-2 cells to verify that CGRP protects HK-2 cells by regulating Sirt1. RESULTS After CGRP stimulation of HK-2 cells, LPS-induced HK-2 cell damage was significantly ameliorated, showing a decrease in the expression of KIM-1, NGAL, and inflammatory factors. In addition, Sirt1 was significantly increased in CGRP-stimulated HK-2 cells. After transfection of HK-2 cells with Lenti-Sirt1, inflammation and damage of HK-2 cells were both reduced, indicating that Sirt1 has a protective effect on HK-2 cells and can mediate the protective effect of CGRP on HK-2 cells. Therefore, the protective effect of CGRP on HK-2 cells was also attenuated after reducing Sirt1 in HK-2 cells. Finally, we used CGRP to treat LPS-induced mice and verified the protective effect of CGRP on mouse AKI. CONCLUSIONS CGRP has a significant anti-inflammatory effect. In the treatment of AKI, CGRP can increase the expression of Sirt1 to exert an anti-inflammatory effect and has a good protective effect on LPS-induced HK-2 cells.
脓毒症引起的急性肾损伤（AKI）是一种非常危险的临床并发症。本研究探讨降钙素基因相关肽（CGRP）对 AKI 的作用及其机制。
我们培养了肾近端管状上皮细胞（HK-2 细胞），并用 LPS 诱导 AKI 模型。用重组人 CGRP 刺激 HK-2 细胞，检测肾损伤标志物（KIM-1 和 NGAL），以确定 CGRP 对 HK-2 细胞的保护作用。此外，我们构建了 Sirt1 过表达慢病毒和小干扰 RNA，以增加或减少 HK-2 细胞中的 Sirt1 表达，验证 CGRP 是否通过调节 Sirt1 来保护 HK-2 细胞。
在 CGRP 刺激 HK-2 细胞后，LPS 诱导的 HK-2 细胞损伤明显改善，KIM-1、NGAL 和炎症因子的表达降低。此外，CGRP 刺激的 HK-2 细胞中 Sirt1 明显增加。转染 HK-2 细胞 Lenti-Sirt1 后，HK-2 细胞的炎症和损伤均减轻，表明 Sirt1 对 HK-2 细胞具有保护作用，并能介导 CGRP 对 HK-2 细胞的保护作用。因此，降低 HK-2 细胞中的 Sirt1 后，CGRP 对 HK-2 细胞的保护作用也减弱。最后，我们用 CGRP 治疗 LPS 诱导的小鼠，验证了 CGRP 对小鼠 AKI 的保护作用。
CGRP 具有显著的抗炎作用。在 AKI 的治疗中，CGRP 可以增加 Sirt1 的表达，发挥抗炎作用，对 LPS 诱导的 HK-2 细胞具有良好的保护作用。
