Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Life Sci. 2020 Aug 15;255:117719. doi: 10.1016/j.lfs.2020.117719. Epub 2020 May 16.
To investigate the protective function of exosomes from adipose tissue-derived mesenchymal stem cells (AMSCs) in sepsis-induced acute kidney injury (AKI) in mice and the possible underlying mechanism in order to provide a theoretical and experimental basis for using exosomes in clinical.
The AKI model was prepared through cecal ligation and puncture (CLP). Exosomes were injected via the tail vein of mice. Male C57/BL6 mice (18-22 g; 6-8 weeks old) were randomly grouped. Firstly, after mice were modeled, the variations of inflammatory cytokines and kidney functions at different time points (0, 6, 12, 24 and 48 h) were comprehended. Secondly, mice were divided into Sham, CLP and CLP + Exo, and the survival rates of each group were observed. Lastly, a time point (24 h) was selected for exploring the effect and mechanism of exosomes. The levels of inflammatory cytokines in serum were detected by ELISA, while the kidney was by immunohistochemistry. Kidney histopathological score were analyzed by hematoxylin-eosin (HE) staining. The protein levels of sirtuin 1 (SIRT1), inflammation-related and apoptosis-related were detected by western blot.
In CLP group, renal function gradually deteriorated, and the kidneys was in a state of inflammation, apoptosis and microcirculation disorders. However, SIRT1 was activated after intervention of exosomes in CLP mice, which reversed above changes. The mortality was reduced with treatment of exosomes in AKI mice.
In mice of sepsis-induce AKI, the intervention of AMSCs derived exosomes played a renal protective effect. The mechanism may be through SIRT1 signaling pathway.
探讨脂肪组织间充质干细胞（AMSCs）来源的外泌体在脓毒症诱导的急性肾损伤（AKI）小鼠中的保护作用及其可能的作用机制，为外泌体在临床中的应用提供理论和实验依据。
采用盲肠结扎穿孔（CLP）法制备 AKI 模型，通过尾静脉注射小鼠外泌体。雄性 C57/BL6 小鼠（18-22g；6-8 周龄）随机分组。首先，在建模后，检测不同时间点（0、6、12、24 和 48h）炎症细胞因子和肾功能的变化。其次，将小鼠分为 Sham、CLP 和 CLP+Exo 组，观察各组的存活率。最后，选择一个时间点（24h）探索外泌体的作用和机制。采用 ELISA 法检测血清中炎症细胞因子水平，免疫组织化学法检测肾脏，苏木精-伊红（HE）染色法分析肾脏组织病理学评分。采用 Western blot 检测 SIRT1、炎症相关和凋亡相关蛋白的表达。
在 CLP 组中，肾功能逐渐恶化，肾脏处于炎症、凋亡和微循环障碍状态。然而，CLP 小鼠外泌体干预后 SIRT1 被激活，逆转了上述变化。AKI 小鼠外泌体治疗后死亡率降低。
在脓毒症诱导的 AKI 小鼠中，AMSCs 来源的外泌体发挥了肾脏保护作用。其机制可能通过 SIRT1 信号通路。
