Feng Li-Xin, Zhao Fei, Liu Qian, Peng Jin-Cheng, Duan Xiang-Jie, Yan Ping, Wu Xi, Wang Hong-Shen, Deng Yin-Hao, Duan Shao-Bin
Department of Nephrology, The Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan 410011, China.
Oxid Med Cell Longev. 2020 Jul 28;2020:6123459. doi: 10.1155/2020/6123459. eCollection 2020.
Acute kidney injury (AKI) is one of the common complications of sepsis. Heretofore, there is no effective treatment for septic AKI. Recent studies have revealed that besides treating hematological malignancies, human umbilical cord blood mononuclear cells (hUCBMNCs) show good therapeutic effects on other diseases. But whether hUCBMNCs can protect against septic AKI and its underlying mechanism are unknown.
The rat model of lipopolysaccharide- (LPS-) induced AKI was developed, and the injection of hUCBMNCs was executed to prevent and treat AKI. ML385, a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor, was used to silence Nrf2. The cell experiments were conducted to elaborate the protective mechanism of Nrf2 pathway.
An effective model of LPS-induced AKI was established. Compared to the rats only with LPS injection, the levels of inflammation, reactive oxygen species (ROS), and apoptosis in renal tissues after hUCBMNC injection were markedly attenuated. Pathological examination also indicated significant remission of renal tissue injury in the LPS+MNCs group, compared to rats in the LPS group. Transmission electron microscopy (TEM) showed that the damage of the mitochondria in the LPS+MNCs group was lighter than that in the LPS group. Noteworthily, the renal Nrf2/HO-1 pathway was activated and autophagy was enhanced after hUCBMNC injection. ML385 could partly reverse the renoprotective effect of hUCBMNCs, which could demonstrate that Nrf2 participated in the protection of hUCBMNCs. Cell experiments showed that increasing the expression level of Nrf2 could alleviate LPS-induced cell injury by increasing the autophagy level and decreasing the injury of the mitochondria in HK-2 cells.
All results suggest that hUCBMNCs can protect against LPS-induced AKI via the Nrf2 pathway. Activating Nrf2 can upregulate autophagy to protect LPS-induced cell injury.
急性肾损伤（AKI）是脓毒症常见的并发症之一。迄今为止，脓毒症相关性急性肾损伤尚无有效的治疗方法。最近的研究表明，人脐带血单个核细胞（hUCBMNCs）除了治疗血液系统恶性肿瘤外，对其他疾病也显示出良好的治疗效果。但hUCBMNCs能否预防脓毒症相关性急性肾损伤及其潜在机制尚不清楚。
建立脂多糖（LPS）诱导的急性肾损伤大鼠模型，并注射hUCBMNCs进行急性肾损伤的防治。使用特异性核因子E2相关因子2（Nrf2）抑制剂ML385使Nrf2沉默。进行细胞实验以阐述Nrf2通路的保护机制。
建立了有效的LPS诱导的急性肾损伤模型。与仅注射LPS的大鼠相比，注射hUCBMNCs后肾组织中的炎症、活性氧（ROS）水平和细胞凋亡明显减轻。病理检查还表明，与LPS组大鼠相比，LPS+MNCs组肾组织损伤明显缓解。透射电子显微镜（TEM）显示，LPS+MNCs组线粒体的损伤比LPS组轻。值得注意的是，注射hUCBMNCs后肾Nrf2/HO-1通路被激活，自噬增强。ML385可部分逆转hUCBMNCs的肾保护作用，这表明Nrf2参与了hUCBMNCs的保护作用。细胞实验表明，提高Nrf2的表达水平可通过提高自噬水平和减少HK-2细胞中线粒体的损伤来减轻LPS诱导的细胞损伤。
所有结果表明，hUCBMNCs可通过Nrf2通路预防LPS诱导的急性肾损伤。激活Nrf2可上调自噬以保护LPS诱导的细胞损伤。
