MESENCHYMAL STEM CELLS AMELIORATE SEPSIS-ASSOCIATED ACUTE KIDNEY INJURY IN MICE
MESENCHYMAL STEM CELLS AMELIORATE SEPSIS-ASSOCIATED ACUTE KIDNEY INJURY IN MICE
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DOI：
10.1097/shk.0000000000000080
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发表时间：
2014-02-01
期刊：
影响因子：
3.1
通讯作者：
Chen, Xiang-mei
中科院分区：
文献类型：
--
作者：
Luo, Cong-juan;Zhang, Fu-jian;Chen, Xiang-mei
目的：重症监护医学在过去的几十年里取得了重大进展。然而，脓毒症患者的死亡率仍然很高，尤其是急性肾损伤（阿基）患者。间充质干细胞（MSC）具有改善缺血再灌注肾损伤的能力，但其是否具有减少脓毒症相关阿基的能力仍是未知的。研究方法：雄性C57 BL/6小鼠进行盲肠结扎和穿刺手术以诱导脓毒症，然后在手术后3小时接受生理盐水或MSC（静脉注射1 × 10（6）个细胞）。结果：盲肠结扎穿孔术后24 h内，脓毒症小鼠发生肾损伤，死亡率较高。骨髓间充质干细胞治疗降低血清肌酐和血尿素氮水平，改善肾小管功能的恢复。肾组织中的白细胞介素6（IL-6）、IL-17、肿瘤坏死因子α、干扰素γ、CXCL 1、CXCL 2、CXCL 5、CCL 2和CCL 3的mRNA水平在MSC处理后显著降低。骨髓间充质干细胞注射后，肾脏中的神经细胞浸润和血液细菌载量减少。此外，用MSC治疗的小鼠的存活率高于盐水治疗组。注射的MSCs主要定位于肺、脾和腹腔淋巴结中，但不定位于肾脏中。结论：骨髓间充质干细胞治疗可以减轻脓毒症相关的阿基并提高多微生物脓毒症小鼠的生存率。这些作用可能是通过抑制IL-17分泌以及平衡促炎和抗炎状态来介导的。间充质干细胞可能是一种潜在的新的治疗剂，用于预防或减少脓毒症相关的阿基。
Objective: Significant progress has been made in critical care medicine during the past several decades. However, the mortality rate is still high in patients with sepsis, especially with acute kidney injury (AKI). Mesenchymal stem cells (MSCs) possess an ability to ameliorate renal injury from ischemia-reperfusion, but it is still unknown whether they have the ability to reduce sepsis-associated AKI. Methods: Male C57BL/6 mice underwent cecal ligation and puncture operation to induce sepsis and then received either normal saline or MSCs (1 x 10(6) cells intravenously) 3 h after surgery. Results: Within 24 h after cecal ligation and puncture operation, the septic mice developed kidney injury and exhibited a higher mortality. Treatment with MSCs decreased serum creatinine and blood urea nitrogen levels and improved recovery of tubular function. mRNA levels of interleukin 6 (IL-6), IL-17, tumor necrosis factor alpha, interferon gamma, CXCL1, CXCL2, CXCL5, CCL2, and CCL3 in kidney tissue were dramatically decreased after MSC treatment. Neutrophil infiltration in kidney and blood bacterial loads were attenuated after MSC injection. Moreover, mice treated with MSCs had a higher survival rate than the saline treatment group. Injected MSCs were mainly localized in the lungs, spleen, and abdominal cavity lymph node, but not in the kidneys. Conclusions: Treatment with MSCs can alleviate sepsis-associated AKI and improve survival in mice with polymicrobial sepsis. These effects may be mediated by the inhibition of IL-17 secretion and balance of the proinflammatory and anti-inflammatory states. Mesenchymal stem cells may be a potential new therapeutic agent for the prevention or reduction of sepsis-associated AKI.