Aerosol inhalation of a hydrogen-rich solution restored septic renal function.
Aerosol inhalation of a hydrogen-rich solution restored septic renal function.
复制标题
气溶胶吸入富氢溶液可恢复脓毒症肾功能
DOI：
10.18632/aging.102542
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Hei Ziqing
中科院分区：
文献类型：
--
作者：
Yao Weifeng;Guo Anshun;Han Xue;Wu Shan;Chen Chaojin;Luo Chenfang;Li Haobo;Li Shangrong;Hei Ziqing
败血症相关的急性肾损伤(AKI)已知是由炎症引起的。我们探讨了雾化吸入富氢溶液(HRS；氢气在盐水中溶解至饱和)对败血症AKI小鼠模型的肾脏保护作用。通过盲肠结扎和穿孔18h诱导感染性AKI。AKI发生于脓毒症早期，表现为血尿素氮和血肌酐水平升高，病理改变，肾脏纤维化和肾小管上皮细胞凋亡，并伴有肾组织巨噬细胞浸润和M1巨噬细胞相关的促炎细胞因子(IL-6和肿瘤坏死因子-α)的产生。雾化吸入HRS可增加肾组织中抗炎细胞因子(IL-4和IL-13)的表达，促进巨噬细胞向M2型极化，从而产生额外的抗炎细胞因子(IL-10和转化生长因子-β)。最终，雾化吸入HRS保护了肾脏，提高了脓毒症小鼠的存活率。HRS能促进脂多糖刺激的RAW 264.7细胞M2巨噬细胞极化。转化生长因子-β1受体抑制剂SB-431542可部分逆转HRS对小鼠肾功能、肾间质纤维化、肾小管上皮细胞凋亡和衰老的影响。因此，HRS雾化吸入对败血症AKI的肾脏保护和炎症减轻非常有用。
Sepsis-related acute kidney injury (AKI) is known to be caused by inflammation. We explored the renal protective effects of aerosol inhalation of a hydrogen-rich solution (HRS; hydrogen gas dissolved to saturation in saline) in a mouse model of septic AKI. Septic AKI was induced through 18 hours of cecal ligation and puncture. AKI occurred during the early stage of sepsis, as evidenced by increased blood urea nitrogen and serum creatinine levels, pathological changes, renal fibrosis and renal tubular epithelial cell apoptosis, accompanied by macrophage infiltration and M1 macrophage-associated pro-inflammatory cytokine (Il-6 and Tnf-α) generation in renal tissues. Aerosol inhalation of the HRS increased anti-inflammatory cytokine (Il-4 and Il-13) mRNA levels in renal tissues and promoted macrophage polarization to the M2 type, which generated additional anti-inflammatory cytokines (Il-10 and Tgf-β). Ultimately, aerosol inhalation of HRS protected the kidneys and increased survival among septic mice. HRS was confirmed to promote M2 macrophage polarization in lipopolysaccharide-stimulated RAW 264.7 cells. The TGF-β1 receptor inhibitor SB-431542 partly reversed the effects of HRS on renal function, fibrosis, tubular epithelial cell apoptosis and senescence in mice. Thus, HRS aerosol inhalation appears highly useful for renal protection and inflammation reduction in septic AKI.