Methane-Rich Saline Ameliorates Sepsis-Induced Acute Kidney Injury through Anti-Inflammation, Antioxidative, and Antiapoptosis Effects by Regulating Endoplasmic Reticulum Stress
Methane-Rich Saline Ameliorates Sepsis-Induced Acute Kidney Injury through Anti-Inflammation, Antioxidative, and Antiapoptosis Effects by Regulating Endoplasmic Reticulum Stress
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富含甲烷的盐水通过调节内质网应激的抗炎、抗氧化和抗凋亡作用改善脓毒症引起的急性肾损伤
DOI：
10.1155/2018/4756846
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Zhang, Jingyao
中科院分区：
文献类型：
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作者：
Jia, Yifan;Li, Zeyu;Zhang, Jingyao
败血症诱导的急性肾损伤（AKI）是败血症的严重并发症，是化脓性患者死亡率的重要原因。先前的研究表明，甲烷具有针对动物模型中不同疾病的保护特性。这项研究旨在研究富含甲烷的盐水（MRS）是否具有针对败血症引起的AM的保护作用。通过盲肠结扎和穿刺（CLP）在野生型C57BL/6小鼠中诱导败血症，将小鼠分为三组：假对照组（假），这是一个接受盐腹腹膜内注射（I.P.）治疗（CLP + NS）的手术组，以及与MRS I.P.P.的手术组。治疗（CLP + MRS）。败血症建立后24小时，收集了所有组小鼠的血液和肾脏组织。根据血液尿素氮（BUN）和肌酐（CRE）的血清水平以及组织学分析，其中包括苏木精 - 烯烃（H＆E）染色以及周期性酸 - chiff（PAS）染色，MRS治疗受保护的肾功能和组织受到急性损伤的保护。此外，MRS治疗基于与凋亡相关的蛋白质制造商的水平，包括裂解的caspase-3和裂解PARP，以及Bcl-2/BAX表达和TUNEL染色的水平，从而显着改善了凋亡。此外，内质网（ER）应激相关葡萄糖调节的蛋白78（GRP78）/激活转录因子4（ATF4）/C/EBP同源蛋白（CHOP）/CASPASE-12凋亡信号通路在CLP + MRS组中显着抑制。 MRS治疗后，炎症和氧化应激水平也降低。这些结果表明，MRS有可能通过其抗炎，抗氧化和抗凋亡特性来改善败血症诱导的急性肾脏损伤。
Sepsis-induced acute kidney injury (AKI) is a severe complication of sepsis and an important cause of mortality in septic patients. Previous investigations showed that methane had protective properties against different diseases in animal models. This study is aimed at investigating whether methane-rich saline (MRS) has a protective effect against sepsis-induced AKI. Sepsis was induced in wild-type C57BL/6 mice by cecal ligation and puncture (CLP), and the mice were divided into three groups: a sham control group (sham), a surgery group with saline intraperitoneal injection (i.p.) treatment (CLP + NS), and a surgery group with MRS i.p. treatment (CLP + MRS). 24 h after the establishment of the sepsis, the blood and kidney tissues of mice in all groups were collected. According to the serum levels of blood urea nitrogen (BUN) and creatinine (CRE) and a histologic analysis, which included hematoxylin-eosin (H&E) staining and periodic acid-Schiff (PAS) staining, MRS treatment protected renal function and tissues from acute injury. Additionally, MRS treatment significantly ameliorated apoptosis, based on the levels of apoptosis-related protein makers, including cleaved caspase-3 and cleaved PARP, and the levels of Bcl-2/Bax expression and TUNEL staining. In addition, the endoplasmic reticulum (ER) stress-related glucose-regulated protein 78 (GRP78)/activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP)/caspase-12 apoptosis signaling pathway was significantly suppressed in the CLP + MRS group. The levels of inflammation and oxidative stress were also reduced after MRS treatment. These results showed that MRS has the potential to ameliorate sepsis-induced acute kidney injury through its anti-inflammatory, antioxidative, and antiapoptosis properties.