白藜芦醇通过使长链非编码RNA MALAT1/微小RNA-205轴失活来减轻脓毒症诱导的急性肾损伤。
Resveratrol alleviates sepsis-induced acute kidney injury by deactivating the lncRNA MALAT1/MiR-205 axis.
作者信息
Wang Biao, Wang Yijun, Xu Ke, Zeng Zhenhua, Xu Ziqiang, Yue Dongyou, Li Tao, Luo Jihui, Liu Junhong, Yuan Jiemin
机构信息
The Second Hospital, University of South China, China.
Chenzhou No. 1 People's Hospital, China.
出版信息
Cent Eur J Immunol. 2021;46(3):295-304. doi: 10.5114/ceji.2021.109195. Epub 2021 Oct 19.
INTRODUCTION
Resveratrol plays a protective role against sepsis development, and the long noncoding RNA (lncRNA) MALAT1 is an inflammation-relevant biomarker. This investigation attempted to reveal whether resveratrol attenuated inflammation of sepsis-induced acute kidney injury (AKI) by regulating MALAT1.
MATERIAL AND METHODS
In total 120 rats were divided into a control group (n = 20), a Sham group (n = 20), a sepsis group (n = 40) and a resveratrol group (n = 40), and serum levels of inflammatory cytokines and AKI biomarkers were determined. An equal number of rats under identical treatments were, additionally, tracked for their survival, and the serum level of lncRNA MALAT1 was measured by RT-PCR. Moreover, septic cell models were constructed by treating HK-2 cells with lipopolysaccharide (LPS), and tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 levels released by the cells were determined with ELISA.
RESULTS
Resveratrol treatment significantly brought down serum levels of inflammatory cytokines (i.e. TNF-α, IL-1β and IL-6), kidney function indicators (i.e. Scr, blood urea nitrogen [BUN] and Scys C), AKI biomarkers (i.e. NGAL and KIM-1) and MALAT1 in cecal ligation and puncture (CLP)-induced septic model rats (all p < 0.05), and the life span of septic rats was elongated by resveratrol treatment (p < 0.05). Viability and cytokine release of LPS-treated HK2 cells were rescued by resveratrol (p < 0.05), which was accompanied by a marked fall of MALAT1 expression (p < 0.05). In addition, si-MALAT1 diminished viability and suppressed cytokine release of HK2 cells, while pcDNA3.1-MALAT1 hindered the impact of resveratrol on the inflammatory response of HK2 cells (p < 0.05). Ultimately, miR-205, a protective molecule in sepsis-relevant AKI, was down-regulated by resveratrol and si-MALAT1 (p < 0.05).
CONCLUSIONS
Resveratrol relieved sepsis-induced AKI by restraining the lncRNA MALAT1/miR-205 axis.
引言
白藜芦醇对脓毒症的发展具有保护作用，长链非编码RNA（lncRNA）MALAT1是一种与炎症相关的生物标志物。本研究试图揭示白藜芦醇是否通过调节MALAT1减轻脓毒症诱导的急性肾损伤（AKI）的炎症反应。
材料与方法
将120只大鼠分为对照组（n = 20）、假手术组（n = 20）、脓毒症组（n = 40）和白藜芦醇组（n = 40），检测血清炎症细胞因子和AKI生物标志物水平。另外，对相同处理下的同等数量大鼠进行生存追踪，并通过RT-PCR检测lncRNA MALAT1的血清水平。此外，通过用脂多糖（LPS）处理HK-2细胞构建脓毒症细胞模型，并用ELISA法测定细胞释放的肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1β、IL-6水平。
结果
在盲肠结扎穿孔（CLP）诱导的脓毒症模型大鼠中，白藜芦醇治疗显著降低了血清炎症细胞因子（即TNF-α、IL-1β和IL-6）、肾功能指标（即Scr、血尿素氮[BUN]和胱抑素C）、AKI生物标志物（即中性粒细胞明胶酶相关脂质运载蛋白[NGAL]和肾损伤分子-1[KIM-1]）以及MALAT1的水平（均p < 0.05），并且白藜芦醇治疗延长了脓毒症大鼠的寿命（p < 0.05）。白藜芦醇挽救了LPS处理的HK2细胞的活力和细胞因子释放（p < 0.05），同时伴随着MALAT1表达的显著下降（p < 0.05）。此外，si-MALAT1降低了HK2细胞的活力并抑制了细胞因子释放，而pcDNA3.1-MALAT1则阻碍了白藜芦醇对HK2细胞炎症反应的影响（p < 0.05）。最终，白藜芦醇和si-MALAT1下调了脓毒症相关AKI中的保护分子miR-
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