Yuan Jinling, Hou Kaixiao, Yao Yawen, Du Zhongying, Lu Cao, Yuan Qing, Gao Xueyun
Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing 100124, China.
Nanomaterials (Basel). 2020 Apr 10;10(4):712. doi: 10.3390/nano10040712.
Sepsis-induced acute kidney injury (AKI) with high incidence and mortality rates remains a great challenge in the clinic; thus, novel therapies need to be developed urgently. This complication is associated with an overwhelming systemic inflammatory response. The aim of this study was to evaluate the potential effects and possible mechanisms of gold clusters on septic AKI in vitro. Rat mesangial HBZY-1 cells were treated with peptide-templated gold clusters under lipopolysaccharide (LPS) stimulation. The LPS-induced expression of pro-inflammatory cytokines was measured, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6). Our data showed that the LPS-induced transcription and secretion of these cytokines were suppressed by pretreatment of gold clusters in a dose-dependent manner. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) also play key roles in septic AKI and both of them are induced upon LPS-stimulation in mesangial cells. Our results further showed that pretreatment with gold clusters dramatically inhibited the LPS-stimulated transcription and expression of COX2 and iNOS, and the subsequent prostaglandin E2 (PGE2) and nitric oxide (NO) production in HBZY-1 cells. Since these factors are involved in the NF-κB pathway upon LPS stimulation, the potential roles of gold clusters on the NF-κB pathway were further determined. We found that LPS-induced NF-κB activation was suppressed in gold clusters-pretreated HBZY-1 cells. These results demonstrated that gold clusters can attenuate LPS-induced inflammation in mesangial cells, probably via inhibiting the activation of the NF-κB pathway, suggesting a potential therapeutic approach for septic AKI.
脓毒症诱导的急性肾损伤（AKI）发病率和死亡率高，仍然是临床上的一大挑战；因此，迫切需要开发新的治疗方法。这种并发症与压倒性的全身炎症反应有关。本研究的目的是在体外评估金簇对脓毒症AKI的潜在作用和可能机制。在脂多糖（LPS）刺激下，用肽模板化金簇处理大鼠系膜HBZY-1细胞。检测LPS诱导的促炎细胞因子的表达，包括肿瘤坏死因子α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）。我们的数据表明，金簇预处理以剂量依赖性方式抑制了这些细胞因子的LPS诱导的转录和分泌。环氧合酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）在脓毒症AKI中也起关键作用，它们在系膜细胞中受到LPS刺激后均被诱导。我们的结果进一步表明，金簇预处理显著抑制了LPS刺激的HBZY-1细胞中COX2和iNOS的转录和表达，以及随后前列腺素E2（PGE2）和一氧化氮（NO）的产生。由于这些因子在LPS刺激后参与NF-κB途径，进一步确定了金簇对NF-κB途径的潜在作用。我们发现，在金簇预处理的HBZY-1细胞中，LPS诱导的NF-κB激活受到抑制。这些结果表明，金簇可能通过抑制NF-κB途径的激活来减轻LPS诱导的系膜细胞炎症，提示了一种治疗脓毒症AKI的潜在方法。
