Xuebijing Ameliorates Sepsis-Induced Lung Injury by Downregulating HMGB1 and RAGE Expressions in Mice

Abstract

Xuebijing (XBJ) injection, a traditional Chinese medicine, has been reported as a promising approach in the treatment of sepsis in China. However, its actual molecular mechanisms in sepsis-induced lung injury are yet unknown. Therefore, this study aimed to investigate the beneficial effects of XBJ on inflammation and the underlying mechanisms in a model of caecal ligation and puncture-(CLP-) induced lung injury. The mice were divided into CLP group, CLP+XBJ group (XBJ, 4 mL/kg per 12 hours), and sham group. The molecular and histological examinations were performed on the lung, serum, and bronchoalveolar lavage (BAL) fluid samples of mice at the points of 6, 24, and 48 hours after CLP. The results show that XBJ reduces morphological destruction and neutrophil infiltration in the alveolar space and lung wet/dry weight ratio, which improves mortality of CLP-induced lung injury. Meanwhile, XBJ treatment downregulates high mobility group box protein 1 (HMGB1) and the receptor for advanced glycation end products (RAGE) expression, as well as neutrophil counts, production of IL-1β, IL-6, and TNF-α in the BAL fluids. In conclusion, these results indicate that XBJ may reduce the mortality through inhibiting proinflammatory cytokines secretion mediated by HMGB1/RAGE axis.

Clinical investigation of the efficacy and toxicity of apatinib (YN968D1) in stage III/IV non‐small cell lung cancer after second‐line chemotherapy treatment: A retrospective study

“…Apatinib, also known as YN968D1, is a small molecule TKI that mainly targets VEGFR‐2 through the intracellular ATP‐binding site that inhibits all VEGF‐stimulated endothelial cell migration and proliferation, decreases tumor microvascular density, and promotes apoptosis . On 17 October 17, 2014, apatinib was approved by the cFDA as a third or subsequent‐line therapy for advanced or metastatic chemo‐refractory gastric cancer . Both preclinical and clinical studies have shown that apatinib has promising efficacy, convenient oral administration methods, and manageable AEs in the treatment of a variety of solid tumors …”

“…[46][47][48] On 17 October 17, 2014, apatinib was approved by the cFDA as a third or subsequent-line therapy for advanced or metastatic chemo-refractory gastric cancer. 49 Both preclinical and clinical studies have shown that apatinib has promising efficacy, convenient oral administration methods, and manageable AEs in the treatment of a variety of solid tumors. 26,32,33,50 The efficacy of apatinib as a second or subsequent-line therapy in patients with advanced NSCLC has been investigated in several studies.…”

Inhibitory effect of post-hemorrhagic shock mesenteric lymph drainage on the HMGB1 and RAGE in mouse kidney

“…Combined with the HMGB1, RAGE, one of the surface receptors in cytomembrane, also can trigger the development of inflammatory cascade including mitogen-activated protein kinases (MAPK), TLR4 and NF-kB translocation. [21][22][23][24][25] Previous studies have shown that RAGE could mediate the HMGB1 activation of TLR4 and TLR2 signal transduction and the development of ALI after hemorrhagic shock. 15,16,18 The present study demonstrated that both mRNA and protein expressions of RAGE are increased in hemorrhagic shocked kidneys and that these increases are abolished by PHSML drainage.…”

New Biomarkers of Sepsis with Clinical Relevance

“…Further studies support this assertion, such as the study by Matsumoto et al [40] demonstrated that the sRAGE serum level of patients with sepsis increases directly proportional to the severity of the disease, suggesting that sRAGE reflects on the RAGE's signaling pathway inducing an excessive inflammatory response involved in endothelial injury and coagulopathy. In the same year, Wang et al [41] demonstrated that the decrease in sRAGE levels in mice results in improved sepsis-induced lung damage, thus decreasing mortality in this condition. Another study by Narvaez-Rivera et al [36] demonstrated in 2015 that sRAGE's level in the plasma is high in patients with communityacquired pneumonia associated with sepsis and is also an independent factor for the likelihood of a fatal outcome.…”