microRNA-23b regulates the expression of inflammatory factors in vascular endothelial cells during sepsis.

miR-23b is a multifunctional microRNA that contributes to the regulation of multiple signaling pathways. It has been reported that miR-23b prevents multiple autoimmune diseases through the regulation of inflammatory cytokine pathways. In addition, the function and underlying mechanisms of miR-23b on sepsis are currently being investigated. In the present study, miR-23b inhibitor and mimics sequences were transfected into human vascular endothelial cells to inhibit and upregulate the expression of miR-23b, respectively. In addition, respective negative control (NC) sequences were transfected. The expression of miR-23b was found to be downregulated in the cells transfected with the mimics NC or inhibitor NC sequences following stimulation with lipopolysaccharide (LPS; P<0.01); however, higher expression levels were maintained in the cells transfected with the mimics sequence and very low levels were observed in the cells transfected with the inhibitor sequence. In addition, the expression levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, E-selectin and vascular cell adhesion molecule (VCAM)-1 were shown to increase following induction by LPS in the cells transfected with inhibitor/mimics NC sequences (P<0.05). However, the expression levels of these inflammatory factors decreased in the cells transfected with the mimics sequence, and increased to a greater degree in the cells transfected with the inhibitor sequence, as compared with the inhibitor NC sequences (P<0.05). Therefore, miR-23b may play a significant role in the pathogenesis and progression of sepsis by inhibiting the expression of inflammatory factors, including NF-κB, TNF-α, IL-6, ICAM-1, E-selectin and VCAM-1.

[Propofol ameliorates rat liver ischemia-reperfusion injury possibly by inhibiting nuclear factor-kappaB expression].

OBJECTIVE: To explore the role of nuclear factor-kappaB (NF-kappaB) in the protective effects of propofol against liver ischemia-reperfusion (IR) injury. METHODS: Forty male rats were randomized into 4 equal groups, namely the sham operation (N) group, IR group with hepatic IR injury (induced by ischemia of the left, right and median hepatic lobes for 1 h followed by reperfusion for 2 h), propofol (P) group with sham operation and propofol perfusion at 10 mg kg(-1) h(-1), and propofol treatment (PIR) group with IR injury and propofol perfusion. RT-PCR was used to detect the transcription level of NF-kappaB, and Western blotting was used for assaying NF-kappaB protein expression in the liver. RESULTS: Compared with either the N or the P group, the IR group showed obvious swelling, fatty degeneration and scatter focal necrosis of the hepatocytes as well as mild congestion in the hepatic sinusoid, with significantly increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and NF-kappaB expressions at both mRNA and protein levels (P<0.05). In the PIR group, the histopathological changes of the liver was lessened as compared with the IR group, and ALT and AST elevation was significantly inhibited (P<0.05) as was the protein expression of NF-kappaB (P<0.05), but NF-kappaB transcription level was further enhanced (P<0.05). CONCLUSION: Propofol can protect the liver from IR injury possibly by inhibiting NF-kappaB expression.

[Role of Janus kinase/signal transducer and activator of transcription pathway in mediating mRNA expression of high mobility group box1 protein in the liver in septic rats].

OBJECTIVE: To investigate the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in mediating mRNA expression of high mobility group box 1 protein (HMGB1) in the liver in septic rats. METHODS: Using a sepsis model of cecal ligation and puncture (CLP), 98 male Wistar rats were randomly divided into normal control group (n=10), CLP group (n=40), AG490 treatment group (n=24), and Rapamycin (RPM) treatment group (n=24). At serial time points animals in each group were sacrificed, and blood as well as hepatic tissue samples were harvested to determine HMGB1 mRNA expression and serum aspartate aminotransferase (AST) as well as alanine aminotransferase (ALT) contents. RESULTS: Compared with normal controls, HMGB1 mRNA levels were significantly increased in the liver during 6-48 hours after CLP (P<0.01), and serum AST and ALT contents were significantly elevated at different time points respectively (P<0.05 or P<0.01). Treatment with AG490 and RPM could markedly inhibit HMGB1 mRNA expression in the liver at 24 hours, 48 hours, 6 hours and 24 hours after CLP, respectively. In addition, compared to CLP group, serum AST and ALT contents in both treatment groups could be markedly reduced at various intervals after CLP (P<0.05 or P<0.01). CONCLUSION: These data suggest that the activation of JAK/STAT pathway might be involved in mediating up-regulation of HMGB1 mRNA expression in the liver in CLP-induced sepsis. Treatment with inhibitors of JAK/STAT pathway could markedly down-regulate HMGB1 mRNA expression and attenuate acute liver injury associated with sepsis.