Continuous Blood Purification Ameliorates Multiple Organ Failure Through Inhibiting the Activation of the P38 MAPK Signaling Pathway in a Rat Model.

BACKGROUND/AIMS: Multiple organ failure (MOF) is a primary threat to the survival of patients with systemic inflammation. Blood purification is employed in the treatment of MOF, as an artificial kidney or artificial liver. This study focuses on the effects of continuous blood purification (CBP) on ameliorating MOF through regulating the p38 mitogen-activated protein kinase (MAPK) signaling pathway in a rat model. METHODS: A rat model of MOF was successfully established by endotoxin injection after hemorrhagic shock resuscitation. The mRNA expressions of inducible nitric oxide synthase (iNOS) and p38 MAPK of liver, kidney, and lung tissues in each group were measured by RT-qPCR at each measuring time point. To evaluate the activation of p38 MAPK signaling pathway, protein levels of phosphorylated p38 (p-p38) MAPK and p38 MAPK was measured by western blot analysis. The serum levels of nitric oxide and TNF-α were determined. RESULTS: After CBP treatment, the levels of SGPT, SGOT, Cr, and BUN were significantly declined, while the PaO2 value was increased. Expressions of p38 MAPK mRNA, iNOS mRNA, p-p38 MAPK protein and p38 MAPK protein, and nitric oxide and TNF-α levels were markedly elevated in MOF, an effect blunted by CPB. Meanwhile, pathological sections of liver, kidney, and lung tissues after CPB treatment ameliorated swelling and inflammation. CONCLUSION: Our study proved that CBP could downregulate the p38 MAPK signaling pathway, suppress iNOS expression, reduced the serum levels of nitric oxide and TNF-α, thus ameliorate symptom of MOF.

MicroRNA-30e promotes hepatocyte proliferation and inhibits apoptosis in cecal ligation and puncture-induced sepsis through the JAK/STAT signaling pathway by binding to FOSL2.

INTRODUCTION: Hepatocyte proliferation and apoptosis are critical cellular behaviors in rat liver as a result of a liver injury. Herein, we performed this study in order to evaluate the role of miR-30e and its target Fos-Related Antigen-2 (FOSL2) in septic rats through the JAK/STAT signaling pathway. METHODS: Rat models of sepsis were induced by cecal ligation and puncture. Enzyme-linked immunosorbent assay (ELISA) was performed to access serum levels of lipopolysaccharide (LPS), inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to confirm the successful establishment of the model. The hepatocytes were subject to miR-30e mimics, miR-30e inhibitors or siRNA-FOSL2. The expressions of miR-30e, FOSL2, apoptosis- and, JAK/STAT signaling pathway-related genes in liver tissues and hepatocytes were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. MTT assay and flow cytometry were performed to evaluate hepatocyte viability and apoptosis, respectively. RESULTS: The results obtained revealed that in the septic rats, serum levels of inflammatory factors, LPS, ALT and AST, as well as the expression of FOSL2 were elevated and the JAK/STAT signaling pathway was activated, while there was a reduction in the expression of miR-30e. An initial bioinformatics prediction followed by a confirmatory dual-luciferase reporter assay determined that miR-30e targeted and negatively regulated FOSL2 expression. MiR-30e inhibited the activation of JSK2/STAT3 signaling pathway by reducing FOSL2 expression, while miR-30e enhanced hepatocyte proliferation and decreased hepatocyte cell apoptosis in septic rats. CONCLUSION: These findings indicated that miR-30e may serve as an independent therapeutic target for sepsis, due to its ability to inhibit apoptosis and induce proliferation of hepatocytes by targeted inhibition of FOSL2 through the JAK/STAT signaling pathway.

Astilbin alleviates sepsis-induced acute lung injury by inhibiting the expression of macrophage inhibitory factor in rats.

Sepsis is a systemic inflammatory response syndrome caused by severe infections. Astilbin is a dihydroflavonol derivative found in many medicinal and food plants with multiple pharmacological functions. To investigate the effects of astilbin on sepsis-induced acute lung injury (ALI), cecal ligation and puncture was performed on rats to establish a sepsis-induced ALI model; these rats were then treated with astilbin at different concentrations. Lung injury scores, including lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration were determined to evaluate the effects of astilbin on sepsis-induced ALI. We found that astilbin treatment significantly attenuates sepsis-induced lung injury and improves survival rate, lung injury scores, lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration. Astilbin treatment also dramatically decreased the production of inflammatory cytokines and chemokines in bronchoalveolar lavage fluid. Further, astilbin treatment inhibited the expression and production of macrophage inhibitory factor (MIF), which inhibits the inflammatory response. Collectively, these data suggest that astilbin has a protective effect against sepsis-induced ALI by inhibiting MIF-mediated inflammatory responses. This study provides a molecular basis for astilbin as a new medical treatment for sepsis-induced ALI.

Effects of right atrial and ventricular DDD pacing on cardiac function and ventricular contraction synchrony.

BACKGROUND: Right ventricular apical pacing has been reported to reduce cardiac performance. But there are few reports on the effects of dual chamber (DDD) pacing on cardiac function compared to sinus rhythm. In this study, we evaluated the effects of right atrial and ventricular DDD pacing on cardiac function and ventricular contraction synchrony using equilibrium radionuclide angiography. METHODS: Ten patients implanted with a right atrial and ventricular DDD pacemaker underwent equilibrium radionuclide angiography. The scintigraphic data were obtained during sinus rhythm and pacing rhythm. Cardiac function parameters were obtained semimanually. Phase analysis was used to study the ventricular activation sequence and ventricular synchrony. RESULTS: The left ventricular 1/3 ejection fraction decreased significantly during pacing compared with that during sinus rhythm [(23.4 +/- 6.1)% vs (27.7 +/- 4.5)%, P = 0.01]. Regional ejection fraction also decreased during pacing, although the difference was not statistically significant. Phase analysis showed that the right ventricle was activated earlier than the left ventricle during pacing, and that the phase shift was significantly greater during pacing than that during sinus rhythm [64.13 degrees +/- 16.80 degrees vs 52.88 degrees +/- 9.26 degrees, P = 0.007]. The activation of both ventricles occurred simultaneously during sinus rhythm, with the activation sequence from proximal septum or base of left ventricle to apex. The earliest activation during pacing occurred at the right ventricular apex, and subsequently spread to the base and left ventricle. CONCLUSION: Right atrial and ventricular DDD pacing impairs left ventricular systolic function and ventricular synchrony.