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

Abstract

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.

The effect of continuous blood purification on P38MAPK signaling pathway in patients with multiple organ dysfunction syndrome

“…Various stimuli, such as pro‐inflammatory factors, cytokines, and cellular stress, can phosphorylate p38MAPK via the protein kinase cascade. Phosphorylated p38MAPK will get access to the nucleus, regulating the inflammatory response and cellular immune response . In our study, we found out that the protein level of p‐p38MAPK was significantly higher in the blood sample of patients with MODS and the p‐p38MAPK induced by serum from patients with MODS was also significantly increased compared to control group ( P < 0.05).…”

Extracorporeal Blood Purification in Burns: For Whom, Why, and How?

“…A study shows that inhibition of p38 mitogen-activated protein kinase largely improves resulting vascular dysfunction [ 5 ]. Other studies enhanced that continuous BP could potentially downregulate the p38 MAPK signaling pathway, suppress inducible nitric oxide synthase expression, reduce the serum levels of nitric oxide and TNF-α, and thus improve symptoms of multiple organ failure [ 36 , 37 ].…”