Preventive And Therapeutic Effects Of Suramin On Sepsis Induced Mouse Model Of Acute Lung Injury And Its Molecular Mechanism

Objective:Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, the lung as sepsis in the pathological process one of the most easily affected target organ, its research value is widely concerned. Suramin has a broad spectrum of biological effect, especially plays an important immune regulation in anti-inflammatory and antiapoptotic by influencing the expression of NF-κB and the release of inflammatory cytokines and so on. Therefore, the purpose of this research is to study the preventive and therapeutic effects of suramin on sepsis-induced mouse model of acute lung injury and its molecular mechanism.Methods:24 healthy male C57BL/6 mice were randomly divided into two groups:Control group and suramin group. Saline or suramin (10 mg/kg) was injected in vein 30 min before LPS infusion. LPS (5 mg/kg, iv) induced acute lung injury model was used in this study. The severity of lung injury was evaluated using haematoxylin-eosin (HE) staining after the injection of LPS for 0,24 and 72 hours. The expression of TNF-a and IL-6 mRNA levels were also detected by RT-PCR. In vitro, THP-1 cells were stimulated by LPS (100 ng/ml) with saline or suramin pre-treatment. The expressions of p-ERK1/2、p-JNK and p-p38 were analyzed by Western blot at 10 min,20 min and 30 min after LPS insult.Results:Compared with the saline group, the lung tissues injury were significantly decreased in the suramin group of 72 hours after the injection of LPS (P<0.01). The expressions of TNF-a (P<0.01) and IL-6 (P<0.01) mRNA were also obviously reduced in suramin group after the injection of LPS for 24 hours. The expression levels of p-ERK1/2> p-JNK and p-p38 were obviously down-regulated by suramin at 10 min、 20 min and 30 min after LPS stimulation.Conclusion:Suramin protected LPS-induced acute lung injury through down-regulating the expression of pro-inflammatory factors, which was closely relative to the inhibition of the MAPK pathway.