The Effects Of Acid-sensing Na +/h + Exchanger Inhibitor Cariporide On Lps-induced Acute Lung Injury In Rats

Objective: To investigate effects of acid-sensing Na+/H+-exchanger inhibitor Cariporide on LPS-induced acute lung injury in rats as well as provide help to explore new medicine for prophylaxis and treatment on ALI/ARDS.Method: Twenty-four SD rats of 6to 8-week-old were randomly divided into 3 groups (n=8, each): control group (A group), LPS group (B group) and LPS+Cariporide group(C group). The rats in group were intravenously injected normal saline 0.5ml via femoral vein, the rats in group B and C were given LPS 10 mg per kg through femoral vein to establish animal model of acute lung injury, 3 mg per kg Cariporide was given in group C two hours later. Blood was taken from abdominal aorta to measure blood-gas analysis in the next 4 hours. All rats were killed by blood letting, specimens were taken from right lung to observe pathological changes, apoptosis and the level of Bcl-2 mRNA. Measurements done include the level of TNF-α, IL-8, MPO and MDA. SPSS 13.0 was applied to analyze the results of test, P<0.05 was considered that there were significant differences between three groups.Results: Compared to the LPS group, the wet-dry weight ratio and the degree of lung injury in C group reduced significantly, the levels of AI ,MPO ,MDA, TNF-αor IL-8 decreased either (P<0.01),meanwhile, the levels of Bcl-2 mRNA increased significantly (P <0.01).Conclusion: Acid-sensing Na +/H +-exchanger inhibitor Cariporide can effectively reduce the degree of lung injury induced by LPS, and further improve lung functions. The protection mechanism is mainly associated with the regulations of intracellular pH and sodium level which effect on the activity of neutrophil, release of TNF-αand IL-8 in macrophage, alleviation of apoptosis or edema in AT-II cells.