Protective effects of Doxycycline on endotoxin-induced acute lung injury in rats

AIM:To explore the mechanism of doxycycline in the treatment of endotoxin-induced acute lung injury(ALI) in rats.METHODS:Seventy-two male SD rats were randomly divided into 3 groups:control group(n=24),ALI group(n=24) and treatment group(n=24).The rats in the ALI group were treated with lipopolysaccharide(LPS) by intratracheal injection to induce acute lung injury,followed by injection of 1 mL normal saline,the rats in the treatment group were first treated with LPS and then with Doxycycline 20 mg/kg(dissolved in 1 mL NS)and the rats in the control group were treated with normal saline.The animals in the 3 groups were killed 1,2,4 and 8 h after operation and then blood gas was monitored and the lung tissue wet/dry weight(W/D) was detected.The histopathology of the lung injury was observed by light microscope,and the expressions of matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase-9(MMP-9) proteins in the lung tissues were detected by immunohistochemistry.RESULTS:Arterial partial pressure of oxygen(PaO2) in the ALI group and the treatment group decreased rapidly after the rats were treated with LPS by intratracheal injection.PaO2 in the ALI group was lower than that in the treatment group(P0.05,P0.01).The W/D value of the ALI and the treatment group was significantly higher(P0.05),and the W/D value of the treatment group was lower than that of the ALI group,with statistical difference(P0.05,P0.01).The degree of lung injury,including lung swelling,neutrophil cells infiltration and hemorrhage,in the treatment groups was milder.The expressions of MMP-2 and MMP-9 in lung tissues in the ALI group rapidly increased after intratracheal injection and reached peak at 4 h.The expressions of MMP-2 and MMP-9 in the ALI group were higher than those in the treatment group at all time points(P0.05,P0.01).No significant changes were observed in the control group at various time points.CONCLUSION:Doxycycline inhibits the expressions of MMP-2 and MMP-9 in the lung tissue,improves oxygenation in respiratory and relieves the damage of endotoxin-induced ALI in rats.