Experimental Study of Renin-Angiotensin System Changes And Its Intervention on Acute Lung Injury/Acute Respiratory Distress Syndrome Rat

TIAN Xiao-jun,ZHU Feng(Intensive Care Unit,the Second People's Hospital of Jingzhou City,Jingzhou 434000,China)

Acute lung injury/acute respiratory distress syndrome(ALI/ARDS);;Renin-Angiotensin System(RAS);;Losartan;;Angiotensin-converting enzyme(ACE);;Lung wet/dry weight ratio(W/D)

Objective:We established oleic acid induced ALI/ARDS animal model to observe the variation of the renin-angiotensin system(RAS) in the acute lung injury(ALI) and acute respiratoryjdistress syndrome CARDS),we hoped that through this series of experiments to explore new therapy ways of ALI/ARDS.Method:PartⅠ:The changes of RAS on ALI/ARDS models:we assessed the acute lung injury by symptoms,arterial blood gas analysis,lung wet/dry weight ratio(W/D) and other indicators of lung pathology 6 hours after mold was built;By UV spectrophotometry and radioimmunoassay system we determined several key RAS enzyme(ACE,ACE2 and AngⅡ) > and studied its variation.PartⅡ:The impacts of RAS drugs on ALI/ARDS:we gave a separate intraperitoneal injection of captopril(ACE antagonist),recombinant rat ACE2(rm ACE2) and losartan(AngⅡof the ATI receptor blocker),then observed their therapeutic effect,in particular,observed the therapeutic effect of losartan.PartⅢ:The possible mechanisms of losartan prevented lung injury:Obser- vating expression of ALI/ARDS plasma inflammatory factors such as TNF-α,IL-6.Results:PartⅠ: ALI/ARDS in animal models of RAS changes:?The model was successful.Compared with control rats significantly increased lung water content(W/D:6.71±0.64 vs 4.02±0.10,P <0.01),oxygenation index decreased significantly hypoxic(PaO_2/FiO_2:267±19 vs 450±15,P <0.01),and lung pathology apparent lung injury change.?Compared with the control group,oleic acid group decreased expression of ACE2 in rat plasma,in losartan group,not only the expression of ACE2 was significantly increased,but also the expression of ACE was corresponding decrease.?The plasma in the oleic acid group was significantly higher amount of AngⅡ,and joined the RAS-related changes after drug AngⅡ;with the oleic acid group,losartan could inhibit the generation of AngⅡin vivo (76.50±29.21 vs 118.92±45.48).PartⅡ:RAS drugs on ALI/ARDS effects:?Compared with the oleic acid group,the lung W/D of the captopril group significantly reduced(5.35±0.25 vs 6.06±0.22,P <0.05),the rmACE2 group also reduced(6.33±0.32 vs 6.71±0.64,P =0.542),but there was not significant statistical difference.The losartan administration had led to a most significant decrease in W/D(5.35±0.25,P <0.01).?Losartan could improve the seven days survival rate of ALI/ARDS rats.Conclusion:①RAS was active,expressing as ACE,ACE2 and AngⅡmake a significant change,ACE played a positive effect in generating AngⅡ,ACE2 played a negative effect.②Intervening RAS could affect ALI/ARDS pathological process,and improve part of lung injury.The role of losartan was the most evident,which could finally improve seven days survival.③RAS may be a new way of treating ALI/ARDS.