The Experiment Study On The Protective Effect Of Limb Remote Ischemic Preconditioning And Its Mechanism Against Lung Ischemic Reperfusion Injury In Rabbits

Objectiv:To study the protective effect of limb remote preconditioning (RPC) against lung ischemia reperfusion injury and to discuss mechanism against lung ischemic reperfusion injury in rabbits. Methods Eighteen healthy rabbits, weighing 2.0～2.5 kg, were randomly divided into three groups:sham operation group (S), ischemic reperfusion group (I/R) and limb remote ischemic preconditioning group (R), six rabbits in each group. The left hilum of lung was threaded but no occlusion was performed, then the animals were observed for 330 min in S group; Left lung ischemic reperfusion was produced by left hilum of lung occluded for 60 min followed 180 min reperfusion in I/R group. Limb remote ischemia was induced by placing tourniquet on both legs, The animals underwent 3 episodes 10 min leg ischemia at 10 min intervals, then left hilum of lung was occluded for 60 min followed 180 min reperfusion in R group. Blood samples from left interal carotid artery were taken for blood gas analysis after catheter was placed into left interal carotid artery and at 15,30,60,120, 180 min after reperfusion, respectively. The plasma IL-6, TNF-αand IL-10 concentrations were measured afer catheter was placed into left interal carotid artery and at 60,120,180 min after reperfusion respectively. Respiratory index (RI) was calculated. The animals were killed at 180 min of reperfusion and the left lungs were removed for determination of SOD and MPO activity, MDA content, expression of P-selectin, calculation of W/D lung weight ratio, lung permeability index(LPI) in bronchoalvelar laveolar lavage fluid(BALF) and histological examination with light microscrope. Diffuse alveolar damage (DAD) scores was estimated. Results: Compared with S group, RI, MDA content, MPO activity, W/D lung weight ratio, LPI in BALF, expression of P-selectin, DAD scores, the plasma concentration of IL-6 and TNF-a were significantly increased while SOD activity and the plasma IL-10 concentration decreased in I/R group (P<0.05 or 0.01). Compared with I/R group, RI, MDA content, MPO activity, W/D lung weight ratio, LPI in BALF, expression of P-selectin, DAD scores, the plasma concentration of IL-6 and TNF-a were significantly decreased while SOD activity and the plasma IL-10 concentration increased in R group (P<0.05 or 0.01). There were no significant differences in the indices mentioned above between group R and S(P>0.05). The histological morphologic damages in S and R group were significantly milder than in I/R group. Conclusion:Limb remote preconditioning upregulate activities of antioxidant enzymes, then scavenge the free radicals produced during ischemic reperfusion, decrease pulmonary capillary ability, pretect the lung tissue from lung ischemic reperfusion injury. Limb remote preconditioning may also inhibit the expression of IL-6, TNF-α, P-selectin, and increase the expression of IL-10,so as to play a role in lung protection by balancing the anti-inflammatory and inflammatory reaction of immune function.