Effect of therapeutic hypercapnia preconditioning on lung ischemia-reperfusion injury in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of therapeutic hypercapnia preconditioning on lung ischemia-reperfusion (I/R) injury in rats.Methods Forty healthy adult Sprague-Dawley rats of either sex,aged 2 months,weighing 250-300 g,were divided into 5 groups (n=8 each) using a random number tablesham operation group (group S),grouP I/R and preconditioning with therapeutic hypercapnia of different level groups (group THP1-3).Lung I/R injury was induced by clamping the left hilum of lung for 45 min followed by 120 min of reperfusion.In THP1-3 groups,the respiratory parameters were adjusted at 5 min of stability after isolating the left hilum of lung to make PETCO2 reach 55-65,65-75 and 75-85 mmHg respetively and maintained at this level for 5 min,normal ventilation was then used to make PETCO2 restore the normal level,continuously repeating for 3 circles,and then the left hilum of lung was blocked for 45 min followed by 120 min of reperfusion.The bronchoalveolar lavage fluid (BALF) was collected at the end of reperfusion for determination of the total protein (TP) concentration using Coomassie brilliant blue staining.Lung tissues were obtained at the end of reperfusion for examination of pathological changes after haematoxylin and eosin staining (under a light microscope) and for determination of wet/dry weight ratio (W/D ratio),malondialdehyde (MDA) content,superoxide dismutase (SOD) activity,interleukin-8 (IL-8) and IL-10 contents (by enzyme-linked immunosorbent assay),tumor necrosis factor-alpha (TNF-α) expression (by immunohistochemistry) and expression of TNF-α mRNA (by real-time polymerase chain reaction).Results Compared with group S,the TP concentration in BALF,W/D ratio and contents of MDA,IL-8 and IL-10 in lung tissues were significantly increased,the SOD activity was decreased,the expression of TNF-α mRNA was up-regulated (P＜0.05),strong positive expression of TNF-α was found,and the pathological changes of lung tissues were aggravated in group I/R.Compared with group I/R,the TP concentration in BALF,W/D ratio and contents of MDA and IL-8 in lung tissues were significantly decreased,the SOD activity was increased,the expression of TNF-α mRNA was down-regulated (P＜0.05),no significant change was found in IL-10 content (P＞0.05),the staining range and intensity of TNF-α were decreased,and the pathological changes of lung tissues were significantly attenuated in THP1-3 groups.Conclusion Therapeutic hypercapnia preconditioning can reduce lung I/R injury in rats,and the mechanism is related to inhibiting inflammatory responses and oxidative stress responses.