Abstract:

Objective   To investigate the relationship between oxidative stress and apoptosis in lung ischemia/reperfusion injury, and to observe the inhibitory effects of human Thioredoxin in lung ischemia/reperfusion injury. Methods   Single lung in situ ischemia/reperfusion animal model was used. Eighty four Wistar rats were randomly divided into control group, ischemia / reperfusion  group and human Thioredoxin group. Lung tissue was taken to measure the ratio of wet to dry lung tissue weight (W/D）, index of quantitative assessment of histologic lung injury (IQA), activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA). Terminal deoxynucleotidyl transferase dUTP nick end labeling and immunocytochemistry techniques were used to observe the pneumocyte apoptosis index (AI) and apoptosis signal-regulating kinase 1 (ASK1) expression in various phases of lung ischemia/reperfusion. Results   The activity of SOD showed a time-dependent decrease in the ischemia / reperfusion  group (P<0.01), while the content of MDA, values of W/D, IQA and AI , and expression of ASK1 were gradually increased with the time of reperfusion prolonging in lung tissues of lung ischemia/ reperfusion injury compared with the control group (all P<0.01). The hTrx suppressed apoptosis as well as expression of ASK1 and the contents of MDA， W/D and IQA (P<0.01). There was a negative correlation between AI and SOD (r=-0.820, P<0.01). There were significant correlations between W/D, IQA, MDA, ASK1 protein, and AI (r=0.721, 0.835, 0.844, 0.675, respectively; all P<0.01). ASK1 protein was negatively correlated with SOD activity (r=-0.749, P<0.01), and positively correlated with MDA content (r=0.721, P<0.01). Conclusions   Activation of ASK1 and its initiation on cell apoptosis of lung tissues and oxidative stress may contribute to the pathogenesis of lung ischemia/reperfusion injury. The protective effects of hTrx include suppressing lipoperoxide reaction and down-regulating the expression of ASK1 and blocking apoptosis in lung tissues of lung ischemia/reperfusion injury.

Key words: Lung; Reperfusion injury; Apoptosis;  Thioredoxin; Apoptosis signalregulating kinase1