Abstract: AIM: To investigate the effects of metallothionein induced by ZnSO₄ on pneumocyte apoptosis after lung ischemia/reperfusion injury in rats. METHODS: Adult male Sprague-Dawley rats were randomly divided into 3 groups based upon the intervention (n=8): control group (C), LIR group (I/R), LIR+ ZnSO₄ group (M). At the end of the experiment, the content of metallothionein was tested in lung tissue; blood specimens drawn from the arteria carotis were tested for the content of Malondialdehyde (MDA), the activity of Superoxide dismutase (SOD) and Myeloperoxidase (MPO); the pneumocyte apoptosis index (AI) was achieved by terminal deoxynucleotidyl transferase mediated dUTP nick end abeling (TUNEL); the expression of Bcl-2, Bax protein in lung tissue were accessed by quantitative immunohistochemistry (IHC) and Bcl-2, Bax mRNA by RT-PCR; ultrastructural changes of lung tissue were ob- served by transmission electron microscope. RESULTS: Metallothionein induced by ZnSO₄ could significantly attenuate the MDA level, MPO activity and improve SOD activity in blood serum which was comparable to I/R and significantly reduced the number of TUNEL-positive cells vs. the I/R group, expressed as AI (% total nuclei) from 39.03±3.46 to 15.50±1.02 (P<0.01). The protein and mRNA expression of Bcl-2, Bax showed that metallothionein significantly attenuated the ischemia/ reperfusion-upregulated expression of Bax protein but improved the expression of Bcl-2 that improved the Bcl-2/ Bax ratio(P<0.05 or P <0.01). There were abnormal changes of the ultrastructure in I/R, and markedly reversed in MT group. CONCLUSION: Metallothionein induced by ZnSO₄ may attenuate pneumocyte apoptosis in LIRI by up-regulating expression of Bcl-2/ Bax ratio and by inhibiting oxidant generation, neutrophils filtration.

Key words: Lung, Ischemia/reperfusion injury, Metallothionein, ZnSO₄, Apoptosis