The interventive effects and mechanisms of erythropoietin postconditioning on celluar apoptosis of lung ischemia/reperfusion injury in rats

Abstract

Abstract: AIM: To investigate the interventive effects and mechanisms of erythropoietin postconditioning on celluar apoptosis of lung ischemia/reperfusion injury in rats. METHODS: Adult male Sprague-Dawley rats were randomly divided into 5 groups based upon the intervention (n=8): control group (group C), lung ischemia reperfusion group (group I/R), I/R+EPO(group EPO), EPO+solvent control 1(0.4%DMSO of the PBS solution)(group D), EPO+U0126(group U). At the end of the experiment, the wet to dry wight ratio(W/D) of the lung tissue was tested; the pneumocyte apoptosis index(AI) was achieved by terminal deoxynucleotidyl transferase mediated dUTP nick end abeling(TUNEL) ; the content of Bcl-2 and Bax in cytoplasm was determined with immunohistochemistry, Bcl-2 mRNA and Bax mRNA in lung tissues were determined by RT-PCR. The pathological changes of lung tissue were observed under light microscope and the index of quantitative assessment(IQA) of histologic lung injury was counted by HE staining. RESULTS: Compared with group C, W/D, IQA and AI of lung tissue were increased in group I/R, the expression of Bcl-2 protein and Bcl-2 mRNA were decreased, the expression of Bax protein and Bax mRNA were increased, the ratio of Bcl-2/Bax was decreased.There were abnormal morphological changes under the light microscope; compared with group I/R, W/D, IQA and AI of lung were decreased in EPO, D and U groups, the expression of Bcl-2 protein and Bcl-2 mRNA were increased but the Bax protein and Bax mRNA were decreased, the ratio of Bcl-2/Bax was increased. The morphological changes under the light microscope markedly reversed in EPO, D and U groups;there was no statistical difference between group D and group EPO; compared with group EPO, W/D, IQA and AI of lung were increased in group U, the expression of Bcl-2 protein and Bcl-2 mRNA were decreased, the expression of Bax protein and Bax mRNA were increased, the ratio of Bcl-2/Bax was decreased. There were abnormal morphological changes under the light microscope in group U than group EPO. CONCLUSION: Erythropoietin postconditioning may attenuate pneumocyte apoptosis in LIRI by activating ERK1/2 signal transduction pathway, and up-regulating expression of Bcl-2/ Bax ratio.

Key words: erythropoietin, postconditioning, reperfusion injury, lung, apoptosis

CLC Number:

R965.2

JIN Xiao-sheng, WU Li-feng, QIAN Xiao-ying, SHAO Mei-qin, WANG Wan-tie. The interventive effects and mechanisms of erythropoietin postconditioning on celluar apoptosis of lung ischemia/reperfusion injury in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(4): 371-376.

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