The mechanism of protection against myocardial oxidative stress injury by anovel lymphotoxinbinding p55TNFRselectively

doi:10.3969/j.issn.1002-1949.2015.10.015

Abstract：Objective To investigate the effect of a novel lymphotoxin with selectively binding to p55 tumor necrosis factor receptor (p55TNFR) on myocardial oxidative stress injury , and explore the mechanism.Methods Primary cardiomyocytes were prepared from hearts of neonatalWistar rats , and myocardial oxidative stress injury model was established by hydrogen peroxide ( H2 O2 ) .Then cells were divided into normal group , H2 O2 treatment group, and treatment groups with rhLTαor rhLTα-Q107E. Cell apoptosis was detected by flow cytometry , and the activation of NF -κB was detected by Western blot analysis .Real -time quantitative RT -PCR assay was applied to detect the expression levels of anti-apoptotic molecules (Bcl-2, Bcl-X and XIAP).The expression and activities of MnSOD or CuZn-SOD were detected by Western blot or WST .Results Increased cell apoptosis and the activity of Caspase-3 was observed in the oxidative stress injury model of myocardial cells .The expression of anti-apoptotic protein Bcl -2, Bcl-xL and XIAP were decreased .The expression level and activity of MnSOD were decreased .However , the treatment of rhLTα-Q107 E, but not wild type LTα, reversed these changes , along with the activation of NF -κB.Conclusion This work demonstrates that rhLTα-Q107 E plays a role on the protection against myocardial oxidative stress injury , through the activation of NF-κB, up -regulating the expression of the anti -apoptotic molecules , activating mitochondrial MnSOD, which was better than the wild type LTα.