Mechanisms Of Survivin In The Inhibition Of The Apoptosis Induced By Radiation In IEC-6 Cells

After severe trauma, radiation is not only a common pathological process of various types of intestinal diseases, but also a vital initiative factor in the other viscera speculum dysfunction induced by intestines. The mechanisms of apoptosis induced by radiation gradually come to be one of the highlights in life science. Apoptosis or necrosis of intestine epithelial cells is a feature of the intestinal diseases process that contributes to progressive decline in the other viscera speculum dysfunction and intestines failure induced by radiation. It will be of important themry and practical significance that to evaluate the possible mechanisms of intestines damage induced by radiation, and to reveal the operative methods of that to resist intestines damage induced by radiation.Recent studies showed the apoptosis is a major style of cell death induced by radiation. Programmed cell death plays critical roles in a wide variation of physiological processes during the fetal development and the formation of immune system,while the super-apoptosis is the mechanisms of body damage induced by the harmful environments' factor(radiation, hypoxia et al). Survivin is a member of the inhibitor of apoptosis (IAP) gene family that exhibits differential expression in nearly all human cancers but not in most normal tissues. It has the effects on inhibiting cell apoptosis and promoting cell proliferation. Some members of the inhibitors of apoptosis protein (IAPs) family(Suvivin et al) block apoptosis by binding and neutralizing pro-apoptotic Caspase-3, -7, -9/6 and Cyt c, but the mechanisms of Survivin in the inhibition of the apoptosis induced by radiation is still obscure now.In this study, we treated the radiosensitive IEC-6 cell line, , which derived from rat jejunum epithelium cells, with the condition of 37℃, 2% O₂ mixture for 8h and reoxygen for 48h as hypoxia preconditioning model. After irradiated by 35Gy ⁶⁰Co γ ray, the cells were detected the apoptosis rate and proliferation, and were examined by flowcytometry,agarose gel electrophoresis and Western blotting to explore the mechanisms of Survivin in the apoptosis induced by radiation. Main results were described as following.1. With the condition of 37°C, 2% O2mixture for 6^ 8^ lOh and reoxygen for 2^ 48h as hypoxia preconditioning model, induced the expression of surviving. And it got the best result in the hypoxia 8h/ reoxygen 48h group.2. Compared with the control group, the apoptosis rate of the simple radiation group with the 35Gy Co y ray obviously increased, which is characterized by induction of genomic DNA fragmentation, and appearance of apoptotic morphological features, the Caspase-9/^ -3 activity of the simple radiation group with the 35Gy 60Covray plus obviously increased. With the condition to inhibit Caspase-3, the apoptosis rate and Caspase-3 activity in the simple radiation group obviously decreased.3. Compared with simple radiation group, the apoptosis rate and Caspase-9/6> -3 activity of the hypoxia / reoxygen group obviously decreased, but it was still higher than the control group. With the condition of to inhibite survivin, the apoptosis rate^ Caspase-3 activity the hypoxia / reoxygen group obviously increased. Caspase-9/6 activity happen on variation.Based on all the results, the conclusion is: the apoptosis is a major style of cell death induced by radiation in IEC-6 cells, the key point is the enhancement of Caspase-3 activity. Hypoxia preconditioning (HPC) could induce the expression of survivin in IEC-6 cells and survivin could decrease the apoptosis rate and DNA damage induced by radiation, survivin could decrease the Caspase-3 activity, inhibit the apoptosis induced by radiation.