Protective Effect Of Curcumin On Mitochondria Of Pancreatic Exocrine Cells And Regulation Of Energy Metabolism After Radiation Injury

Purpose: To elucidate the stress response and energy metabolism of pancreatic exocrine cells induced by ionizing radiation,and to explore the role of curcumin in pancreatic exocrine cell radiation injury and its mechanism.Methods: Rat pancreatic exocrine cells(AR42J)were divided into experimental group and control group.The two groups were divided into three subgroups,which were treated with 0,4,and 8?M curcumin.The experimental group to accept a one-time high-dose X-ray irradiation(6Gy),simulated acute radiation damage events.The expression of stress and energy metabolism related factors,LDHA,PDH and HIF-1? were detected by Wensten-blot.The cell viability was detected by MTT assay.Fluorescence detection of cell ATP and ROS production.The experimental results were further validated by in vivo experiments.The cell culture medium was collected to detect the lactic acid content.The expression of HIF-1? was silenced by siRNA technique,and then the expression of LDHA and PDH and the lactic acid content in the medium were detected again.24 Wistar rats were randomly divided into 4 groups(labeled as group A: control group,group B: simple drug-added group,group C: simple irradiation group,group D: irradiation + drug-added group),6 rats in each group.The rats in groups B and D were intraperitoneally injected with curcumin(200 mg/kg)on the first day.The rats in each group were given 12 Gy X-ray irradiation or sham irradiation on the second day.On the third day,all rats in the group were sacrificed.The pancreas was dissected and examined the expression of HIF-1?,LDHA and PDH by Wensten-blot.Results: We demonstrate:1)Compared with the control group,the decrease of mitochondrial membrane potential(??m)was noticed which indicate mitochondria damage.2)The expression of HIF-1? was significantly increased by irradiation,and LDHA,the key factor of glycolysis was significantly increased and PDH expression was down-regulated.3)MTT assay showed a decrease in cell proliferation and the production of ROS was increased by microplate reader.4)Silence HIF-1? by siRNA technologyto have eliminates irradiation-induced energy metabolism transformation partly.In the experimental group,the increased expression of HIF-1? and LDHA was reversed by curcumin treatment,PDH was partially restored,the free radical scavenging was effectively removed,and the proliferation of cells and the ATP production were rised.5)The animal experiments have got the same result.Conclusions:After exocrine radiation damage,pancreatic exocrine cells undergo oxidative stress and mitochondria are damaged.Ionizing radiation enhances the energy metabolism of cells by up-regulating the expression of HIF-1?,and the glycolytic pathway is strengthened,while the aerobic oxidation of mitochondria is inhibited.Curcumin exerts its protective effect on pancreatic exocrine cells by the following pathways: 1.Down-regulating HIF-1? expression,correcting radiation-induced pancreatic exocrine cell energy metabolism disorder,2.Antioxidant,protecting cell mitochondria.