| [Objective]The study was to investigate the effect of proanthocyanidins on antioxidant activity,the content of divalent mineral,the number of neuron apoptosis,synaptosomes and neuronal apoptosis related gene expression in the brain of rats with iron overload,and to provide a theoretical basis for the functional development of proanthocyanidins.[Methods]In the test,40 healthy(200±5)g and(60±5)g male rats were randomly divided into four groups,and named as control group,iron overload group,proanthocyanidins group and test group.After 7 days of adaptive feeding,the rats of acute and chronic iron overload were established by intraperitoneal injection of iron dextran with every other day dose of 100 mg kg-1 and 2.5 mg kg-1 daily.The test group was also treated with every other day dose of 100 mg kg-1 and 2.5 mg kg-1 daily iron dextran.And the proanthocyanidins were intragastrically infused daily at doses of 100 mg kg-1 and25mg kg-1,respectively.The control group was given 0.9%physiological saline.The rats in acute test was fed 10 days and was fed 7 weeks in chronic test.After feeding,the hippocampus and cortex were collected.and the contents of iron,calcium,zinc,magnesium and copper in brain were measured by ICP-MS.The MDA,SOD,GSH-Px and CAT was determined by related kits.Apoptotic cells and synaptosomes were labeled with DNA end labeling and immunofluorescence indirect staining respectively,then we counted the number of apoptotic cells and synaptosomes in brain tissue.The expression of levels of Fas,Bax,Bcl-2.CREB and GLUT-1 were studied by real-time RT-PCR.[Results](1)Compared with the control group,the contents of iron and calcium increased significantly while the zinc and magnesium decreased significantly in the acute and chronic iron overload group(P<0.01).The content of iron in the proanthocyanidins group decreased significantly(P<0.05),the content of calcium decreased,but the difference was not significant.The content of zinc and magnesium was increased significantly(P<0.05,P<0.01).Compared with the iron overload group,the content of iron and calcium decreased significantly while the zinc and magnesium increased significantly in the test group(P<0.05,P<0.07).There were no significant changes in the copper content.(2)Compared with the control group,the content of MDA nincreased significantly(P<0.01),and the activity of SOD,GSH-Px and CAT decreased significantly in the iron overload group in the acute and chronic test(P<0.01).The content of MDA in the proanthocyanidins group significantly decreased(P<0.05),the activity of SOD and GSH-Px in the proanthocyanidins group significantly increased(P<0.01),the acute CAT activity increased,but the differences were not significant while the chronic CAT activity increased significantly in the proanthocyanidins group(P<0.05).Compared with the iron overload group,the content of MDA in the test group significantly decreased(P<0.05,P<0.01),the activity of SOD,GSH-Px and CAT increased significantly(P<0.05,P<0.01).(3)Compared with the control group,the number of TUNEL positive cells in the cortex and hippocampus of the rats in the iron overload group significantly increased,and the apoptosis of neurons was severe.There was no obvious apoptosis in the cortex and hippocampus neurons in the proanthocyanidins group of rats.Compared with the iron overload group,the number of TUNEL positive cells in the test group decreased and the apoptosis of neurons decreased compared with that of the iron overload group.The number of rat cortical and hippocampal synaptosomes in control group were maintained at a constant level,while there were no significant differences in the proanthocyanidins group.Compared with the iron overload group,the number of cortrol and hippocampal synaptosomes in the test group increased.(4)Compared with the control group,the expression of Fas and Bax in the cortex and hippocampus of the iron overload group significantly increased in the acute and chronic test(P<0.05,P<0.01).The expression of Bcl-2,CREB and GLUT-1 mRNA in cortex and hippocampus were significantly decreased(P<0.05,P<0.01),and the expression of chronic Bcl-2 gene was significantly decreased in the acute test(P<0.05,P<0.01).The expression of Fas and Bax mRNA in the cortex and hippocampus of the proanthocyanidins group decreased significantly in the acute test(P<0.05,P<0.01).The expression of Fas and Bax genes decreased,but the difference was not significant inchronic test(P<0.05,P<0.01).The expression of Bcl-2,CREB and GLUT-1 increased significantly,but the differences were not significant in chronic test.Compared with the iron overload group,the expression of Fas and Bax mRNA in the test group decreased significantly(P<0.05,P<0.07).The expression of BcI-2,CREB and GLUT-1 was significantly increased in acute test(P<0.05,P<0.01).The expression of BcI-2 was significantly increased in chronic test(P<0.05,P<0.01).[Conclusions]Proanthocyanidins could improve the brain function through regulating the mineral elements,the activity of antioxidant enzymes and cell apoptosis in brain with iron overload. |
