Effects Of Metformin On Expression Of ATF6 And Caspase12 In Hippocampus Of Type 2 Diabetic Rats

Objective Investigate the effect of metformin on the expression of ATF6 and Caspase12 in the hippocampus of type 2 diabetic ratsMethod 1 Chose SPF 13-week-old male GK rats and Wistar male rats as experimental subject.Divided the male GK rat with random blood glucose ?11.1 mmol/L into model group(n=12)and metformin group(n=13)and Wistar male rats as the normal group(n=10).After two weeks of acclimatization,the metfromin group was given metformin(85mg/kg/d)for gavage for eight weeks and the model and normal groups were given equal dose of isotonic saline.the whole course,two rats in the model group and three in the metformin group died.2 After eight weeks,measured weight and FBG.3 observed the morphology of HE-stained cells in hippocampal CA1 region.4 Observed the expression of ATF6 and Caspase12 in the hippocampus by immunohistochemistry and Western blot respectively.All data were analyzed by SPSS 20.0 software,and were tested by ANOVA.Multiple comparison using LSD t test,P ? 0.05 was considered statistically significant.Result 1 After eight weeks,the status of weight and FBG in rats: compared with the normal group,the weight of the model group and metformin group was lower,the difference was statistically significant(P<0.05);but there was no significant difference in weight between the model group and metformin group(P>0.05).Compared with the normal group,the FBG in the model group and metformin group was higher,the difference was statistically significant(P<0.05);the FBG in the model group was significantly higher than that in the metformin group,the difference was statistically significant(P<0.05).2 HE staining results: In the normal group,the normal morphological neurons in the hippocampal CA1 area were numerous with orderly arrangement,complete cell membrane,clear nuclei,large round cells and homogeneous cytoplasm.In the model group,the normal nerve cells were the least,the arrangement was disorderly,and the nuclear pyknosis and nuclear rupture were obvious.Compared with the model group,the metformin group had a regular arrangement of nerve cells,and the number of neuron-deficient and degenerating cells was reduced.Compared with the normal group,the survival neurons in the hippocampal CA1 region were significantly decreased in the model group and metformin group,and the difference was statistically significant(P<0.05);Compared with the model group,the survival neurons in the hippocampal CA1 region were significantly increased in the metformin group,the difference was statistically significant(P<0.05).3 Immunohistochemical test results: the positive of ATF6 and Caspase12 proteins was cytoplasm with brown-yellow granules and different staining depths,mainly located in the cytoplasm.Compared with the normal group,the relative content of ATF6 protein in the model group and metformin group increased significantly,and the difference was statistically significant(P<0.05);Compared with the model group,the relative content of ATF6 protein in the metformin group was reduced,the difference was statistically significant(P<0.05).Compared with the normal group,the relative content of Caspase12 protein in the model group and metformin group was significantly increased,and the difference was statistically significant(P<0.05);Compared with the model group,the relative content of Caspase12 protein in the metformin group was significantly reduced,and the difference was statistically significant(P<0.05).4 Western blot results : compared with the normal group,the expression of ATF6 protein in model group and metformin group increased significantly,the difference was statistically significant(P<0.05);Compared with the model group,the expression of ATF6 protein in the metformin group was significantly reduced,the difference was statistically significant(P< 0.05).Compared with the normal group,the expression of Caspase12 protein in the model group and metformin group was significantly increased,and the difference was statistically significant(P<0.05);Compared with the model group,the expression of Caspase12 protein in the metformin group was significantly reduced,and the difference was statistically significant(P<0.05).Conclusion 1 There may be ERS and its induced apoptosis in the hippocampus of T2 DM rats.2 Metformin can improve fasting blood glucose and weight in T2 DM rats.3 Metformin can reduce the expression of ATF6 and Caspase12 in hippocampal CA1 regionin the hippocampus CA1 region of T2 DM rats.4 Metformin prabably has anti-ERS effect,which can reduce hippocampal neuronal damage and protect cognitive function.