Mechanism Of Energy Metabolism In Hippocampus Of Rats With Cognitive Impairment Induced By Diabetes Mellitus

With the continuous development of society,diabetes has gradually become one of the major diseases that threaten human health and even cause death in an environment of rising living standards.Diabetic patients have a relatively long course of disease and are often accompanied by complications of different organs such as the brain,feet and eyes.Among them,the process of brain complication of diabetic patients is mainly mild cognitive impairment,and later stage of development is cognitive impairment and even leads to dementia.Therefore,the study of diabetic encephalopathy has become the focus of experts at home and abroad in recent years.It is well known that the uptake of glucose and other nutritive substances in the body of diabetic patients is different from that of normal people,and the energy metabolism process also changes significantly.This topic as long as it is based on the cognitive impairment of diabetes rats hippocampal tissue related mechanism to detect energy metabolism process,validation of diabetic cognitive impairment and hippocampus energy metabolism process of functional change are essential.Objective:Through the key enzyme activity in the process of energy metabolism level,main metabolites in key metabolic product in the process of the metabolism and transport protein expression,to study the diabetes rats to cognitive impairment and the changes of energy metabolism of rat hippocampal tissue cells.Methods:1.The male Wistar rats were randomly divided into control group and diabetes model group.By intraperitoneal injection of model group chain urea with cephalosporins(STZ)duplicate the diabetes model,in the model 80d with Morris water maze test diabetic rats learning and memory ability,cognitive impairment to diabetes rats filtered for subsequent experiments.2.using enzyme-linked immunoassay(ELISA)process of energy metabolism in the rat hippocampus key enzyme hexokinase(HK),pyruvate kinase(PK)and mark in the Krebs cycle enzyme succinate dehydrogenase(SDH)energy level for testing.3.Enzyme linked immunoassay(ELISA)was used to detect the ATP content of pyruvate,lactic acid and energy metabolism of the main metabolites in rat hippocampal tissue.4.Western-blot analysis was used to analyze the expression levels of glucose transport-4(GLUT-4),hypoxia-inducible factor-1?(HIF-1?)and single-carboxyl transport-4(MCT-4)in rat hippocampal tissue.Results:After intraperitoneal injection of STZ 72h,63 rats were formed,with a rate of 77.8%.After the model was established for 75d,the number of rats with diabetic cognitive impairment after the screening of water maze was 5.1.through the cognitive impairment in the control group,diabetes group and diabetes group of key enzymes in rat hippocampus and signature of the enzyme activity detection is found between groups:compared with control group,diabetes group HK energy levels,there is significant difference(P<0.05),PK vitality and SDH activity levels also increased obviously,there is a very significant difference(P<0.01);Compared with the control group,the activity level of HK,PK and SDH in diabetic cognitive impairment group increased,but there was no significant change(P<0.05).However,compared with the diabetes group,the level of HK activity in the diabetic cognitive impairment group decreased,with no significant change(P>0.05),but the activity level of PK and SDH decreased and there was a significant difference(P<0.05).2.through the cognitive impairment in the control group,diabetes group and diabetes group related metabolites in rat hippocampus content detection is found between groups:compared with control group,diabetes group of pyruvic acid,lactic acid content in the hippocampus and ATP content were no significant difference(P>0.05),Compared with the control group,the content of pyruvate and ATP in the diabetic cognitive impairment group showed a decreasing trend,with significant difference(P<0.05),but there was no significant difference in lactic acid content(P>0.05).Compared with diabetes group,the content of pyruvate,lactic acid content and ATP content of diabetes mellitus were also decreased,with no significant difference(P>0.05).3.The results of Western-blot test showed that the expression of GLUT-4 in the hippocampal tissues of diabetic group and diabetic group was significantly decreased compared with the control group(P<0.05).However,there was no significant difference in the expression of GLUT-4 in the hippocampal tissues of the diabetic group compared with the diabetes group(P>0.05).Group compared with control group,diabetic rats hippocampal tissues MCT-4 expression of significant increases(P<0.05),the expression of MCT-4 in diabetic cognitive dysfunction group decreased but there was no significant difference(P>0.05);Compared with diabetes group,there was no significant difference in MCT-4 expression in the hippocampal tissue of diabetic cognitive disorder group(P>0.05).There was no significant difference in the expression of HIF-1? in the hippocampal tissue of the control group and diabetes group and diabetic cognitive impairment group(P>0.05).Conclusion:Diabetes and diabetic cognitive dysfunction group of glucose uptake capacity decreases,but the diabetes mellitus model of rat hippocampal cells in glycolysis hexokinase,pyruvate kinase and succinate dehydrogenase activity in the Krebs cycle,metabolite pyruvic acid,lactic acid and ATP did not increase,compensatory enhance the enzyme activity show that hippocampal tissue cells,regulates energy metabolism,still can meet cells demand for energy to maintain the normal physiological function.Compared with diabetes group,diabetic cognitive dysfunction group hippocampal tissue cells corresponding glycolysis and enzyme activity of the Krebs cycle significantly,pyruvic acid and ATP content decreases,the hippocampus tissue due to reduced productivity,causing cell physiological function changes,causing cognitive dysfunction.It is speculated that when the diabetes develops to a certain stage,due to the influence of energy metabolism,the energy generation is insufficient and the physiological function of the hippocampal cells changes,leading to the development of cognitive dysfunction of diabetes.