The Effect Of Aerobic Pathway In Glucose Metabolism On Parkinson's Disease

Objective: To explore the difference of aerobic pathway in glucose metabolism in Parkinson's disease(PD)mice model and clinical patients,which will provide a new target for diagnosis and treatment of Parkinson's disease.Methods: Twenty male C57BL/6 mice were randomly divided into two groups of 10: A.Control group(peritoneal injection of saline for 7 days);B.PD model group(peritoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 7 days).Blood samples of 10 Parkinson's disease patients and 10 normal volunteers were collected,and the brain tissues of mice after successful modeling were taken.After the RNA was extracted from the above tissues,the expression of key enzymes in the aerobic pathway of glucose metabolism was compared by PCR.The central carbon metabolism experiment was compared with the intermediate products in the aerobic pathway of glucose metabolism,and the values were recorded and statistically analyzed.Results: In a mouse model,compared to the control,the expression of hexokinase 2(HK2),6-phosphofructokinase1(PFK 1),?-ketoglutarate dehydrogenase complex(OGDH),citrate synthase(CS)on mRNA levels Increased in PD mice,and there were statistical differences(P <0.05 in the difference in expression of HK2 and CS,P <0.01 in the expression of PFK1 and OGDH),the metabolites glucose 6-phosphate(G6P),fructose-6-phosphate(F6P),pyruvate,and 2-Ketoglutaric acid(2KGA)were significantly reduced in mice in the PD group.3-phosphoglycerate(G3P)was higher than the control group,and glucose metabolism was inhibited in the PD model;it was found in clinical patients that the expression of HK2 in PD patients were reduced on mRNA levels compared with the control group,and CS was increased(P <0.05).Glucose 6-phosphate(G6P),fructose-6-phosphate(F6P),pyruvate,2-Ketoglutaric acid(2KGA),succinic acid,fumarate and maleic acid were significantly higher than those in control group.glycolysis was more active and glucose aerobic metabolism was inhibited in PD patients.Conclusion: In PD mice model,we found that glucose metabolites like glycolysis and tricarboxylic acid cycle are reduced in brain tissue,and the expression of enzyme increased,and glucose metabolism is inhibited in the overall brain tissue.The overall rate of glucose metabolism in brain tissue is low,the power is failure,the key enzyme changes in metabolic like HK2,PFK1,OGDH and CS.The overall glucose metabolic product is cumulative.In PD patient's tissue,the expression of key enzyme HK2 and PFK1 were reduced,CS has higher expression.Glycolysis was more active than that in healthy person,and glucose aerobic metabolism was inhibited in PD patients.In short,glycolysis and the Krebs cycle in Parkinson's disease are mainly changed in HK2,CS.