The Mechanism Research Of Energy Dysmetabolism Of Spleen Asthenic Syndrome Based On Mitochondrial Oxidative Damage And Repair

ObjectiveMitochondrial disfunction related myasthenia gravis spleen asthenic patients,spleen asthenic rat models were regarded as study objects in this study.To investigate the expression of mitochondrial OGG1、NTH1、MPG mRNA in clinical part and the level of mitochondrial SOD、GSH-Px、MDA of skeletal muscle in spleen asthenic rats.Try to explore the pathogenesis of spleen asthenic from the point of mitochondrial energy metabolism and the disorder of energy metabolism’ s pathogenesis of spleen asthenic from free radical.Use strengthening spleen and invigorating Qi medicine to intervene.Provide an objective scientific basis for further elucidate the mechanism of the invigorating Qi medicine.MethodsClinical specimens of Case studies from April 2012 to July 2013 at th e First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine Spleen inpatient cases of the disease were collected spleen asthenic patients with myasthenia gravis IIb 16,and in the school division health volunteers recruited eight healthy volunteers.Someone asked each subject’s general information,and extracted each subject’s fasting peripheral venous blood 3.5ml,used PCR method to detect the mRNA expression of mitochondrial OGG1、NTH1、MPG.42 SD.SPF rats were randomly divided into two groups,namely,the normal group 10,model group 32.The rats in model group were given abdominal subcutaneous injection of reserpine 0.5mg/kg/d,while the rats in normal group were given equal quantity normal saline for 8 days.Recorded the general condition of rats,D-xylose urine excretion rate in order to determine whether the spleen asthenic rat model was successfully established.Model group appeared to reduce food intake,significant weight loss,like get together,loose stool and D-xylose excretion rate decreased other changes,proved successful modeling.Using a random number table,randomly selected 7 normal rats and 14 rats in model group.The successful model rats were randomly divided into Si jun zi decoction group and spleen asthenic group,each group 7.Treatment group were given si jun zi decoction,as well as spleen asthenic group and normal group were given normal saline.To measure Urea D-xylose excretion rate after 3 weeks and evaluate condition of spleen asthenic rats’by Urea D-xylose excretion rate.After 3 weeks of the treatment,investigated D-xylose urine excretion rate and extracted mitochondria from skeletal muscle cells to investigate the level of mitochondrial SOD、GSH-Px、MDA,observed Si jun zi decoction action on these indicators.Results1.Spleen asthenic group with gene expression of deletion of mtDNA/Wild type mtDNA had higher proportion than normal group(p<0.01).2.The expression of mRNA OGG1 in spleen asthenic group was higher than normal group(p<0.05),the expression of mRNA NTH1、MPG was high,which had a significant difference compared with normal group(p<0.01).3.After the injection,there was a significant difference between normal group and model group in body weight(p<0.01).However,Si jun zi decoction group body weight was still lower than normal group(p<0.01).After 3 weeks by mouth,urinary D-xylose excretory rate in Si jun zi decoction group was recovered(P>0.05),there was an upward trend in body weight between Si jun zi decoction group and spleen asthenic group,the two groups showed no significant difference(P>0.05).But there was a significant difference between normal group and spleen asthenic group(P<0.01).4.Compared with normal group,the level of SOD、GSH-Px was decreased and the level of MDA was increased in skeletal muscle of spleen asthenic rats(p<0.05).Compared with spleen asthenic group,Si jun zi decoction group enhance the level of SOD、GSH-Px and decrease the level of MDA(p<0.05).Conclusion1.Myasthenia gravis spleen asthenic patients showed mtDNA deletion,resulting in oxidative phosphorylation respiratory chain dysfuntion,ultimately causing cell energy metabolism;The expression of mRNA OGG1、NTH1、MPG is high in spleen asthenic group,which has a significant difference compared with normal group.Mechanism may be mitochondrial damage in spleen asthenic which causes mitochondrial DNA repair itself.So three glycosylation enzymes are highly expressed.2.The reserpine induced spleen asthenic requires spleen asthenic rat model by observing general condition、urinary D-xylose excretory rate.In mitochondrial oxidative damage,by detecting the oxidation,antioxidant-related indicators,founded spleen asthenic rats’ skeletal muscle mitochondrial SOD、GSH-Px activity decreased,MDA content increased.So spleen asthenic is closely related with the oxidative damage of mitochondria.Si jun zi decoction used spleen asthenic rat model for therapeutic intervention,it improves level of spleen asthenic model rats skeletal muscle mitochondrial SOD、GSH-Px and reduces the level of MDA,suggesting Si jun zi decoction can improve the body’s antioxidant capacity,reduce lipid peroxidation products,and thus reduce the mitochondrial oxidative damage,regulate the body’s energy metabolism.