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Study On The Regulation Mechanism Of Electroacupuncture Pretreatment On Myocardial AMPK/PGC-1α Signal Transduction Pathway In Exhaustive Exercise Rats

Posted on:2020-08-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q ChenFull Text:PDF
GTID:1364330575455703Subject:Acupuncture and Massage
Abstract/Summary:PDF Full Text Request
ObjectiveUnder the guidance of the theory of acupuncture and moxibustion treatment of diseases in traditional Chinese medicine.Observing the experimental indexes of electroacupuncture pretreatment intervention on myocardial injury induced by exhaustive exercise in rats,such as exhaustive exercise time,left ventricular function,blood biochemical indexes of cardiac injury,mitochondrial structure and function,oxidative stress injury,expression of related factor proteins and genes in mitochondrial biosynthesis related signal transduction pathway.Taking AMPK as a breakthrough point,the effect of AMPK/PGC-1α on mitochondrial biosynthesis was studied to explore the mechanism of electroacupuncture preconditioning intervention on cardiac protection under exhaustive exercise in rats.In order to provide a new theoretical discussion and experimental basis for the early prevention and treatment of myocardial injury induced by exhaustive exercise and the reduction of exercise-induced body injury,we hope to provide a new theoretical discussion and experimental basis for the early prevention and treatment of myocardial injury induced by exhaustive exercise.MethodsSixty male SD rats were randomly divided into no-treatment control group,exhaustive exercise group,electroacupuncture pretreatment group,AICAR group,electroacupuncture preconditioning+Compound C group and Compound C group.Every day of the 14 days before exhaustive exercise,rats in no一treatment control group were mtraperitoneally injected with normal saline,in exhaustive exercise group were mtraperitoneally injected with normal saline and clenched for 15 minutes,in electroacupuncture preconditioning group and in electroacupuncture preconditioning+Compound C group were given electroacupuncture intervention of Zusanli,Guanyuan and Neiguan,in AICAR group were mtraperitoneally injected with AMPK agonist AICAR,in Compound C group gripped and stimulated for 15 minutes.On the day of the modeling,Electroacupuncture preconditioning+Compound C group and Compound C group were injected intraperitoneally with Compound C before modeling.Direct detection and sampling of rats in no-treatment control group.The other five groups of rats were swimming exhaustive exercise,and then the samples were detected.The length of exhaustive exercise,left ventricular function,serum CK-MB,LDH,cTnT,IL-6,IL-1β,myocardial TNF-α,MDA,SOD,GSH-Px,ATP,mitochondrial structure and respiratory function were recorded.AMPK/PGC-1 a signal was transferred to the expression of AMPK,PGC-1α,NRF1,NRF2,mtTFA protein and gene in the myocardium of the conduction pathway.ResultThe main results were as follows:1.the length of exhaustive exercise in electroacupuncture pretreatment group was higher than that in exhaustive exercise group and Compound C group(P<0.01),and the length of exhaustive exercise time in electroacupuncture pretreatment+ Compound C group was higher than that in Compound C group(P<0.01).The length of exercise time in electroacupuncture preconditioning group was lower than that in AICAR group(P>0.05).2.LVSP and LVEDP in exhaustive exercise group were lower than those in blank control group,and+LVdP/dtmax were lower than those in blank control group(P<0.01).The levels of LVSP and LVEDP in electroacupuncture pretreatment group were lower than those in blank control group(P<0 05),and those in exhaustive exercise group were higher than those in exhaustive exercise group(P<0 01).The levels of+LVdP/dtmax and+LVdP/dtmax in electroacupuncture pretreatment group were lower than those in blank control group(P<0 05).The levels of LVSP and LVEDP in electroacupuncture preconditioning+Compound C group were higher than those in Compound C group,LVSP,+LVdP/dtmax and+LVdP/dtmax in electroacupuncture preconditioning group were higher than those in AICAR group(P>0.05),and LVEDP in electroacupuncture preconditioning group was lower than that in AICAR group(P>0.05).3 The levels of serum LDH,CK-MB and cTnT in exhaustive exercise group were higher than those in blank control group(P<0.01).The levels of serum LDH,CK-MB and cTnT in electroacupuncture pretreatment group were lower than those in exhaustive exercise group(P<0.01),higher than those in blank control group and lower than those in AICAR group(P>0.05),and the serum levels in electroacupuncture preconditioning+Compound C group were lower than those in exhaustive exercise group(P<0.01).The levels of LDH,CK-MB and cTnT in Compound C group were lower than those in control group(P<0.05).4.The levels of serum IL一6 and IL-1β myocardial TNF-a in exhaustive exercise group were higher than those in blank control group(P<0.01).The levels of serum IL-6 and IL-1 β myocardial TNF-α in electroacupuncture preconditioning group were lower than those in exhaustive exercise group(P<0.01),higher than those in blank control group(P<0.01)and lower than those in AICAR group(P>0.05).Electroacupuncture preconditioning+Compound C group.The level of serum IL-1β was lower than that of Compound C group(P<0.01).5.The degree of myocardial morphological damage in exhaustive exercise group was more serious than that in blank control group,and the degree of myocardial morphological damage in electroacupuncture pretreatment group was more serious than that in blank control group,but lighter than that in exhaustive exercise group.The degree of myocardial morphological damage in electroacupuncture preconditioning+Compound C group was less than that in Compound C group,but there was no significant difference between electroacupuncture preconditioning group and AICAR group.6.The myocardial mitochondrial RCR and myocardial ATP in exhaustive exercise group were lower than those in blank control group(P<0.01).Myocardial mitochondrial RCR and myocardial ATP in electroacupuncture preconditioning group were higher than those in exhaustive exercise group(P<0.01),and those in electroacupuncture preconditioning group were lower than those in blank control group(P<0.05).Myocardial mitochondrial RCR was lower than that of AICAR group,ATP of myocardial tissue was higher than that of AICAR group(P>0.05),and ATP of myocardial tissue of electroacupuncture preconditioning+Compound C group was higher than that of Compound C group(P<0.05).7.The myocardial MDA in exhaustive exercise group was higher than that in blank control group(P<0.01),and the myocardial GSH-Px and T-SOD were lower than those in blank control group(P<0.01).The myocardial MDA in EA preconditioning group was higher than that in blank control group(P<0.01),lower than that in exhaustive exercise group(P<0.01)and lower than that in AfCAR group(P>0.05).The myocardial GSH-Px and T-SOD were lower in electroacupuncture preconditioning group than that in control group(P<0.01).It was higher in the blank control group(P<0.01),higher than that in the exhaustive exercise group(P<0.05)and higher than that in the AICAR group(P>0.05).The myocardial MDA in electroacupuncture preconditioning+Compound C group was lower than that in Compound C group(P<0.05),and the myocardial GSH-Px and T-SOD were higher than those in Compound C group(P<0.05).8.The gray ratio of myocardial AMPK,PGC-1α,NRF1,NRF2 and mtTFA protein in exhaustive exercise group was lower than that in blank control group(P<0.01).The gray ratio of myocardial AMPK,PGC-1α,NRF1,NRF2 and mtTFA protein in electroacupuncture preconditioning group was higher than that in exhaustive exercise group(P<0.01),but lower than that in blank group.The ratio of myocardial AMPK,PGC-1α,NRF1,NRF2 and mtTFA protein in acupuncture pretreatment+Compound C group was higher than that in Compound C group(P<0.01),which was higher than that in AICAR group(P<0.01),and was higher than that in Compound C group(P<0.01).9.the amplification multiples of AMPK mRNA,PGC-1 a mRNA,NRF1 mRNA,NRF2 mRNA and mtTFA mRNA in exhaustive exercise group were lower than those in blank control group(P<0.01).The amplification times of AMPK mRNA,PGC-1 a mRNA,NRF1 mRNA,NRF2 mRNA and mtTFA mRNA in electroacupuncture preconditioning group were higher than those in exhaustive exercise.The amplification times of AMPK mRNA,PGC-1 a mRNA,NRF1 mRNA,NRF2 mRNA and mtTFA mRNA in the acupuncture pretreatment+ Compound C group were higher than those in the Compound C group(P<0.01),which were lower than those in the blank control group(P<0.01)and higher than those in the AICAR group(P>0.05).ConclusionThe Conclusion of the paper were as follows:1.Exhaustive exercise caused injury to myocardial tissue,affected left ventricular function,increased the expression of myocardial injury markers in blood,and produced inflammatory reaction and oxidative stress injury to myocardium.Destruction of myocardial tissue structure and mitochondrial function.It is suggested that the injury of myocardial tissue caused by exhaustive exercise may be related to inflammatory reaction,oxidative stress injury and abnormal energy metabolism of mitochondria.2.Electroacupuncture pretreatment could prolong the time of exhaustive exercise in rats,and significantly down-regulate the expression of serum markers of myocardial injury under exhaustive exercise,and reduce the effect of myocarditis.Ultrastructural pathomorphology can significantly improve the structure of myocardial mitochondria and myofibrils,and improve mitochondrial function.It is suggested that electroacupuncture preconditioning has a positive effect on myocardial protection and structural and functional recovery.3.Mitochondrial AMPK/PGC-1 a signal transduction pathway was involved in the pathological changes of myocardial injury rats after exhaustive exercise,and the expression of AMPK decreased after exhaustive exercise.The expression of factors involved in mitochondrial synthesis downstream of AMPK/PGC-1 a signal transduction pathway was also inhibited.Electroacupuncture pretreatment could significantly up-regulate the expression of AMPK.It is suggested that the protective mechanism of electroacupuncture preconditioning on myocardium may be related to AMPK/PGC,1 a signal transduction pathway.4.Both electroacupuncture preconditioning and AMPK agonist AICAR could down-regulate the expression of serum markers of myocardial injury under exhaustive exercise,decrease the effect of myocarditis,improve mitochondrial function,and significantly improve the structure of myocardial mitochondria and myofibrils.It has a positive effect on myocardial protection and structural and functional recovery.It is suggested that electroacupuncture preconditioning may have the same protective effect as AICAR,and its mechanism may involve AMPK/PGC-1 a signal transduction pathway.5.At the same time,there was significant difference between AMPK inhibitor Compound C group and electroacupuncture pretreatment+Compound C group,which indicated that electroacupuncture pretreatment might have antagonistic effect on AMPK inhibitor Compound C.
Keywords/Search Tags:Exhaustive exercise, Exercise myocardial injury, Electroacupuncture preconditioning, AMPK/PGC-1α signal transduction pathway
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