PPARα Gene Polymorphism And MRNA Expression Level,Mitochondrial Respiratory Function,Ultrastructure In The Vastus Lateralis Muscle Of Patients With COPD

Objective:The aim of the present study was to explore the COPD patients PPARαgene five point rs45550937(C/G),rs45552534(A/G),rs45576140(C/G), rs45528736(A/G),rs45576734(A/G) polymorphism and mRNA expression in the vastus lateralis muscle(VL),beside,It's relationship with the muscle mitochondrial respiratory function,ultrastructure are being investigated.Methods:The PPARα's five point as presented above were assayed by Polymerase chain and sequencing methods between 123 case COPD patients and 61 case Age-matched controls in kunming.Then,6 cases of healthy control group (Control),8 case COPD with normal BMI(Body Mass Index,BMIN) and 6 cases of low BMI COPD(BMIL) patients come from above groups were randomly,both of them underwent open muscle biopsy,about 0.5-0.6g muscle specimens were obtained. Next,a part of the specimen(about 50mg) were performed real time PCR to detect the PPARαmRNA expression level.Another part of the the specimen(about 400mg) are use for extraction of muscle mitochondria by frozen centrifugal method,Clark oxygen electrode detected the mitochondrial respiratory function,according to the amount of mitochondrial respiration oxygen consumption conversion out of State 3 respiratory rate(ST3),State 4 respiratory rate(ST4),respiratory control rati(RCR,ST3/ST4).The rest muscle specimens(about 20-50mg),Mitochondrial number,fractional area and morphometry,as well as Z-line width(as a surrogate marker of fibre type),were analysed using transmission electron microscopy.Results:Both in COPD group and control group,PPARα's five point as appeared above were not detected mutation.The vastus lateralis PPARαmRNA expression level declined in the COPD group compared to the control(0.82±0.10 vs 0.54±0.16,p＜0.01),Stratified analysis we can see:comparison with BMIN,BMIL group expression level were decreased(64±0.09 vs 0.41±0.12,p=0.02);Yet,expression leve of Control group comparison with the BMIN group,there are not reach statistical significance(0.82±0.10 vs 64±0.09, p=0.12 ).Compared to the control and BMIN groups,RCR in the BMIL group were decreased(2.86±0.32vs5.13±0.35,2.86±0.32vs 3.97±0.51,p＜0.01 for each); Compared with control group,the RCR of BMI group were declined(5.13±0.35 vs 3.97±0.51,p＜0.01).Mitochondrial number,fractional area as well as Z-line widthwere reduced in the vastus of BMIL group.But in BMIN groups,those changes have not reach statistical significance.PPARαmRNA expression was positively correlated with RCR,Mitochondrial number,fractional area and Z-line width,(r=0.71,0.69,0.75,0.63.p＜0.01 respectively).Conclusion:The study demonstrates for the first time that the five PPARαgene loci polymorphism had no correlation with PPARαmRNA expression level of skeletal muscle atrophy COPD patient.At the same time,This is the first systematic describle the relationship between PPARαmRNA expression level with the mitochondrial respiratory function and muscle ultrastructure in both normal Body Mass Index and low Body Mass Index of COPD patient's peripheral skeletal muscle.COPD patients with normal skeletal muscle mass(FFMI assessment) display mitochondrial electron transport chain and oxidative phosphorylation(RCR assessment) abnormal,but the volume density of mitochondria was maintained,while in COPD patients with low body weight,Both of them were declined.That is to say, the abnormal of mitochondrial electron transport chain and mitochondrial oxidative phosphorylation prior to the decline of volume density of mitochondria is an early event in patients with COPD muscle dysfunction.PPARαgene mRNA expression level decreased,and related the decline of mitochondrial respiratory function and volume density.Perhaps,the reduction expression of PPARαgene is cause of skeletal muscle dysfunction in COPD patient.