Objectives:Skeletal muscle ischemia/reperfusion injury(IRI)occurs as a result of a marked reduction in arterial perfusion to a limb and can lead to tissue death and threaten limb viability.This work assessed the effec...Objectives:Skeletal muscle ischemia/reperfusion injury(IRI)occurs as a result of a marked reduction in arterial perfusion to a limb and can lead to tissue death and threaten limb viability.This work assessed the effects of 20-hydroxyecdysone(20E)on hindlimb skeletal tissue following tourniquet-induced ischemia/reperfusion injury.Methods:Animals were divided into 4 groups—control group(Control),Control+20E(C+20E),mice with IRI(IRI),and mice with IRI+20E(IRI+20E).IRI was modeled by applying a tourniquet to the hind limb for 2 h with reperfusion for 1 h.5 mg/kg of 20E was administered intraperitoneally for 14 days.Afterward,the physical activity of mice,the histological structure of the quadriceps femoris,the expression of genes encoding proteins induced by hypoxia and involved in tissue adaptation to ischemia,and the functional parameters of skeletal muscle mitochondria were assessed.Results:It was shown that IRI of the limbs leads to functional disorders,depression of muscle function,accumulation of malondialdehyde(MDA)in mitochondria,and a decrease in their Ca2+buffering capacity,as well as an increase in the expression of HIF-1α,VGEF-A,PGC1αand PDGF-BB genes associated with adaptation to ischemia.20E reduced the intensity of degenerative processes in skeletal muscles,which was expressed in a decrease in the number of centrally nucleated fibers.Analysis of gene expression levels indicated a high degree of adaptation of animals to IRI.20E reduced the level of MDA in mitochondria,but did not affect the rate of respiration and calcium retention capacity of organelles both in normal conditions and during IRI.Conclusion:20E partially alleviates the skeletal muscle damage caused by IRI and can be used as part of combination therapy.展开更多
Objectives:Duchenne muscular dystrophy(DMD)is characterized by the development of cardiac pathology secondarily expressed in mitochondrial dysfunction.DMD treatment includes support for mitochondrial function.The purp...Objectives:Duchenne muscular dystrophy(DMD)is characterized by the development of cardiac pathology secondarily expressed in mitochondrial dysfunction.DMD treatment includes support for mitochondrial function.The purpose of this work was to evaluate the effects of the lipophilic cation MKT-077,capable of modulating mitochondrial activity,on the structure and function of cardiac mitochondria in mdx and wild-type mice,as well as the state of this organ.Methods:Animals were divided into 4 groups:wild type(WT),WT+5 mg/kg MKT-077,mdx,mdx+5 mg/kg MKT-077.MKT-077 was administered intraperitoneally daily for 28 days.Finally,we assessed the parameters of the functioning of the cardiac mitochondria of mice,the expression of genes encoding proteins involved in mitochondrial communication,as well as the histology and ultrastructure of the myocardium and heart rate.Results:MKT-077 was shown to reverse mitochondrial hyperfunctionalization in mdx mice,reducing respiratory parameters to WT levels.MKT-077 also inhibited mitochondrial respiration in the hearts of WT mice.MKT-077 administration was accompanied by a tendency to normalize calcium retention capacity in the cardiac mitochondria of mdx mice.Myocardial ultrastructure and gene signature of mdx+MKT077 animals demonstrated increased mitophagy.We noted changes in the sarcoplasmic reticulum(SR)/mitochondria contacts,accompanied by differential changes in the level of genes encoding proteins involved in the communication of these organelles.This effect of MKT-077 was accompanied by normalization of the relative heart weight of mdx mice,a decrease in the level of fibrosis,and a tendency toward normalization of heart rate.Conclusion:MKT-077-induced reversal of cardiac mitochondrial hyperfunctionalization in mdx mice may promote a healthy-like state of the myocardium in these animals.展开更多
基金supported by a grant from the Russian Science Foundation(23-75-01061)。
文摘Objectives:Skeletal muscle ischemia/reperfusion injury(IRI)occurs as a result of a marked reduction in arterial perfusion to a limb and can lead to tissue death and threaten limb viability.This work assessed the effects of 20-hydroxyecdysone(20E)on hindlimb skeletal tissue following tourniquet-induced ischemia/reperfusion injury.Methods:Animals were divided into 4 groups—control group(Control),Control+20E(C+20E),mice with IRI(IRI),and mice with IRI+20E(IRI+20E).IRI was modeled by applying a tourniquet to the hind limb for 2 h with reperfusion for 1 h.5 mg/kg of 20E was administered intraperitoneally for 14 days.Afterward,the physical activity of mice,the histological structure of the quadriceps femoris,the expression of genes encoding proteins induced by hypoxia and involved in tissue adaptation to ischemia,and the functional parameters of skeletal muscle mitochondria were assessed.Results:It was shown that IRI of the limbs leads to functional disorders,depression of muscle function,accumulation of malondialdehyde(MDA)in mitochondria,and a decrease in their Ca2+buffering capacity,as well as an increase in the expression of HIF-1α,VGEF-A,PGC1αand PDGF-BB genes associated with adaptation to ischemia.20E reduced the intensity of degenerative processes in skeletal muscles,which was expressed in a decrease in the number of centrally nucleated fibers.Analysis of gene expression levels indicated a high degree of adaptation of animals to IRI.20E reduced the level of MDA in mitochondria,but did not affect the rate of respiration and calcium retention capacity of organelles both in normal conditions and during IRI.Conclusion:20E partially alleviates the skeletal muscle damage caused by IRI and can be used as part of combination therapy.
基金supported by a grant from the Russian Science Foundation(23-75-10006).
文摘Objectives:Duchenne muscular dystrophy(DMD)is characterized by the development of cardiac pathology secondarily expressed in mitochondrial dysfunction.DMD treatment includes support for mitochondrial function.The purpose of this work was to evaluate the effects of the lipophilic cation MKT-077,capable of modulating mitochondrial activity,on the structure and function of cardiac mitochondria in mdx and wild-type mice,as well as the state of this organ.Methods:Animals were divided into 4 groups:wild type(WT),WT+5 mg/kg MKT-077,mdx,mdx+5 mg/kg MKT-077.MKT-077 was administered intraperitoneally daily for 28 days.Finally,we assessed the parameters of the functioning of the cardiac mitochondria of mice,the expression of genes encoding proteins involved in mitochondrial communication,as well as the histology and ultrastructure of the myocardium and heart rate.Results:MKT-077 was shown to reverse mitochondrial hyperfunctionalization in mdx mice,reducing respiratory parameters to WT levels.MKT-077 also inhibited mitochondrial respiration in the hearts of WT mice.MKT-077 administration was accompanied by a tendency to normalize calcium retention capacity in the cardiac mitochondria of mdx mice.Myocardial ultrastructure and gene signature of mdx+MKT077 animals demonstrated increased mitophagy.We noted changes in the sarcoplasmic reticulum(SR)/mitochondria contacts,accompanied by differential changes in the level of genes encoding proteins involved in the communication of these organelles.This effect of MKT-077 was accompanied by normalization of the relative heart weight of mdx mice,a decrease in the level of fibrosis,and a tendency toward normalization of heart rate.Conclusion:MKT-077-induced reversal of cardiac mitochondrial hyperfunctionalization in mdx mice may promote a healthy-like state of the myocardium in these animals.
