Mitrou G I, Poulianiti K P, Koutedakis Y, Jamurtas A Z, Maridaki M D, Stefanidis I, Sakkas G K, Karatzaferi C
School of Physical Education and Sport Science, University of Thessaly, Trikala, Greece.
Biomechanical Solutions, Karditsa, Greece.
Hippokratia. 2017 Jan-Mar;21(1):3.
The exact causes of skeletal muscle weakness in chronic kidney disease (CKD) remain unknown with uremic toxicity and redox imbalances being implicated. To understand whether uremic muscle has acquired any sensitivity to acute redox changes we examined the effects of redox disturbances on force generation capacity.
Permeabilized single psoas fibers (N =37) from surgically induced CKD (UREM) and sham-operated (CON) rabbits were exposed to an oxidizing (10 mM Hydrogen Peroxide, HO) and/or a reducing [10 mM Dithiothreitol (DTT)] agent, in a blind design, in two sets of experiments examining: A) the acute effect of the addition of HO on maximal (pCa 4.4) isometric force of actively contracting fibers and the effect of incubation in DTT on subsequent re-activation and force recovery (N =9 CON; N =9 UREM fibers); B) the effect of incubation in HO on both submaximal (pCa 6.2) and maximal (pCa 4.4) calcium activated isometric force generation (N =9 CON; N =10 UREM fibers).
Based on cross-sectional area (CSA) calculations, a 14 % atrophy in UREM fibers was revealed; thus forces were evaluated in absolute values and corrected for CSA (specific force) values. A) Addition of HO during activation did not significantly affect force generation in any group or the pool of fibers. Incubation in DTT did not affect the CON fibers but caused a 12 % maximal isometric force decrease in UREM fibers (both in absolute force p =0.024, and specific force, p =0.027). B) Incubation in HO during relaxation lowered subsequent maximal (but not submaximal) isometric forces in the Pool of fibers by 3.5 % (for absolute force p =0.033, for specific force p =0.019) but not in the fiber groups separately.
Force generation capacity of CON and UREM fibers is affected by oxidation similarly. However, DTT significantly lowered force in UREM muscle fibers. This may indicate that at baseline UREM muscle could have already been at a more reduced redox state than physiological. This observation warrants further investigation as it could be linked to disease-induced effects. HIPPOKRATIA 2017, 21(1): 3-7.
慢性肾脏病（CKD）患者骨骼肌无力的确切原因尚不清楚，目前认为与尿毒症毒性和氧化还原失衡有关。为了解尿毒症肌肉是否对急性氧化还原变化具有敏感性，我们研究了氧化还原紊乱对肌力产生能力的影响。
在两项实验中，采用双盲设计，将手术诱导的CKD（UREM）兔和假手术（CON）兔的单个腰大肌通透纤维（N = 37）分别暴露于氧化试剂（10 mM过氧化氢，HO）和/或还原试剂[10 mM二硫苏糖醇（DTT）]中，实验一检测HO添加对主动收缩纤维最大（pCa 4.4）等长力的急性影响以及DTT孵育对随后再激活和肌力恢复的影响（N = 9条CON纤维；N = 9条UREM纤维）；实验二检测HO孵育对次最大（pCa 6.2）和最大（pCa 4.4）钙激活等长肌力产生的影响（N = 9条CON纤维；N = 10条UREM纤维）。
根据横截面积（CSA）计算，UREM纤维出现了14%的萎缩；因此，对肌力进行绝对值评估，并根据CSA（比肌力）值进行校正。A）激活过程中添加HO对任何组或纤维池的肌力产生均无显著影响。DTT孵育对CON纤维无影响，但导致UREM纤维最大等长力降低12%（绝对肌力p = 0.024，比肌力p = 0.027）。B）松弛过程中HO孵育使纤维池中随后的最大（而非次最大）等长力降低3.5%（绝对肌力p = 0.033，比肌力p = 0.019），但对各纤维组无此影响。
CON和UREM纤维的肌力产生能力受氧化作用的影响相似。然而，DTT显著降低了UREM肌纤维的肌力。这可能表明，在基线状态下，UREM肌肉的氧化还原状态可能已经比生理状态更还原。这一观察结果值得进一步研究，因为它可能与疾病诱导的效应有关。《希波克拉底》2017年，21(1): 3 - 7。
