Histological and biochemical outcomes of cardiac pathology in mdx mice with dietary quercetin enrichment
Histological and biochemical outcomes of cardiac pathology in mdx mice with dietary quercetin enrichment
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DOI：
10.1113/expphysiol.2014.083360
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发表时间：
2015-01-01
影响因子：
2.7
通讯作者：
Quindry, John C.
中科院分区：
文献类型：
--
作者：
Ballmann, Christopher;Hollinger, Katrin;Quindry, John C.
Duchenne肌营养不良症患者患有心脏病理，由于纤维化和心脏并发症，最多可导致所有死亡的40％。槲皮素是一种具有抗炎和抗氧化作用的黄酮醇，也是过氧化物酶体增殖物激活的受体共振剂的激活剂，能够抗氧化剂上调，线粒体生物发生和心脏并发症的预防。我们试图确定饮食中槲皮素富集阻止（实验1）并在MDX小鼠中挽救心脏病理（实验2）的程度。在实验1中，喂食对照盘（C3W6M，n = 10）或含有0.2％槲皮素的Chow喂食6个月（Q3W6M，n = 10）。在实验2中，喂食3个月大的MDX小鼠（C3m6m，n = 10）或含有0.2％槲皮素的0.2％Chow 6个月（Q3m6m，n = 10）。切除心脏进行组织学和生化分析。在实验1中，与C3W6M相比，Q3W6M小鼠的蛋白质印迹靶标在Q3W6M小鼠中增加了线粒体生物发生（细胞染料，P = 0.007）和抗氧化剂表达（超氧化物歧化酶2，p = 0.014）。组织学表明，与C36M相比，Q3W6M小鼠的乌托芬蛋白增加（P = 0.025）和降低了Q3W6M小鼠的基质金属蛋白酶9的丰度（P = 0.040）。在实验2中，与C3M6M相比，Q3M6M小鼠的相对（P = 0.023）和绝对心重（P = 0.020）降低。在Q3M6M小鼠中，损伤的适应症（降久毒素和曙红染色切片，p = 0.007）和转化生长因子1（p = 0.009）的蛋白质印迹分析减少了。六个月的槲皮素喂养增加了线粒体生物标志物，抗氧化剂蛋白和乌托蛋白，并减少了年轻小鼠的基质金属蛋白酶9。鉴于这些适应与减弱的心脏病理和损害有关，目前的发现可能表明饮食槲皮素富集会减弱营养不良的心脏病理学，但需要生理证实。
Patients with Duchenne muscular dystrophy suffer from cardiac pathology, which causes up to 40% of all deaths because of fibrosis and cardiac complications. Quercetin is a flavonol with anti-inflammatory and antioxidant effects and is also an activator of peroxisome proliferator-activated receptor coactivator1 capable of antioxidant upregulation, mitochondrial biogenesis and prevention of cardiac complications. We sought to determine the extent to which dietary quercetin enrichment prevents (experiment1) and rescues cardiac pathology (experiment2) in mdx mice. In experiment1, 3-week-old mdx mice were fed control chow (C3w6m, n=10) or chow containing 0.2% quercetin for 6 months (Q3w6m, n=10). In experiment2, 3-month-old mdx mice were fed control chow (C3m6m, n=10) or 0.2% chow containing 0.2% quercetin for 6 months (Q3m6m, n=10). Hearts were excised for histological and biochemical analyses. In experiment1, Western blot targets for mitochondrial biogenesis (cytochromec, P=0.007) and antioxidant expression (superoxide dismutase2, P=0.014) increased in Q3w6m mice compared with C3w6m. Histology revealed increased utrophin (P=0.025) and decreased matrix metalloproteinase9 abundance (P=0.040) in Q3w6m mice compared with C3w6m. In experiment2, relative (P=0.023) and absolute heart weights (P=0.020) decreased in Q3m6m mice compared with C3m6m. Indications of damage (Haematoxylin- and Eosin-stained sections, P=0.007) and Western blot analysis of transforming growth factor1 (P=0.009) were decreased in Q3m6m mice. Six months of quercetin feeding increased a mitochondrial biomarker, antioxidant protein and utrophin and decreased matrix metalloproteinase9 in young mice. Given that these adaptations are associated with attenuated cardiac pathology and damage, the present findings may indicate that dietary quercetin enrichment attenuates dystrophic cardiac pathology, but physiological confirmation is needed.