Effect of pulmonary TNF-α overexpression on mouse isolated skeletal muscle function.
Effect of pulmonary TNF-α overexpression on mouse isolated skeletal muscle function.
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肺 TNF-α 过度表达对小鼠离体骨骼肌功能的影响。
DOI：
10.1152/ajpregu.00126.2011
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Hogan,MichaelC
中科院分区：
文献类型：
--
作者：
Zuo,Li;Nogueira,Leonardo;Hogan,MichaelC
肿瘤坏死因子-α是一种促炎细胞因子，参与包括慢性阻塞性肺疾病在内的多种病理过程。在本研究中，我们使用了一个在肺中过度表达肿瘤坏死因子-α(TG+)的转基因小鼠模型，以检验长期暴露于肿瘤坏死因子-α(如慢性阻塞性肺病)会降低骨骼肌力产生和疲劳抵抗力的假设，特别是在低氧条件下。在7-12个月时，TG+组的指长伸肌(EDL)和比目鱼肌的体重和肌肉重量均显著小于产仔野生型(WT)小鼠，但体重/肌肉重量比组间无差异。分别在高氧分压(∼)550Torr和低氧分压(∼40Torr)条件下对前交叉韧带和比目鱼肌进行疲劳收缩。尽管与高PO2相比，所有肌肉在低PO2时的抗疲劳能力都较低，但只有TG+小鼠(∼12%)的比目鱼肌疲劳速度比WT在高PO2时快。Tg+组小鼠∼最大张力比WT降低28-34%(两种Po2条件下均比WT降低28-34%)，但比目鱼肌仅在低Po2时这一参数较小(WT比WT降低31%)。在低氧状态下，TG+EDL肌肉的最大舒张率和最大收缩速率均显著低于WT EDL，而比目鱼肌的舒张率和收缩峰值无明显变化。这些结果表明，肺中肿瘤坏死因子-α的上调损害了外周骨骼肌的功能，但在高和低氧分压下对快肌和慢肌的影响不同。
TNF-α is a proinflammatory cytokine that is involved in numerous pathological processes including chronic obstructive pulmonary disease (COPD). In the present study, we used a transgenic mouse model that overexpresses TNF-α in the lung (Tg+) to test the hypothesis that chronic exposure to TNF-α (as seen in COPD) reduces skeletal muscle force production and fatigue resistance, particularly under low Po2conditions. At 7–12 mo, body and muscle weight of both extensor digitorum longus (EDL) and soleus were significantly smaller in Tg+compared with littermate wild-type (WT) mice; however, the body-to-muscle weight ratio was not different between groups. EDL and soleus muscles were subjected to in vitro fatiguing contractile periods under high (∼550 Torr) and low Po2(∼40 Torr). Although all muscles were less fatigue-resistant during low Po2compared with high Po2, only the soleus fatigued more rapidly in Tg+mice (∼12%) compared with WT at high Po2. The maximal tension of EDL was equally reduced in Tg+mice (28–34% decrease from WT under both Po2conditions); but for soleus this parameter was smaller only under low Po2in Tg+mice (∼31% decrease from WT). The peak rate of relaxation and the peak rate of contraction were both significantly reduced in Tg+EDL muscles compared with WT EDL under low Po2conditions, but not in soleus. These results demonstrate that TNF-α upregulation in the lung impairs peripheral skeletal muscle function but affects fast- and slow-twitch muscles differentially at high and low Po2.
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DOI：
--
发表时间：
1998
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
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通讯作者：
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DOI：
10.1152/jappl.1999.86.6.1812
发表时间：
1999
期刊：
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子：
--
作者：
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通讯作者：
Hogan,MC
影响因子：
15.9
作者：
RICHARDSON, RS;NOYSZEWSKI, EA;WAGNER, PD
通讯作者：
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影响因子：
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DOI：
--
发表时间：
2008
期刊：
Pflügers Archiv: European Journal of Physiology
影响因子：
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