Diaphragm atrophy and contractile dysfunction in a murine model of pulmonary hypertension.

Diaphragm atrophy and contractile dysfunction in a murine model of pulmonary hypertension.
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DOI:
10.1371/journal.pone.0062702
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Ferreira LF
Ferreira LF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ahn B;Empinado HM;Al-Rajhi M;Judge AR;Ferreira LF

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肺动脉高压 (PH) 会导致体重减轻和吸气(膈肌)肌功能障碍。药物(野百合碱,MCT)诱导的 PH 模型已广泛用于小鼠以检查 PH 的病因。然而,尚不清楚 MCT 在小鼠中诱导的 PH 是否会重现患者中出现的体重减轻和膈肌功能障碍。这是广泛使用小鼠来检查 PH 中恶病质和膈肌异常机制的先决条件。因此,我们测量了注射盐水(对照)或 MCT(600 mg/kg)6-8 周后小鼠的身体和比目鱼肌重量、食物摄入量和膈肌收缩特性。 PH 小鼠的体重逐渐下降,而两组的食物摄入量相似。 PH降低(P<0.05)隔膜最大等长比力、最大缩短速度和峰值功率。全隔膜裂解物中的蛋白质羰基和选定的肌原纤维蛋白质的丰度不受 PH 的影响。我们的研究结果表明,MCT 诱导的 PH 小鼠模型中膈肌等长收缩和等张收缩异常。总体而言,MCT 引发的 PH 小鼠模型模拟了 PH 患者报告的体重减轻和膈肌无力。
Pulmonary hypertension (PH) causes loss of body weight and inspiratory (diaphragm) muscle dysfunction. A model of PH induced by drug (monocrotaline, MCT) has been extensively used in mice to examine the etiology of PH. However, it is unclear if PH induced by MCT in mice reproduces the loss of body weight and diaphragm muscle dysfunction seen in patients. This is a pre-requisite for widespread use of mice to examine mechanisms of cachexia and diaphragm abnormalities in PH. Thus, we measured body and soleus muscle weight, food intake, and diaphragm contractile properties in mice after 6–8 weeks of saline (control) or MCT (600 mg/kg) injections. Body weight progressively decreased in PH mice, while food intake was similar in both groups. PH decreased (P<0.05) diaphragm maximal isometric specific force, maximal shortening velocity, and peak power. Protein carbonyls in whole-diaphragm lysates and the abundance of select myofibrillar proteins were unchanged by PH. Our findings show diaphragm isometric and isotonic contractile abnormalities in a murine model of PH induced by MCT. Overall, the murine model of PH elicited by MCT mimics loss of body weight and diaphragm muscle weakness reported in PH patients.
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