Department of Applied Physiology and Kinesiology University of Florida, Gainesville, Florida, USA.
PLoS One. 2013 Apr 22;8(4):e62702. doi: 10.1371/journal.pone.0062702. Print 2013.
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.
肺动脉高压（PH）导致体重减轻和吸气（膈肌）肌肉功能障碍。药物（野百合碱，MCT）诱导的 PH 模型已广泛用于小鼠，以研究 PH 的病因。然而，尚不清楚 MCT 诱导的 PH 是否会在小鼠中重现患者中观察到的体重减轻和膈肌功能障碍。这是广泛使用小鼠来研究 PH 恶病质和膈肌异常的机制的前提条件。因此，我们在盐水（对照）或 MCT（600mg/kg）注射 6-8 周后测量了小鼠的体重和比目鱼肌重量、食物摄入量和膈神经收缩特性。PH 小鼠的体重逐渐减轻，而两组的食物摄入量相似。PH 降低了（P<0.05）膈神经最大等长比力、最大缩短速度和峰值功率。整个膈肌裂解物中的蛋白羰基和选定肌原纤维蛋白的丰度不受 PH 影响。我们的发现表明，MCT 诱导的 PH 小鼠模型存在膈肌等长和等张收缩异常。总体而言，MCT 诱导的 PH 小鼠模型模拟了 PH 患者报告的体重减轻和膈肌无力。
