Single intraperitoneal injection of monocrotaline as a novel large animal model of chronic pulmonary hypertension in Tibet minipigs.
Single intraperitoneal injection of monocrotaline as a novel large animal model of chronic pulmonary hypertension in Tibet minipigs.
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DOI：
10.1371/journal.pone.0078965
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li HT
中科院分区：
文献类型：
--
作者：
Zeng GQ;Liu R;Liao HX;Zhang XF;Qian YX;Liu BH;Wu QH;Zhao J;Gu WW;Li HT
本研究旨在通过单次腹腔注射野百合碱（monocrotaline，MCT）建立西藏小型幼猪慢性肺动脉高压动物模型，以实现有创和无创测量，为后续研究提供依据。24头小型猪（8周龄）随机接受12.0 mg/kg MCT（MCT组，n = 12）或安慰剂（对照组，各n=12）单次注射。 在第42天，用常规经胸超声心动图、右心导管插入术（RHC）和病理学变化评价所有动物的肺动脉高压。将这些研究的结果在两组之间进行比较。超声心动图显示，MCT组的肺动脉平均压（PAMP）显著高于对照组（P<0.001）。MCT处理的小型猪的肺动脉瓣曲线显示V形信号，a波减少。此外，MCT组肺动脉射血前期较长，加速时间和射血时间较短。RHC显示MCT组的平均肺动脉压（mPAP）高于对照组（P<0.01）。mPAP值与PAMP值呈正相关（R = 0.974，P<0.0001），与射血时间呈负相关（R = 0.680，P<0.0001）。 病理学显示MCT处理的小型猪中存在肺血管重塑和右心室肥大指数较高的证据。在注射MCT后6周，可在年轻小型猪中成功建立慢性肺动脉高压模型。这些小型猪模型表现出肺动脉高压的特征，可以通过有创（RHC）和无创（超声心动图）测量进行评估，并可用作未来肺动脉高压研究的简单而稳定的工具。
The purpose of this study was to establish an animal model of chronic pulmonary hypertension with a single-dose intraperitoneal injection of monocrotaline (MCT) in young Tibet minipigs, so as to enable both invasive and noninvasive measurements and hence facilitate future studies. Twenty-four minipigs (8-week-old) were randomized to receive single-dose injection of 12.0 mg/kg MCT (MCT group, n = 12) or placebo (control group, n = 12 each). On day 42, all animals were evaluated for pulmonary hypertension with conventional transthoracic echocardiography, right heart catheterization (RHC), and pathological changes. Findings of these studies were compared between the two groups. At echocardiography, the MCT group showed significantly higher pulmonary arterial mean pressure (PAMP) compared with the controls (P<0.001). The pulmonary valve curve showed v-shaped signals with reduction of a-waves in minipigs treated with MCT. In addition, the MCT group had longer pulmonary artery pre-ejection phases, and shorter acceleration time and ejection time. RHC revealed higher mean pulmonary arterial pressure (mPAP) in the MCT group than in the control group (P<0.01). A significant and positive correlation between the mPAP values and the PAMP values (R = 0.974, P<0.0001), and a negative correlation between the mPAP and ejection time (R = 0.680, P<0.0001) was noted. Pathology demonstrated evidence of pulmonary vascular remodeling and higer index of right ventricular hypertrophy in MCT-treated minipigs. A chronic pulmonary hypertension model can be successfully established in young minipigs at six weeks after MCT injection. These minipig models exhibited features of pulmonary arterial hypertension that can be evaluated by both invasive (RHC) and noninvasive (echocardiography) measurements, and may be used as an easy and stable tool for future studies on pulmonary hypertension.
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