Pathological changes in pulmonary circulation in carbon tetrachloride (CCl4)-induced cirrhotic mice.
Pathological changes in pulmonary circulation in carbon tetrachloride (CCl4)-induced cirrhotic mice.
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DOI：
10.1371/journal.pone.0096043
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Dranoff JA
中科院分区：
文献类型：
--
作者：
Das M;Boerma M;Goree JR;Lavoie EG;Fausther M;Gubrij IB;Pangle AK;Johnson LG;Dranoff JA
Lack of an experimental model of portopulmonary hypertension (POPH) has been a major obstacle in understanding of pathophysiological mechanisms underlying the disease. We investigated the effects of CCl4-mediated cirrhosis on the pulmonary vasculature, as an initial step towards an improved understanding of POPH. Male C57BL/6 mice received intraperitoneal injection of either sterile olive oil or CCl4 3 times/week for 12 weeks. Cirrhosis and portal hypertension were confirmed by evidence of bridging fibrosis and nodule formation in CCl4-treated liver determined by trichrome/picrosirius red staining and an increase in spleen weight/body weight ratio, respectively. Staining for the oxidative stress marker, 4-hydroxynonenal (4-HNE), was strong in the liver but was absent in the lung, suggesting that CCl4 did not directly induce oxidative injury in the lung. Pulmonary acceleration time (PAT) and the ratio of PAT/pulmonary ejection time (PET) measured by echocardiography were significantly decreased in cirrhotic mice. Increase in right ventricle (RV) weight/body weight as well as in the weight ratio of RV/(left ventricle + septum) further demonstrated the presence of pathological changes in the pulmonary circulation in these mice. Histological examination revealed that lungs of cirrhotic mice have excessive accumulation of perivascular collagen and thickening of the media of the pulmonary artery. Collectively, our data demonstrate that chronic CCl4 treatment induces pathological changes in pulmonary circulation in cirrhotic mice. We propose that this murine cirrhotic model provides an exceptional tool for future studies of the molecular mechanisms mediating pulmonary vascular diseases associated with cirrhosis and for evaluation of novel therapeutic interventions.
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影响因子：
2.6
作者：
Das M;Fessel J;Tang H;West J
通讯作者：
West J
影响因子：
29.4
作者：
Berzigotti, Annalisa;Seijo, Susana;Bosch, Jaime
通讯作者：
Bosch, Jaime
DOI：
10.1152/ajplung.00114.2010
发表时间：
2010-09-01
影响因子：
4.9
作者：
Urboniene, Dalia;Haber, Idith;Archer, Stephen L.
通讯作者：
Archer, Stephen L.
影响因子：
4.6
作者：
Ma, Changqing;Crippin, Jeffrey S.;Brunt, Elizabeth M.
通讯作者：
Brunt, Elizabeth M.
影响因子：
--
作者：
Ferrari, Renata Salatti;da Rosa, Darlan Pase;Marroni, Norma Possa
通讯作者：
Marroni, Norma Possa