Low dose monocrotaline causes a selective pulmonary vascular lesion in male and female pneumonectomized rats.
Low dose monocrotaline causes a selective pulmonary vascular lesion in male and female pneumonectomized rats.
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低剂量野百合碱对肺切除大鼠肺血管的选择性损伤。
DOI：
10.1080/01902148.2017.1422157
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发表时间：
2018-03
影响因子：
1.7
通讯作者：
White RJ
中科院分区：
文献类型：
--
作者：
Lachant DJ;Meoli DF;Haight D;Lyons JA;Swarthout RF;White RJ
低剂量（30-80 mg/kg）的野百合碱通常用于在大鼠中建立肺动脉高压的实验模型。在这些剂量下，野百合碱引起肺内皮细胞凋亡和急性肺损伤，其最终解决成肺血管疾病。已知较高剂量的野百合碱（300 mg/kg）会造成严重的肝损伤，但先前使用较低剂量的研究尚未报告其他器官的组织学，以确定野百合碱的血管损伤是肺选择性的还是全身性的。因此，我们试图确定在肺动脉高压研究中常用的剂量下野百合碱是否会引起肺外损伤。我们对年轻的雄性和雌性大鼠进行左肺切除术，然后在7天后给予50-60 mg/kg野百合碱。我们在前3周监测血清化学和尿试纸，而动物发展肺动脉高压。3周后，我们处死动物，对肺和高血管内脏器官（肾、肝和脾）进行弹性蛋白染色，以评估血管损伤和重塑的程度。我们没有观察到蛋白尿或显着转氨酶超过3周后野百合碱。如以前发表的，野百合碱引起严重的肺血管疾病与新生内膜病变和中膜肥大。我们没有发现肾脏、肝脏或脾脏中有明显的大动脉或小动脉损伤。两名外部兽医病理学家未在这些大鼠的肾脏、肝脏或脾脏中发现组织病理学。我们的结论是，50-60毫克/公斤的野百合碱导致选择性肺血管病变，雄性和雌性大鼠在这些剂量的野百合碱在3周内几乎没有非肺损伤。
Low doses (30–80 mg/kg) of monocrotaline are commonly used to create experimental models of pulmonary hypertension in rats. At these doses, monocrotaline causes pulmonary endothelial apoptosis and acute lung injury which ultimately resolves into pulmonary vascular disease. Higher doses of monocrotaline (300 mg/kg) are known to create severe liver injury, but previous investigations with lower doses have not reported histology in other organs to determine whether the vascular injury with monocrotaline is pulmonary-selective or generalized. We therefore sought to determine whether monocrotaline caused extra-pulmonary injury at doses commonly used in pulmonary hypertension studies. We performed left pneumonectomy on young male and female rats before administering 50–60 mg/kg monocrotaline 7 days later. We monitored serum chemistry and urine dipsticks during the first 3 weeks while the animals developed pulmonary hypertension. After 3 weeks, we sacrificed animals and stained the lungs and highly vascular visceral organs (kidney, liver, and spleen) for elastin to evaluate the degree of vascular injury and remodeling. We did not observe proteinuria or significant transaminitis over the 3 weeks following monocrotaline. As previously published, monocrotaline caused severe pulmonary vascular disease with neointimal lesions and medial hypertrophy. We did not identify significant large or small arterial damage in the kidneys, liver, or spleen. Two external veterinary pathologists did not identify histopathology in the kidneys, liver, or spleen of these rats. We conclude that 50–60 mg/kg of monocrotaline causes a selective pulmonary vascular lesion and that male and female rats have little non-pulmonary damage over 3 weeks at these doses of monocrotaline.
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DOI：
10.1164/rccm.201607-1515pp
发表时间：
2017-03-01
影响因子：
24.7
作者：
Bonnet, Sebastien;Provencher, Steeve;Humbert, Marc
通讯作者：
Humbert, Marc
DOI：
10.1007/bf02899076
发表时间：
1989-01-01
期刊：
VIRCHOWS ARCHIV B-CELL PATHOLOGY INCLUDING MOLECULAR PATHOLOGY
影响因子：
--
作者：
MOLTENI, A;WARD, WF;SOLLIDAY, NH
通讯作者：
SOLLIDAY, NH
影响因子：
3.8
作者：
ROTH, RA;DOTZLAF, LA;HOOK, JB
通讯作者：
HOOK, JB
影响因子：
3.1
作者：
Dumitrascu R;Koebrich S;Dony E;Weissmann N;Savai R;Pullamsetti SS;Ghofrani HA;Samidurai A;Traupe H;Seeger W;Grimminger F;Schermuly RT
通讯作者：
Schermuly RT
影响因子：
10.8
作者：
Aliotta, Jason M.;Pereira, Mandy;Klinger, James R.
通讯作者：
Klinger, James R.