Effects of NVP-BEZ235 on pulmonary perivascular mast cells in hypoxia rats

CHAI Xiaoyu; HAN Qian; WU Yanping; WANG Xiang; LIU Xinmin

doi:10.3969/j.issn.1006-0111.2017.05.005

Message Board

Respected readers, authors and reviewers, you can add comments to this page on any questions about the contribution, review, editing and publication of this journal. We will give you an answer as soon as possible. Thank you for your support!

Name

E-mail

Phone

Title

Content

Verification Code

Objective To assess the effects of PI3K/mTOR dual inhibitor NVP-BEZ235 on the distribution and degranulation of perivascularmast cells in the lung of hypobaric hypoxia rats. Methods SD male rats in the hypoxia group were raised in the specific hypoxic incubator (50.5 kPa).The intervene group received NVP-BEZ235 training (35 mg/kg) intervention once every two days.The control group was fed in the conditions comparable to the other groups at local pressure and normoxia environment. After 21 days, all rats were sacrificed with injection of 5% pentobarbital sodium. Lung tissues were fixed and embedded in paraffin for further hematoxylin-eosin staining and toluidine blue staining. Results Compared with the control group, the number of pulmonary perivascular mast cells in the hypoxia group increased significantly. Hypoxia group had more mast cell accumulation and larger degranulation ratio around different diameters of pulmonary vessels (less than 50 μm, 50-100 μm, larger than 100 μm) than the control group (P< 0.05).The mast cell numbers decreased in NVP-BEZ235 intervention group compared with hypoxia group (P<0.05).The degranulation ratio of pulmonary vascular mast cells around 50-100 μm in the intervention group was smaller than the hypoxia group (P=0.000 3). Conclusion NVP-BEZ235 inhibits the aggregation of pulmonary perivascular mast cells and degranulation ratio of median diameter pulmonary perivascular mast cells in hypobaric hypoxia rats.

Effects of NVP-BEZ235 on pulmonary perivascular mast cells in hypoxia rats

Department of Geriatrics, First Hospital of Peking University, Beijing 100034, China

Received Date: 2016-11-01

Rev Recd Date: 2017-03-21

Key words:

Abstract: Objective To assess the effects of PI3K/mTOR dual inhibitor NVP-BEZ235 on the distribution and degranulation of perivascularmast cells in the lung of hypobaric hypoxia rats. Methods SD male rats in the hypoxia group were raised in the specific hypoxic incubator (50.5 kPa).The intervene group received NVP-BEZ235 training (35 mg/kg) intervention once every two days.The control group was fed in the conditions comparable to the other groups at local pressure and normoxia environment. After 21 days, all rats were sacrificed with injection of 5% pentobarbital sodium. Lung tissues were fixed and embedded in paraffin for further hematoxylin-eosin staining and toluidine blue staining. Results Compared with the control group, the number of pulmonary perivascular mast cells in the hypoxia group increased significantly. Hypoxia group had more mast cell accumulation and larger degranulation ratio around different diameters of pulmonary vessels (less than 50 μm, 50-100 μm, larger than 100 μm) than the control group (P< 0.05).The mast cell numbers decreased in NVP-BEZ235 intervention group compared with hypoxia group (P<0.05).The degranulation ratio of pulmonary vascular mast cells around 50-100 μm in the intervention group was smaller than the hypoxia group (P=0.000 3). Conclusion NVP-BEZ235 inhibits the aggregation of pulmonary perivascular mast cells and degranulation ratio of median diameter pulmonary perivascular mast cells in hypobaric hypoxia rats.

HTML

Reference (14)

[1]	Maxova H, Herget J, Vizek M. Lung mast cells and hypoxic pulmonary hypertension［J］. Physiol Res, 2012, 61 (1):1-11.
[2]	Humbert M, Montani D, Evgenov OV, et al. Definition and classification of pulmonary hypertension［J］. Handb Exp Pharmacol, 2013, 218:3-29.
[3]	Poor HD, Girgis R, Studer SM. World Health Organization Group Ⅲ pulmonary hypertension［J］. Prog Cardiovasc Dis, 2012, 55 (2):119-127.
[4]	Hoffmann J, Yin J, Kukucka M, et al. Mast cells promote lung vascular remodelling in pulmonary hypertension［J］. Eur Respir J, 2011, 37 (6):1400-1410.
[5]	Karar J, Cerniglia GJ, Lindsten T, et al. Dual PI3K/mTOR inhibitor NVP-BEZ235 suppresses hypoxia-inducible factor (HIF)-1 alpha expression by blocking protein translation and increases cell death under hypoxia［J］. Cancer Biol Ther, 2012, 13 (11):1102-1111.
[6]	Fang X, Li K, Tao X, et al. Effects of phosphoinositide 3-kinase on protease-induced acute and chronic lung inflammation, remodeling, and emphysema in rats［J］. Chest, 2013, 143 (4):1025-1035.
[7]	Blatt K, Herrmann H, Mirkina I, et al. The PI3-kinase/mTOR-targeting drug NVP-BEZ235 inhibits growth and IgE-dependent activation of human mast cells and basophils［J］. PLoS One, 2012, 7 (1):e29925.
[8]	Council NR. Guide for the care and use of laboratory animals［M］.8th Ed. Washington DC:National Academies Press,2011:11-151.
[9]	Tucker A, Mcmurtry IF, Alexander AF, et al. Lung mast cell density and distribution in chronically hypoxic animals［J］. J Appl Physiol Respir Environ Exerc Physiol, 1977, 42 (2):174-178.
[10]	Bartelds B, Van Loon RL, Mohaupt S, et al. Mast cell inhibition improves pulmonary vascular remodeling in pulmonary hypertension［J］. Chest, 2012, 141 (3):651-660.
[11]	Maira SM, Stauffer F, Brueggen J, et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity［J］. Mol Cancer Ther, 2008, 7 (7):1851-1863.
[12]	Nathan SD, Hassoun PM. Pulmonary hypertension due to lung disease and/or hypoxia［J］. Clin Chest Med, 2013, 34 (4):695-705.
[13]	Jin H, Wang Y, Zhou L, et al. Melatonin attenuates hypoxic pulmonary hypertension by inhibiting the inflammation and the proliferation of pulmonary arterial smooth muscle cells［J］. J Pineal Res, 2014, 57 (4):442-450.
[14]	Stenmark KR, Fagan KA, Frid MG. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms［J］. Circ Res, 2006, 99 (7):675-691.

Message Board

Effects of NVP-BEZ235 on pulmonary perivascular mast cells in hypoxia rats

doi: 10.3969/j.issn.1006-0111.2017.05.005

Abstract

References

Proportional views

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Related

Proportional views