Paper Information

Journal:   IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES   MARCH 2018 , Volume 21 , Number 3; Page(s) 244 To 252.
 
Paper: 

CHRONIC INTERMITTENT HYPOBARIC HYPOXIA ATTENUATES MONOCROTALINE-INDUCED PULMONARY ARTERIAL HYPERTENSION VIA MODULATING INFLAMMATION AND SUPPRESSING NF-κB/P38 PATHWAY

 
 
Author(s):  GAO LEI, LIU JUN, HAO YONGMEI, ZHAO ZENGREN, TAN HUILIAN, ZHANG JIE, MENG NING, ZHENG QINGHOU, WANG ZHEN, ZHANG YI*
 
* DEPARTMENT OF PHYSIOLOGY, FOUNDATION MEDICINE SCHOOL OF HEBEI MEDICAL UNIVERSITY, SHIJIAZHUANG, 050017, CHINA
 
Abstract: 

Objective (s): Inflammation is involved in various forms of pulmonary arterial hypertension (PAH). Although the pathophysiology of PAH remains uncertain, NF-kB and p38 mitogen-activated protein kinase (p38 MAPK) has been reported to be associated with many inflammatory mediators of PAH. This study aimed to evaluate the effect of chronic intermittent hypobaric hypoxia (CIHH) on pulmonary inflammation and remodeling in monocrotaline (MCT) induced PAH in rats.
Materials and Methods: An in vivo model of PAH induced by MCT was employed. Statistical analyses were done using one-way analysis of variance (ANOVA) or Fisher's LSD test for multiple comparisons.
Results: Four weeks of CIHH exposure following MCT injection resulted in significant reduction of mean pulmonary artery pressure (mPAP) level and improvement of right ventricular hypertrophy (RVH). Morphometric analyses showed decreased wall thickness of pulmonary arterioles in MCT+CIHH treated rats. These findings are consistent with the decrease in Ki-67 immunostaining. Following CIHH treatments, apoptotic analysis showed a consistent decrease in T lymphocytes together with lower levels of CD4+ T cell subset as measured in spleen and blood samples. Furthermore, CIHH treatment resulted in markedly reduced expression of TNF-
a and IL-6 via the inhibition of NF-kB and p38 MAPK activity in rat lungs.
Conclusion: Altogether, these results provide new evidence relating to the mode of action of CIHH in the prevention of PAH induced by MCT.

 
Keyword(s): CHRONIC INTERMITTENT HYPOBARIC HYPOXIA, INFLAMMATION MONOCROTALINE, NF-κB, PULMONARY ARTERIA HYPERTENSION, P38, MAPK
 
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