[Study on the effect and mechanism of hypoxia on the histological structure of rat's lung]

OBJECTIVE; To observe the effect of intermittent normobaric hypoxia on the expression of transforming growth factor betal (TGF-beta1), Smad4, collagen I (Col I), tumor necrosis factor alpha (TNF-alpha) and on the changes in the histological structure of SPF SD Rat's lung.

Rats were placed in normal environment or intermittent normobaric hypoxia (101 kPa, 10% O2, 8 h every day) respectively. At the 3rd, 7th, 14th, 21st day, 5 rats from each group were killed and hematoxylin and eosin stain (HE stain) was applied to observe the pathological change in the lung of rats, immunohistochemical staining was used to detect the protein level of TGF-beta1, Col I. RT-PCR was performed to detect the mRNA levels of TGF-beta1 and Col I. Western blot to detect the expression of Smad4. Besides, the TNF-alpha in the bronchoalveolar lavage (BALF) were determined by ELISA.

Results of HE stain demonstrated that the mild edema and inflammatory cell infiltration appeared in the lung tissue at the 3rd day, and gradually aggravated inflammation were observed as the treated time extended; meanwhile the interalveolar septum become thicker and thicker as the time of exposing to normobaric hypoxia increased. Compared with the normoxia group, not only the protein expression of TGF-beta1, Smad4 and Col I, but also the mRNA expression of TGF-beta1 and Col I were elevated (P < 0.01) in normobaric hypoxia group as the treatment time extended. Besides, a positive correlation (r = 0.944, P < 0.01) between the protein level of TGF-beta1 and Smad4 was observed and an up-regulated TNF-alpha in the BALF was also noticed.

Normobaric hypoxia could cause pulmonary edema and inflammation by up-regulating expression of TNF-alpha, activating the TGF-beta1/Smads Signaling Pathway, and increasing the synthesization of Col I, the deposition of extracellular matrix as well as the interalveolar septum thickness.