[Changes of the actin and transforming growth factor-beta1 expression in the small airways of the rat with chronic obstructive lung disease].

OBJECTIVE: To study the roles of actin and transforming growth factor (TGF)-beta(1) in the injury repair and the development of emphysema. METHODS: Wistar rats were randomly divided into two groups: the smoking and infection group (group SI) and the control group (group C). The rats of group SI received smoking irritation accompanying with repeated intranasal infection. Subgroups of the experimental animals were killed in the 2nd, 4th, 8th and 16th weeks respectively. The morphological changes of lungs were compared and PaO(2), PaCO(2) as well as the right ventricular systolic pressure (RVSP) were analysed. The lung sections were stained with immunohistochemistry for actin and TGF-beta(1). RESULTS: In comparison with animals of group C, thickening of the bronchiolar walls, narrowing of bronchiolar lumens, and area of emphysema were much severe in animals of group SI (P < 0.05). The muscularization of intra-alveolar arteries in group SI in the 16th week was apparent in comparing with that in group C (P < 0.05). PaO(2) values in group SI were significantly decreased, and RVSP values in group SI were significantly increased in the 8th and 16th week (P < 0.05). Actin expression was increased in animals of group SI in the 4th and 8th week (0.24 +/- 0.06 and 0.25 +/- 0.05) in comparing with that of group C (0.09 +/- 0.03) (P < 0.05). Animals of group SI showed a significant increase of TGF-beta(1) in lung tissue in different periods as mentioned in above (33.33 +/- 12.11, 45.71 +/- 15.12, 71.43 +/- 16.76 and 86.25 +/- 20.66 respectively). CONCLUSIONS: The increased expression of actin and TGF-beta(1) protein in small airways induced by smoking irritation and Klebsiella Pneumoniae may interfere with the repair response, and contributes to the development of emphysema.

Expression of hypoxia-inducible factor-1 alpha and endothelin-1 gene in hypoxic pulmonary hypertension.

OBJECTIVE: To investigate the expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) and endothelin-1 (ET-1) gene in hypoxic pulmonary hypertension (HPH). METHODS: The animal model of HPH was replicated. The elastic fiber staining was applied to show the intraacinar pulmonary artery (IAPA). Radioimmunoassay (RIA) and in situ hybridization (ISH) were used for detection of HIF-1a and. ET-1. RESULTS: ISH showed that HIF-1alpha mRNA was expressed in the IAPA of all hypoxic rat. The expression was stronger in the H14 d (0.256 9 +/- 0.046 8) and H28 d (0.225 8 +/- 0.045 3) groups than in the H5 d (0.1455 +/- 0.072 2) and control (0.110 9 +/- 0.022 4) groups (P < 0.05), the expression of ET-1 mRNA in the H14 d (0.412 2 +/- 0.078 3) and H28 d (0.368 4 +/- 0.072 9) groups was also stronger than that in the H5 d (0.201 7 +/- 0.034 9) and control (0.185 5 +/- 0.036 1) groups (P < 0.05). The amount of ET-1 in pulmonary arteial blood in the H14 d [(158.78 +/- 25.14) pg/ml] and H28 d [(142.93 +/- 23.38) pg/ml] groups was significantly higher than that in the H5 d [(79.68 +/- 12.54) pg/ml] and control [(65.37 +/- 10.82) pg/ml] groups (P < 0.05). The mean pulmonary arterial pressure (mPAP) in the H14 d [(34.0 +/- 5.8) mm Hg] and H 28 d [(29.0 +/- 4.7) mm Hg] groups was markedly higher than that in the H5 d [(19.0 +/- 3.5) mm Hg] and control [(17.0 +/- 2.8) mm Hg] groups (P < 0.05). A positive rank correlation existed between the mPAP and the amount of ET-1 (rs = 0.747, P < 0.05). CONCLUSIONS: Expression of HIF-1alpha and ET-1 mRNA in IAPA increase under long-term hypoxic condition and both show consistent expression, indicating that the expression of HIF-1a and ET-1 gene contribute to pathogenesis of HPH.