[Lung fibrosis induced by mechanical ventilation with different tidal volume in neonatal rats].
OBJECTIVE
To study the changes of collagen synthesis following mechanical ventilation with different tidal volume and the possible mechanism.


METHODS
Twenty-four neonatal Sprague-Dawley rats were randomized to hyperventilation (tidal volume 25 mL/kg), conventional ventilation (tidal volume 10 mL/kg) and no mechanical ventilation (control group) (n=8 each group). They were sacrificed 5 hrs after ventilation. Left lung samples were used for histopathologic examinations and the detection of connective tissue growth factor (CTGF) expression by immunohistochemistry. Right lung samples were used for the detection of expression of procollagenIII mRNA(PcolIII mRNA), cysteinyl leukotriene mRNA(CysLT1 mRNA)and CTGF mRNA by PCR.


RESULTS
The severity of lung injury and fibrosis increased significantly with the increasing tidal volume compared with the control group. Lung CTGF mRNA expression in the hyperventilation group was significantly higher than that in the control group (P<0.05). Lung PcolIII mRNA and CysLT1 mRNA levels increased with the increasing tidal volume when compared with the control group. The differences in PcolIII mRNA and CysLT1 mRNA levels between groups were significant (P<0.05). There was a positive correlation between lung PcolIII mRNA expression and the severity of lung injury (r=0.78,P<0.01). CTGF and CysLT levels were positively correlated with PcolIII expression (r = 0.59,0.86,P<0.01).


CONCLUSIONS
Mechanical ventilation using different tidal volume leads to different severities of lung injury, followed by the occurrence of lung fibrosis. The degree of lung fibrosis is consistent with the severity of lung injury. CysLT and CTGF may be involved in the development of lung fibrosis.
Department of Neonatology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China.
Jin-Jie
JJ
Huang
Ben-Qing
BQ
Wu
Lu
L
Ding
Li
L
Chen
D000818:Animals; D000831:Animals, Newborn; D024061:Collagen Type III / Q000235:genetics; D055513:Connective Tissue Growth Factor / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D015289:Leukotrienes / Q000235:genetics; D008168:Lung / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D013990:Tidal Volume
C526316:CCN2 protein, rat; D024061:Collagen Type III; D015289:Leukotrienes; D012333:RNA, Messenger; C112381:cysteinyl-leukotriene; D055513:Connective Tissue Growth Factor; D003545:Cysteine