Lung fibrosis induced by mechanical ventilation with different tidal volume in neonatal rats
HUANG Jin-Jie, WU Ben-Qing, DING Lu, CHEN Li
Department of Neonatology, Shenzhen People′s Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, China. Email:wubenqing783@126.com
Abstract 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.[Chin J Contemp Pediatr, 2010, 12 (10):799-803]
HUANG Jin-Jie,WU Ben-Qing,DING Lu et al. Lung fibrosis induced by mechanical ventilation with different tidal volume in neonatal rats[J]. 中国当代儿科杂志, 2010, 12(10): 799-803.
HUANG Jin-Jie,WU Ben-Qing,DING Lu et al. Lung fibrosis induced by mechanical ventilation with different tidal volume in neonatal rats[J]. CJCP, 2010, 12(10): 799-803.
[1]Thomas W, Speer CP. Nonventilatory strategies for prevention and treatment of bronchopulmonary dysplasia--what is the evidence?[J].Neonatology, 2008, 94(3): 150-159.
[2]Lionetti V, Recchia FA, Ranieri VM. Overview of ventilator-induced lung injury mechanisms[J].Curr Opin Crit Care, 2005, 11(1):82-86.
[3]Belperio JA,Keane MP,Lynch JP,Strieter RM.The role of cytokines during the pathogenesis of ventilator-associated and ventilator-induced lung injury[J].Semin Respir Crit Care Med,2006,27(4):350-364.
[4]Deakins KM. Bronchopulmonary dysplasia[J]. Respir Care, 2009,54(9):1252-1262.
[5]Strieter RM, Mehrad B. New mechanisms of pulmonary fibrosis[J]. Chest, 2009, 136(5): 1364-1370.
[6]Nin N, Lorente JA, de Paula M, El Assar M, Vallejo S, Pe~nuelas O,et al. Rats surviving injurious mechanical ventilation show reversible pulmonary, vascular and inflammatory changes[J]. Intensive Care Med, 2008, 34(5): 948-956.
[7]Dolinay T, Wu W, Kaminski N,Ifedigbo E, Kaynar AM, Szilasi M,et al.Mitogen-activated protein kinases regulate susceptibility to ventilator-induced lung injury[J]. PLoS One, 2008, 3(2):e1601.
[8]Wu S, Capasso L, Lessa A, Peng J, Kasisomayajula K, Rodriguez M, et al. High tidal volume ventilation activates smad 2 and upregulates expression of connective tissue growth factor in newborn rat lung[J].Pediatr Res, 2008, 63(3): 245-250.
[9]Belperio JA, Keane MP, Burdick MD, Londhe V, Xue YY, Li K,et al.Critical role for CXCR2 and CXCR2 ligands during the pathogenesis of ventilator-induced lung injury[J]. J Clin Invest, 2002, 110(11): 1703-1716.
[10]Schreiber T, Niemann C, Schmidt B, Karzai W. A novel model of selective lung ventilation to investigate the long-term effects of ventilation-induced lung injury[J]. Shock,2006,26(1):50-54.
[11]Wolthuis EK,Vlaar AP,Choi G.Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice[J].Crit Care, 2009,13(1):R1.
[13]Garcia CS, Abreu SC, Soares RM. Pulmonary morphofunctional effects of mechanical ventilation with high inspiratory air flow[J]. Crit Care Med, 2008, 36(1): 232-239.
[14]Santana MC,Garcia CS,Xisto DG,Nagato LK, Lassance RM, Prota LF,et al.Prone position prevents regional alveolar hyperinflation and mechanical stress and strain in mild experimental acute lung injury[J]. Respir Physiol Neurobiol, 2009, 167(2):181-188.
[15]Li LF, Liao SK, Huang CC, Hung MJ, Quinn DA. Serine/threonine kinase-protein kinase B and extracellular signal-regulated kinase regulate ventilator-induced pulmonary fibrosis after bleomycin-induced acute lung injury: a prospective, controlled animal experiment[J]. Crit Care, 2008, 12(4):R103.
[16]Mascaretti RS, Mataloun MM, Dolhnikoff M, Rebello CM. Lung morphometry, collagen and elastin content:changes after hyperoxic exposure in preterm rabbits[J]. Clinics (Sao Paulo),2009,64(11):1099-1104.
[18]Baguma-Nibasheka M, Kablar B. Pulmonary hypoplasia in the connective tissue growth factor (Ctgf) null mouse[J]. Dev Dyn, 2008, 237(2): 485-493.
[19]Wallace MJ, Probyn ME, Zahra VA. Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs[J].Respir Res,2009, 10(1):19.
[21]Sheikh S, Null D, Gentile D, Bimle C, Skoner D, McCoy K,et al. Urinary leukotriene E(4) excretion during the first month of life and subsequent bronchopulmonary dysplasia in premature infants[J]. Chest, 2001, 119(6): 1749-1754.
[22]Beller TC, Friend DS, Maekawa A, Lam BK, Austen KF, Kanaoka Y. Cysteinyl leukotriene 1 receptor controls the severity of chronic pulmonary inflammation and fibrosis[J]. Proc Natl Acad Sci USA, 2004, 101(9):3047-3052.
[23]Kanaoka Y, Boyce JA. Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses[J].J Immunol, 2004, 173(3): 1503-1510.
[24]Kato J, Kohyama T, Okazaki H, Desaki M, Nagase T, Rennard SI, et al. Leukotriene D4 potentiates fibronectin-induced migration of human lung fibroblasts[J].Clin Immunol, 2005, 117(2): 177-181.
[25]Akino K, Mineda T, Mori N, Hirano A, Imaizumi T, Akita S. Attenuation of cysteinyl leukotrienes induces human mesenchymal stem cell differentiation[J].Wound Repair Regen, 2006, 14(3):343-349.
[26]Yüksel H, Ozbilgin K, Coskun S, Tuglu I. Protective effect of leukotriene receptor antagonist montelukast on smoking-induced lung injury in Wistar rats[J].Acta Med Okayama,2003,57(1):13-19.