不同潮气量通气启动新生鼠肺纤维化的特点

摘要
图/表
参考文献(26)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (1396 KB)
输出: BibTeX | EndNote (RIS) 背景资料

摘要目的：探讨不同潮气量机械通气后新生大鼠肺胶原合成的变化及其机制。方法：24只新生Sprague-Dawley大鼠随机分为对照组、常规通气组（潮气量10 mL/kg）及过度通气组（潮气量25 mL/kg），每组8只。机械通气5 h后处死，取肺组织，左肺行肺组织病理损伤评分,以免疫组织化学方法观察结缔组织生长因子（CTGF）表达。PCR法检测右肺组织Ⅲ型前胶原蛋白mRNA（PcolⅢ mRNA）、半胱氨酰白三烯mRNA（CysLT1 mRNA）及CTGF mRNA水平。结果：肺损伤程度和纤维化程度随着潮气量增加而增加(P<0.05）。与对照组比较，过度通气组肺组织CTGF mRNA水平显著性增高（P<0.05）。肺组织PcolⅢ mRNA 和 CysLT1 mRNA水平随潮气量增加而增加，各组间差异有统计学意义（P<0.05）。肺组织中PcolⅢ mRNA表达与肺组织病理损伤程度呈正相关关系（r=0.78，P<0.01）；CTGF、CysLT均和PcolⅢ呈正相关关系(r＝0.59，0.86，P<0.01)。结论：不同潮气量机械通气导致不同程度肺损伤，并启动肺纤维化。肺纤维化程度与肺损伤程度一致。肺纤维化的启动与CysLT作用和CTGF激活有关。［中国当代儿科杂志，2010，12（10）：799-803］

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	黄进洁
	吴本清
	丁璐
	陈丽

关键词 ：机械通气, 肺纤维化, Ⅲ型前胶原蛋白, 半胱氨酰白三烯, 结缔组织生长因子, 新生大鼠

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］

Key words： Mechanical ventilation Lung fibrosis ProcollagenⅢ Cysteinyl leukotriene Connective tissue growth factor Neonatal rats

PACS:

R-33

引用本文:

黄进洁,吴本清,丁璐等. 不同潮气量通气启动新生鼠肺纤维化的特点[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.

链接本文:

http://www.zgddek.com/CN/ 或 http://www.zgddek.com/CN/Y2010/V12/I10/799

	［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.
	［12］花少栋，杜江，刘秀香，唐雯,杨丽华,封志纯.新生兔机械通气并氧吸入肺损伤的实验研究［J］.实用儿科临床杂志，2007， 22（2）：133-157.
	［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.
	［17］富建华,薛辛东.高氧诱导早产鼠肺纤维化中结缔组织生长因子的表达及其意义［J］.中国当代儿科杂志，2007，9（5）：449-452.
	［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.
	［20］樊麦英，肖奇明.白三烯制剂对大鼠急性肺损伤的干预作用［J］.基础研究，2007， 4(19)：127-128.
	［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.