不同潮气量通气启动新生鼠肺纤维化的特点

Lung fibrosis induced by mechanical ventilation with different tidal volume in neonatal rats

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］

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］