小潮气量常规机械通气对发育肺生长因子和炎症因子表达的影响

Effects of conventional mechanical ventilation with low tidal volume on the expression of growth factors and inflammatory mediators in developing porcine lungs

目的探讨小潮气量常规机械通气对发育肺生长因子（GFs）和炎症因子表达的影响。方法分别将早产猪（85％孕龄）、足月新生猪及幼猪（4-5周龄）随机分为机械通气组（MV组）和自主呼吸对照组（NMV组）。调节呼吸机参数，使呼出气潮气量维持在6～8mL／kg，机械通气6h（早产猪）或24h（新生猪、幼猪）后检测肺组织GFs（PDGF-B，IGF-Ⅰ，KGF，HGF，VEGF，TGF-β1）及炎症因子（IL-1β，IL-6，IL-8，TNF-α）mRNA表达，免疫组化方法观察GFs蛋白表达与分布。多组间比较用单因素方差分析或Kruskal-Wallis检验，两组间比较用t检验或Mann-Whitney U检验。结果①在早产组，MV组PDGF-B，IL-1β，IL-6，IL-8 mRNA水平较NMV组增高（5．11±0.10vs4.88±0.01，4.95±0.27vs4．08±0.37，4.76±0.27vs4.00±0.28，5.31±0．57vs4．15±0.46；P〈0．01或0．05），IGF-Ⅰ mRNA水平降低（3.54±0．13vs3．80±0.11；P〈0.01）；②在足月新生组及幼年组，MV组GFs及炎症因子mRNA水平较NMV组差异均无显著性。结论生后早期机械通气干扰了早产肺GFs的表达，并诱发促炎因子表达，促进了肺损伤的发生；但对足月和幼年肺GFs和炎症因子表达无明显影响。

Objective To study the effects of conventional mechanical ventilation （CMV） with low tidal volume on developmental porcine lungs by examining the expression of growth factors and inflammatory mediators. Methods Twelve preterm piglets born at 99 days of gestational age, 12 term neonatal piglets and ll young piglets （ 4-5-weeks old） were randomly placed on CMV or were not ventilated （ control group）. The ventilator settings were adjusted to provide a tidal volume of 6-8 mL/kg in order to maintain a normal blood-gas value. After 6 hrs （ preterm piglets） or 24 hrs （ neonatal and young piglets） of mechanical ventilation, the mRNA expression of growth factors PDCF-B, ICF-Ⅰ, KCF, HCF, VECF and TGF-β1 and proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α in the lung tissue was measured using RT-PCR. Growth factor protein expression was measured with immunohistoehemistry. Results In preterm piglets, the CMV group had increased mRNA expression of PDGF-B （5.11 ± 0. 10 vs 4.88±0.01 ）, IL-1β （4.95±0.27 vs 4.08±0. 37 ）, IL-6 （4.76±0.27 vs 4.00±0.28） and IL-8 （5.31±0.57 vs 4.15±0.46）, but decreased IGF-Ⅰ mRNA expression （3.54 ± 0. 13 vs 3.80 ±0. 11 ） compared with those in the control group （P 〈0.05 or 0.01 ）. In term neonatal piglets and young piglets, there were no significant differences in the mRNA expression of growth factors and proinflammatory cytokines between the CMV and control groups. Conclusions CMV caused inflammatory injury in immature lungs by increasing the expression of proinflammatory cytokines and PDGF-B and decreasing IGF-Ⅰ expression. However, CMV had no effects on pulmonary expression of growth factors and inflammatory mediators in term neonatal piglets and young piglets.