支气管肺发育不良患儿产后及不同机械通气时段血浆β-联蛋白、转化生长因子β1、Clara细胞分泌蛋白、Ⅱ型肺泡细胞表面抗原水平变化的意义

Significance of plasma β-catenin, transforming growth factor-β1, Clara cell secretion protein, Krebs yon den Lungen-6 level changes of bronchopulmonary dysplasia premature children after birth and in different mechanical ventilation period

目的动态监测支气管肺发育不良（BPD）患儿产后及不同机械通气时段血浆β-联蛋白、Ⅱ型肺泡细胞表面抗原（KL-6）、Clara细胞分泌蛋白（CC16）、转化生长因子β1（TGF—β1）水平的变化，探讨其在机械通气肺损伤中的作用及BPD发生的高危因素。方法将90例早产儿分为早产非机械通气组、机械通气非BPD组和机械通气BPD组，每组30例；另选择足月健康新生儿40例作为健康对照组。酶联免疫吸附试验法检测四组通气前，通气后1，24，48，72h及撤机后24h血浆β-联蛋白、KL-6、CC16、TGF-β1水平。结果健康对照组、早产非机械通气组、机械通气非BPD组、机械通气BPD组胎龄和出生体质量[（40．50±1．46）、（33．07±2．42）、（31．67±2．73）、（29．80±1．71）周和（3184．33±548．99）、（1752．33±255．81）、（1433．00±177．30）、（1254．50±117．78）g]逐渐降低，两两比较差异均有统计学意义（P〈0．05）；机械通气βPD组机械通气时间和吸氧时间均明显长于机械通气非BPD组[（15．23±4．28）d比（3．53±1．01）d和（45．57±7．89）d比（18．57±3．93）d]，差异有统计学意义（P〈0．05）。健康对照组、早产非机械通气组、机械通气非βPD组、机械通气BPD组血浆β-联蛋白和TGFβ1逐渐升高，血浆CC16逐渐降低，两两比较差异有统计学意义（P〈0．05）。四组血浆Kb6比较差异无统计学意义（P〉0．05）。机械通气βPD组多数机械通气时段血浆KL-6、CC16、TGF-β1、β-联蛋白均差于机械通气非βPD组。β-联蛋白与TGF-β1、KL-6有相关性（r=0．374，0．418，P〈0．01）。多元逐步回归分析结果显示，低出生体质量、机械通气时间延长、产后高血浆TGF-β1、β-联蛋白及低血浆CC16为βPD发生的高危因素（P〈0．01或〈0．05）。结论产后高血浆β-联蛋白、TGF—β1及低血浆CC16可能与βPD的发生密切相关，β-联蛋白、KL-6、TGF—β1在BPD的发生和发展中互为因果关系。动态监测机械通气早产儿血浆β-联蛋白、KL-6、CC16、TGF-β1水平，有助于监测机械通气肺损伤的发生，对BPD早期诊断、治疗及预后评估具有重要的临床指导价值。

Objective To dynamically monitor the changes of plasma β-catenin,transforming growth factor-β1（TGF-β1）, Clara cell secretion protein（CC16）, Krebs yon den Lungen-6 （KL-6） level of bronchopulmonary dysplasia （BPD） premature children after birth and in different mechanical ventilation period, so as to discuss the function in ventilator-induced lung injury and explore the risk factors of BPD. Methods Ninety premature children were divided into non-mechanical ventilation group,non-BPD mechanical ventilation group, BPD mechanical ventilation group and 30 cases in each group. Besides, another 40 normal term infants to make comparison were selected as control group. The levels of plasma β -catenin, KL-6, CC 16, TGF-β 1 were measured by enzyme-linked immunosorbent assay before mechanical ventilation and 1,24,48,72 h after mechanical ventilation and 24 h after weaning. Results C, estational age and birth weight decreased in control group, non-mechanical ventilation group, non-BPD mechanical ventilation group, BPD mechanical ventilation group [ （40.50 ± 1.46 ）, （ 33.07 ± 2.42 ）, （ 31.67 ± 2.73 ）, （29.80 ± 1.71 ） weeks and （3 184.33 ± 548.99）, （1 752.33 ± 255.81 ）, （1 433.00 ± 177.30）, （1 254.50 ± 117.78） g ], pairwise comparisons were statistically significant differences （P 〈 0.05）. The time of mechanical ventilation and oxygen inhalation in BPD mechanical ventilation group was longer than that in non-BPD mechanical ventilation group[（15.23 ±4.28） d vs. （3.53 ± 1.01） d and （45.57 ±7.89） d vs. （18.57 ±3.93） d],and there was significant difference （P 〈 0.05）. The level of plasma β -catenin, TGF-β1 was increased and the level of plasma CC 16 was decreased in control group, non-mechanical ventilation group, non-BPD mechanical ventilation group,BPD mechanical ventilation group,pairwise comparisons were statistically significant differences （P 〈 0.05 ）. There was no significant difference in the level of plasma KL-6 among four groups （P 〉 0.05 ）. The level of plasma KL-6, CC16,TGF-β1, β-catenin in BPD mechanical ventilation group at mostly period was worse than that in non-BPD mechanical ventilation group. In BPD mechanical ventilation group, the level of plasma β -catenin directly correlated with TGF- β1,KL-6 （r = 0.374 and 0.418,P 〈 0.01）. Muhi-factor stepwise regression analysis indicated that the lower birth weight,longer mechanical ventilation, higher β -catenin, TGF- β1 after birth, lower CC 16 level were the risk factor of BPD （P 〈 0.01 or 〈 0.05）. Coulusions Higher plasma β-catenin,TGF-β1 and lower CC16 after birth have close relation with BPD, the level of plasma β -catenin, KL-6,TGF- β 1 in BPD development interact as both cause and effect. Dynamic detection of plasma β-catenin, TGF-β 1, KL-6 , CC 16 changes of mechanical ventilation in premature children will help monitor lung injury of mechanical ventilation, for the early diagnosis of BPD, treatment, and the evaluation of prognosis have important clinical value.