肺透明膜病早产儿尸检肺组织肺表面活性蛋白-C及Ki67的表达

Expression of surfactant protein-C and Ki67 in pulmonary tissues of premature infants died of hyaline membrane disease

目的探讨肺透明膜病（HMD）早产儿经机械通气／高氧或肺表面活性物质（PS）替代治疗后其尸检肺组织肺表面活性蛋白-C（SP—C）及增殖抗原Ki67表达情况，分析临床治疗与病理改变的关系。方法临床和病理确诊为HMD的早产儿，因HMD而在生后6h内接受机械通气及高浓度氧（FiO20．6～1．O）治疗无效死亡者30例。按接受机械通气／高氧治疗时间的长短，分1～3d、4～8d、9～16d和〉16d共4组，其中13例患儿同时接受了PS治疗。以无肺部疾病的5例早产儿为对照。应用免疫组织化学方法检测尸检肺组织标本中SP—C及Ki67的表达。多组间比较采用方差分析及q检验。结果机械通气／高氧治疗的HMD早产儿，其不同时期肺组织的病理表现符合HMD向支气管肺发育不良转变的病理特征。肺组织SP—C表达定位于Ⅱ型肺泡上皮细胞，Ki67表达主要定位于肺、支气管上皮细胞和肺成纤维细胞。机械通气／高氧治疗1～3d，SP—C及Ki67表达的平均光度值分别为0．1576±0．0327和0．1929±0．0403，较对照组（0．1891±0．0253、0．2297±0．0380）明显降低（P均〈0．05）；4d后，SP—C及Ki67表达均逐渐升高，至9～16d左右达高峰，分别为（O．2410±0．0225、0．2987±0．0116）。PS治疗组与无PS治疗组肺组织SP—C及Ki67表达差异无统计学意义（t值分别为2．007和0．458，P均〉0．05）。结论SP—C及Ki67表达改变参与了HMD早产儿机械通气／高氧治疗后肺组织的病理发展过程；PS治疗对SP—C及Ki67表达无明显影响。

Objective To determine the expression of surfactant protein-c （SP-C） and Ki67 in autopsy lung tissues of premature infants died of hyaline membrane disease （HMD） who were exposed to mechanical ventilation and high oxygen concentrations/pulmonary surfactant （PS）. The possible influence of surfactant on the expression of SP-C and Ki67 was also investigated. Methods Thirty preterm infants diagnosed as HMD by clinical data and pathology were selected. Mechanical ventilation and supplemental oxygen （FiO2 0.6-1.0） were given to these infants within 6 hours after birth. According to the duration of ventilation at high oxygen concentrations, all subjects were diveded into four groups： ventilation for 1-3 days, 4-8 days, 9-16 days and 〉16 days. Five premature infants died within 1 day after delivery for none pulmonary reasons served as controls. The expression of SP-C and Ki67 in lungs were detected by immunohistochemistry. Results The pulmonary pathology in these HMD infants at different phases was consisitent with the main features of different stages during the progress from HMD towards bronchopulmonary dysplasia. The positive staining of SP-C was restricted to type Ⅱ alveolar epithelial cells, and Ki67 positive were preferentially localized in nuclei of alveolar and bronchiolar epithelial cells and fibroblasts. Compared with the control group, the expression of SP-C and Ki67 in HMD infants decreased significantly after 1-3 days of ventialation, but increased after 4 days and reached the peak value after 9-16 days. The expression of SP-C and Ki67 in control group, 1-3 days and 9-16 days of ventialation were 0. 1891±0. 0253, 0. 1576±0. 0327 and 0.2271±0.0238 for SP-C and 0.2297±0.0380, 0.1929±0.0403 and 0.2849±0.0368 for Ki67, respectively. No significant difference in the expression of SP-C and Ki67 was found between infants treated with PS and those without （P〉0.05）. Conclusions SP-C and Ki67 may have participated in the pulmonary pathological process in ventilated/oxygen treated preterm infants with HMD, and exogenous surfaetant had no effect on the expression of SP-C and Ki67.