孕鼠叶酸缺乏对新生大鼠肺发育及其表面活性蛋白C的影响

Effect of Folate Deficiency during Pregnancy on Lung Development and Surfactant Protein C in Neonatal Rats

目的寻找叶酸缺乏对大鼠肺发育影响的形态学证据,探讨肺表面活性蛋白C(SP-C)在孕鼠叶酸缺乏引起新生大鼠肺发育障碍中的作用。方法采用去叶酸RHAA配方饲料喂养大鼠,建立叶酸缺乏大鼠模型。叶酸缺乏组和对照组各18只大鼠,孕早期及孕晚期分别测定其血清叶酸水平;取各组出生14d新生大鼠右肺,常规石蜡包埋切片,用HE染色及免疫组织化学染色分别比较2组肺组织及SP-C阳性细胞的病理改变。结果叶酸缺乏组孕鼠孕早期及孕晚期血清叶酸水平均显著低于对照组(Pa<0.05),表明叶酸缺乏孕鼠模型建立成功。HE染色显示新生大鼠叶酸缺乏组肺组织结构明显被破坏;免疫组织化学染色显示,叶酸缺乏组与对照组比较,SP-C阳性的Ⅱ型细胞明显减少,黄色染色较淡,特异性显色区域较少。出生14d叶酸缺乏组新生大鼠SP-C阳性的Ⅱ型肺泡细胞免疫组织化学染色平均吸光度显著低于对照组(P<0.05)。结论孕期叶酸缺乏对新生大鼠肺发育造成一定影响,其机制可能是通过减少胎鼠肺组织SP-C的表达,进而影响肺表面活性物质的生成。

Objective To find morphological evidence that folate deficiency acts on lung development obstacles and abnormal lung functions,and explore the role of pulmonary surfactant protein C（SP-C）in lung development of folate deficiency rats.Methods By means of feding an amino acid-defined diet,rats model of folate deficiency were established.Thirty-six female Sprague-Dawley rats were divided into 2 equal groups：folate deficiency experimental group and control group.The serum folate levels were evaluated in early and late pregnant,respectively.On postnatal day 14,the right lung sections of rats were detected by HE and immunohistochemical staining in 2 groups.Results In early and late pregnant,the serum folate levels of folate deficiency experimental group were significantly lower than those of control group（Pa0.05）.HE staining of lung indicated that lung tissues were destructed obviously in folate deficiency experimental group.Immunohistochemical staining showed SP-C positive cells were significantly decreased and dyed light in folate deficiency rats compared with the controls.In type Ⅱ pneumocyte with SP-C positive,the average optical density was lower than that of control group（P0.05）.Conclusions Folate deficiency during pregnancy acts on lung development obstacles in rat off-springs.In lung tissue of rat fetus,reducing the SP-C expression and further decreasing the formation of pulmonary surfactant can be its mechanism.