Effects of Tetrandrine Prenatal Intervention on Alveolar Epithelial Cells Type Ⅰ Differentiation in Rat Model of Nitrofen-induced Congenital Diaphragmatic Hernia

XIAO Bin, XU Chang, LIU Min. et al

Abstract

To investigate the effects of Tetrandrine（TET） prenatal intervention on the differentiation of alveolar epithelial cells type Ⅰ (AECⅠ) in rat model of Nitrofen-induced congenital diaphragmatic hernia（CDH）. Methods Timed-pregnant Sprague-Dawley rats were divided into three groups, namely control， CDH and TET group on day 9.5 of gestation. The rats in TET group and CDH group were given 125 mg of Nitrofen by gavage one time, while the rats in control group were given the same dose of seed fat. After that, the rats in TET group was given 30 mg/kg of TET by gavage once a day for three days from day 18.5 of gestation, while the rats in CDH and control group were given the same dose of normal saline. On day 21.5 of gestation, all fetuses were delivered by cesarean, the lungs of fetuses were histologically evaluated by microscope and electron microscope. The expressions of type Ⅰ cell-specific protein（RT140） and thyroid transcription factor 1（TTF1） in alveolar fluid content were analyzed by RT-PCR and immunohistochemistry staining. To detect the number of AECⅠand AECⅡof each group by transmission electron microscopy and calculate the percentage of AEC Ⅰ and AEC Ⅱ(Ⅰ/Ⅱ %). Results The microscope and electron microscope study found the lungs of fetuses in CDH group showed marked hypoplasia, in contrast to the improvement of hypoplasia in TET fetuses. The pulmonary alveolar area had significant difference statistically （ P<0.01） in each group, which present as control>TET>CDH. Ⅰ /Ⅱ % had significant difference statistically （ P<0.01） in each group, which present as control>TET>CDH. The expression level of TTF1 was up-regulated in both CDH and TET groups, and it was higher in CDH group （ P<0.01）.The expression level of RT140 were down-regulated in CDH and TET groups, which was lower in CDH group（ P<0.01）. Conclusion The development of AECⅠwas interfered in CDH rat model, TET prenatal treatment could improve the lung development of CDH.

 

Keywords:  Congenital diaphragmatic hernia, Lung development, Alveolar epithelial cells type Ⅰ 

 

Full Text:

PDF


References


Hedrick HL. Management of prenatally diagnosed congenital diaphragmatic hernia. Semin Pediatr Surg, 2013 ; 22 (1): 37-43.

Van den Hout L, Schaible T, Cohen-Overbeek ТЕ. et al. Actual outcome in infants with congenital diaphragmatic hernia; the role of a standardized postnatal treatment protocol. Fetal Diagn Ther.2011;29( 1) :55-63.

Badillo A. Gingalewski C. Congenital diaphragmatic hernia: treatment and outcomes. Semin Perinatal,2014;38(2) :92-96.

Van Tuyl M, Blommaart PJ, Keijzer R, et al. Pulmonary surfactant protein A, B« and С mRNA and protein expression in the nitrofen-induced congenital diaphragmatic hernia rat model. Pediatr Res,2003 ; 54(5); 641-652.

Takayasu H, Nakazawa N, Montedonico S, et al. Impaired alveolar epithelial cell differentiation in the hypoplastic lung in nitrofen-induced congenital diaphragmatic hernia. Pediatr Surg Int,2007;23(5);405-410.

Morrisey EE, Hogan BL. Preparing for the first breath; genetic and cellular mechanisms in lung development. Dev Cell. 2010;18(1) :8-23.

Liu W, Feng J, Jia H, et al. Effect of prenatal tetrandrine therapy on pulmonary vascular structural remodeling in the nitrofen-induced CDH rat model. Chin Med J (Engl) ,2000; 113 (9) ;813-816.

Lin H, Wang Y. Xiong Z, et al. Effect of antenatal tetrandrine administration on endothelin-1 and epidermal growth factor levels in the lungs of rats with experimental diaphragmatic hernia. J Pediatr Surg.2007;42( 10) : 1644-1651.

Williams MC. Alveolar type I cells; molecular phenotype and development. Annu Rev Physiol, 2003; 65; 669-695. doi; 10.1146/annurev. physiol. 65.092101. 142446.

Sugimoto K. Takayasu H. Nakazawa N, et al. Prenatal treatment with retinoic acid accelerates type 1 alveolar cell proliferation of the hypoplastic lung in the nitrofen model of congenital diaphragmatic hernia. J Pediatr Surg, 2008; 43 ( 2 ): 367-372.

Johnston LC, Gonzales LW, Light foot RT, et al. Opposing regulation of human alveolar type || cell differentiation by nitric oxide and hyperoxia. Pediatr Res,2010;67(5) ;521-525.

Brownfoot FC, Gagliardi DI, Bain E, et al. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev, 2013; 8: CD006764. doi: 10. 1002/14651858. CD006764. pub3.

Schmidt AF, Gonsalves FL, Regis AC, et al. Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat. Am J Obstet Gynecol, 2012; 207 (1) ;76. e25-32.

Liu B, Wang T, Qian X, et al. Anticancer effect of tetrandrine on primary cancer cells isolated from ascites and pleural fluids. Cancer Lett,2008; 268( 1): 166-175.


Refbacks

  • There are currently no refbacks.