Xu Chang, Chen Zhong-Xian, Liu Wen-Ying, Wang Yuan-Xiang, Xiong Zhong-Xun
Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Zhonghua Wai Ke Za Zhi. 2009 Feb 15;47(4):301-4.
To access the expression of transforming growth factor beta1 (TGF-beta1) in the lung of Nitrofen-induced congenital diaphragmatic hernia rat model.
Twelve timed-pregnant Sprague-Dawley rats were randomly divided into two groups, namely control group and CDH group on day 9.5 of gestation. Each rat in the CDH group was given 125 mg of Nitrofen (dissolved in seed fat) by gavage. Each rat in the control group was given the same dose of single oil. On day 16 of gestation, the two groups mentioned above were divided into three subgroups, and fetuses were delivered by cesarean section respectively on day 16, 18 and 21 of gestation. After the fetuses were checked for diaphragmatic hernia, lung tissue weight (LW) and body weight (BW) of each fetus on gestational day 21 were recorded. Lung histologic evaluations were made with microscope and TGF-beta1 immunohistochemistry staining were performed with image analyzing.
At day 16 of gestation, no visible diaphragm closure was observed in all fetuses. Diaphragmatic hernia was observed in 32 of the 44 rat fetuses of the CDH groups on day 18 and day 21 of gestation (72.7%). Lw/Bw of the 21d subgroups of CDH group were lower than those of corresponding control group (P < 0.01). Observed under the microscope, the lungs of fetuses in CDH groups showed marked hypoplasia. The expression of TGF-beta1 was detected in cytoplasmic, without definite expression in nuclear. It was significantly stronger that the expression of TGF-beta1 was in the lungs of the CDH group than that of the control group (P < 0.01).
Nitrofen interferes with lung development in early stage of the fetal before the diaphragm developed. TGF-beta1 would be one of the important factors which lead to pulmonary hypoplasia.
探讨转化生长因子β1(TGF-β1)在硝呋烯腙诱导的先天性膈疝大鼠模型肺组织中的表达情况。
选取12只孕龄合适的Sprague-Dawley大鼠,于妊娠第9.5天随机分为两组,即对照组和先天性膈疝(CDH)组。CDH组每只大鼠经口灌胃给予125 mg硝呋烯腙(溶于种子油)。对照组每只大鼠给予相同剂量的单纯油剂。妊娠第16天,上述两组再各自分为三个亚组,分别于妊娠第16、18和21天通过剖宫产取出胎儿。检查胎儿有无膈疝后,记录妊娠第21天各胎儿的肺组织重量(LW)和体重(BW)。用显微镜进行肺组织学评估,并用图像分析进行TGF-β1免疫组化染色。
妊娠第16天,所有胎儿均未观察到明显的膈肌闭合。妊娠第18天和第21天,CDH组44只大鼠胎儿中有32只出现膈疝(72.7%)。CDH组21天亚组的LW/BW低于相应对照组(P<0.01)。显微镜下观察,CDH组胎儿肺表现为明显发育不全。TGF-β1在细胞质中表达,细胞核中无明确表达。CDH组肺组织中TGF-β1的表达明显强于对照组(P<0.01)。
硝呋烯腙在膈肌发育之前干扰胎儿早期肺发育。TGF-β1可能是导致肺发育不全的重要因素之一。