Research About The Relationship Between MTOR Signalling And The Fetal Lung Development From GDM Mice

Research BackgroundGestational diabetes(Geastational diabetes mellitus, GDM) refers to appear during pregnancy or first diagnosed with varying degrees of impaired glucose tolerance(does not include gestational diabetes mellitus). Maternal glucose metabolism is out of imbalance, so that the fetus in utero exposure to high glucose and high insulin environment, thus affecting the development of fetal organs, especially the fetal lung development [1-4]. In clinically, gestational diabetes complications, for pregnant women, there may be too much amniotic fluid and prone to diabetic ketoacidosis; it can cause fetal macrosomia or intrauterine growth restriction, miscarriage, premature birth, even fetal malformation; Related to infant,it leads to neonatal respiratory distress syndrome(RDS) and neonatal hypoglycemia [5,6]. RDS is a direct manifestation of fetal lung maturation disorders in GDM, delayed fetal lung development,the synthesis and secretion s of surfactant protein in type ?pneumocytereduces, resulting in pulmonary surfactant function is blocked, it can not effectively reduce the surface tension of the lungs, neonatesuffers difficult breathing,when treatment is not timely, RDS occurs[7].While the molecular mechanism ahout decreased expression of surfactant protein on GDM fetal lung is unclear.mTOR, mammalian target of Rapamycin, also known as mammalian target of rapamycin, It is a serine / threonine protein kinase,works as the center of a variety of intracellular regulatory molecules physiological activities, accepts and integrates a variety of intracellular and extracellular stimulus, such as high sugar and high insulin were able to induce phosphorylation ofit(p-mTOR)(ser2448, Note: in our experiment, the phosphorylation site of mTOR isser2448 site), cause changes in downstream factors [8,9]. Under physiological conditions, expression of p-mTOR in the third trimester fetal lung tissue is very low [10], when mTOR in hyperphosphorylation inhibites production of surfactant protein [11,12]. Additionally, mTOR can contact the development of trachea and blood vessels concertedly [13].Thus, the purpose of this study is to explore the expression of p-mTOR in fetal lung tissue from GDM,whether involved in fetal immature lung of gestational diabetes, and specific mechanisms.Todisclosed mTOR's role in fetal lung development in Gestational diabetes,andprovide new therapeutic target for the treatment of disorders of fetal lung maturity.?purpose?To explore whether mTOR have a role inin the lung of fetus from GDM mice and the may mechanisms.?method?1.In the SPF animal experiment center,30 pregnant SD rats were randomly divided into experimental group(diabetic group), the intervention group(on the basis of diabetic model, giving rapamycin) and control group(citrate buffer);2. ELISA assay to dectet insulin fetal serum and insulin in the amniotic fluid3. Light microscopy to dectet fetal lung morphology4. Immunohistochemistry and immunofluorescence to detect the expression of SP-B and SP-C in fetal lung tissue5. Western Blot to detect the protein expression levels of mTOR, P-mTOR, SP-B, SP-C in fetal lung tissue6. RT-PCR technique to detect them RNAs expression of SP-B, SP-C in fetallung tissue.?result?1. Successfully constructed 20 gestational diabetes in pregnant rats;2. After applying mTOR inhibitor, the expression of p-mTOR in fetal lung was significantly reduced compared with diabetic group, theintervention succeed;3.4 in abortion,the diabetic group and the intervention group each miscarriage 2, 8 in diabetic group, 8 in intervention group and 10 in control group;4. Fetal blood glucose and serum insulin levels in diabetic group and intervention group were higher than normal group;5. the control group, expression of p-mTOR in diabetes group was abnormally high, SP-B, SP-C levels were significantly decreased; while comparing with diabetic group, p-mTOR expression level in the intervention group decreased significantly, SPB, SPC levels increased significantly;6. Fetal lung in general structure, the control group,well developed lung, alveolar space islarge,the number of pulmonary alveoli is moderate, thin alveolar septa; structural development of the diabetic fetal lung is poor, small alveolar space with alarger number,alveolar septa is thick; poor lung development in the intervention group, similar to the general structure of the diabetic group.? conclusion?Abnormal activation of mTOR signaling contributes the disorders infetal lung maturation from GDM mice.