妊娠期糖尿病胎鼠肺发育与mTOR关系的研究  

Relationship between Lung Development and mTOR in Fetal Rats with Gestational Diabetes Mellitus

作　　者：宋婷 张青苗 欧阳为相[1] 柴新群[2] 邓飞涛[1] SONG Ting;ZHANG Qingmiao;OUYANG Weixiang;CHAI Xinqun;DENG Feitao(Department of Obstetrics and Gynecology,Union Hospital,Huazhong University of Science and Technology,Wuhan,430022,China;Department of Hepatobiliary Surgery,Union Hospital,Huazhong University of Science and Technology,Wuhan,430022,China)

机构地区：[1]华中科技大学附属协和医院妇产科,武汉市430022 [2]华中科技大学附属协和医院肝胆外科,武汉市430022

出　　处：《医学分子生物学杂志》2018年第5期289-294,共6页Journal of Medical Molecular Biology

基　　金：国家自然科学基金（No.30971072）

摘　　要：目的探讨妊娠期糖尿病胎鼠在宫内高血糖环境中，胎肺发育异常，其表面活性蛋白sP-B（surfactantprotein，SP-B）、SP-C（surfactantprotein，SP-C）的表达及与雷帕霉素靶蛋白mTOR（mammaliantargetofrapamycin，mTOR）及p-mTOR的相关性。方法妊娠大鼠分成实验组（糖尿病组），干预组（糖尿病模型＋雷帕霉素）及对照组（柠檬酸缓冲液）。光镜下观察各组孕21d胎肺组织的大体形态结构：通过免疫组化技术及Western印迹技术检测各组胎肺组织中p-mTOR、SP-B、SP-C的定位表达和蛋白表达水平；利用RT．PCR技术检测胎肺组织中sP-B、SP-C的mRNAs表达水平。结果与对照组相比，糖尿病组与干预组胎肺肺泡腔减小，数量增多，肺泡间隔明显增厚，胎肺结构发育差。免疫组化及Western印迹结果显示，与对照组相比，糖尿病组p-mTOR、mTOR在胎肺组织中的表达明显增加，sP-B、SP-C蛋白表达水平明显降低；而干预组各蛋白表达水平介于对照组和糖尿病组之间。RT-PCR结果显示，与对照组相比．GDM组胎肺组织中sP-B、sP-CmRNAs相对平均量显著性减少，而干预组中sP．B、SP-CmRNAs水平与GDM组相比显著性增加。结论妊娠期糖尿病胎鼠肺发育异常，表面活性蛋白sP-B、sP-c合成、分泌减少，可能与异常激活的mTOR表达增高有关。Objective Gestational diabetes mellitus fetus is exposed to intrauterine hyperglycemia, and fetal lung development is affected. Our objective is to investigate the abnormal expression of fetal lung structure in gestational diabetes mellitus, the expression of surface active protein SP-B and SP-C, and the correlation with mTOR and p-mTOR. Methods The rats were divided into ex- perimental group （diabetes group）, intervention group （diabetes model ＋ rapamyein） and con- trol group （citric acid buffer）o The gross morphological structure of fetal lung tissue was observed under light microscope for 21 days; The expression of p-roTOR, SP-B and SP-C in fetal lung tissue was detected by immunohistochemistry; The expression level of roTOR, p-roTOR, SP-B and SP-C protein in fetal lung tissue was detected by Western Blot technique, and the expression level of SP- B and SP-C in fetal lung tissue was detected by RT-PCR technique. Results Compared with the control group, the alveolar cavity decreased and the number increased, the alveolar septum thick- ened and the fetal lung structure poorly developed in the DM group and the intervention group. Immunohistochemieal and Western Blot results showed that, compared with the control group, the expression of p-roTOR and total roTOR in the fetal lung tissue was significantly increased in the diabetic group, and the expression level of SP-B and SP-C protein was significantly re- duced. The protein expression level of the intervention group was between the control group and thediabetes group. RT-PCR results showed that compared with the control group, the relative average of SP-B and SP-C mRNAs in the GDM group decreased significantly, while the level of SP-B and SP- C mRNAs in the intervention group was significantly higher than that in the GDM group. Conclusion Gestational diabetes mellitus is abnormal in fetal lung development. The decrease of SP-B and SP- C svnthesis and secretion mav be related to abnormal activation of mTOR.

关 键 词：妊娠期糖尿病 胎肺发育 MTOR P-MTOR SP-B SP-C 

分 类 号：R714.256[医药卫生—妇产科学]