叶酸对高血糖孕鼠子代心脏发育相关基因蛋白表达的影响

发布时间：2018-07-26 15:36

【摘要】：目的：探讨叶酸对高血糖孕鼠子代心脏发育相关蛋白GATA4、Nkx2.5表达的影响。方法：将受孕的SD大鼠40只随机均分为5组：正常对照组、模型组、叶酸第3天组（FA3rd组）、叶酸第7天组（FA7th组）、叶酸第15天组（FA15th组）；确认受孕后，除正常对照组外，其他4个组一次性按38mg/kg予腹腔注射链脲佐菌素（streptozotocin, STZ）复制高血糖孕鼠模型，，其中FA3rd组、FA7th组、FA15th组3个干预组分别从孕第3、7、15天开始，每天予叶酸0.8mg/kg灌胃至妊娠结束。在孕鼠孕21d时取子鼠心脏，HE染色观察子鼠心肌；免疫组化（Immunohistochemistry）及蛋白免疫印迹（Western blot）检测子鼠心脏发育相关基因GATA4、Nkx2.5的蛋白表达。结果：STZ干预后孕鼠血糖明显升高（P0.05），部分子鼠心肌可见损伤；免疫组化显示，GATA4蛋白在心房、心室、室间隔、瓣膜均有表达；Nkx2.5蛋白在心房、心室、室间隔均有表达，但在瓣膜未见明显表达；Western blot显示，与正常对照组比较，STZ干预组GATA4及Nkx2.5蛋白表达均下调（P0.05），FA3rd组及FA7th组的蛋白表达水平均显著高于模型组（P0.05），且FA3rd组的蛋白上调程度高于FA7th组（P0.05），FA15th组与模型组的蛋白表达水平差异无统计学意义。结论：孕鼠的高血糖状态可使子代心脏损伤及心脏发育相关蛋白GATA4、Nkx2.5表达水平下调；及时补充叶酸可上调GATA4、Nkx2.5蛋白表达水平，对处于母体高血糖状态影响下的子鼠心脏的发育可能具有保护作用。
[Abstract]:Aim: to investigate the effect of folic acid on the expression of cardiac development-associated protein GATA4 and Nkx2.5 in the offspring of hyperglycemic pregnant rats. Methods: forty pregnant SD rats were randomly divided into 5 groups: normal control group, model group, folic acid 3rd day group (FA3rd group), folic acid 7th day group (FA7th group), folic acid 15th day group (FA15th group). The other four groups were injected intraperitoneally with streptozotocin (38mg/kg) to induce hyperglycemia in pregnant rats. The rats in FA3rd group were given folic acid 0.8mg/kg daily until the end of pregnancy, respectively, from the 3rd day of gestation to the end of pregnancy in three intervention groups (FA3rd group, FA7 th group and FA15 th group). At the 21st day of gestation, the neonatal rat heart was stained with HE, and the expression of GATA4Nkx2.5 was detected by immunohistochemical (Immunohistochemistry) and Western blot (Western blot). Results the blood glucose of pregnant rats increased significantly (P0.05), and the myocardial damage was observed in some of the offspring. Immunohistochemical staining showed that GATA4 protein was expressed in atrial, ventricular, ventricular septum and valvular septum, and Nkx2.5 protein was expressed in atrium, ventricle and interventricular septum. However, there was no obvious expression of Western blot in valvular valve. Compared with the normal control group, the protein expression of GATA4 and Nkx2.5 in the STZ-treated group was significantly lower than that in the model group (P0.05). The protein expression level in the FA3rd group was significantly higher than that in the model group (P0.05), and the protein expression level in the FA3rd group was higher than that in the FA7th group (P0.05) and the model group (P0.05). The difference was not statistically significant. Conclusion: the hyperglycemia of pregnant rats can down-regulate the expression of GATA4Nkx2.5, and timely supplementation of folic acid can up-regulate the expression of GATA4Nkx2.5 protein. It may have protective effect on the heart development of the offspring under the influence of maternal hyperglycemia.
【学位授予单位】：桂林医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R714.256

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