【摘要】：目的：探討葉酸對(duì)高血糖孕鼠子代心臟發(fā)育相關(guān)蛋白GATA4、Nkx2.5表達(dá)的影響。方法：將受孕的SD大鼠40只隨機(jī)均分為5組：正常對(duì)照組、模型組、葉酸第3天組（FA3rd組）、葉酸第7天組（FA7th組）、葉酸第15天組（FA15th組）；確認(rèn)受孕后，除正常對(duì)照組外，其他4個(gè)組一次性按38mg/kg予腹腔注射鏈脲佐菌素（streptozotocin, STZ）復(fù)制高血糖孕鼠模型，，其中FA3rd組、FA7th組、FA15th組3個(gè)干預(yù)組分別從孕第3、7、15天開(kāi)始，每天予葉酸0.8mg/kg灌胃至妊娠結(jié)束。在孕鼠孕21d時(shí)取子鼠心臟，HE染色觀察子鼠心�。幻庖呓M化（Immunohistochemistry）及蛋白免疫印跡（Western blot）檢測(cè)子鼠心臟發(fā)育相關(guān)基因GATA4、Nkx2.5的蛋白表達(dá)。結(jié)果：STZ干預(yù)后孕鼠血糖明顯升高（P0.05），部分子鼠心肌可見(jiàn)損傷；免疫組化顯示，GATA4蛋白在心房、心室、室間隔、瓣膜均有表達(dá)；Nkx2.5蛋白在心房、心室、室間隔均有表達(dá)，但在瓣膜未見(jiàn)明顯表達(dá)；Western blot顯示，與正常對(duì)照組比較，STZ干預(yù)組GATA4及Nkx2.5蛋白表達(dá)均下調(diào)（P0.05），F(xiàn)A3rd組及FA7th組的蛋白表達(dá)水平均顯著高于模型組（P0.05），且FA3rd組的蛋白上調(diào)程度高于FA7th組（P0.05），F(xiàn)A15th組與模型組的蛋白表達(dá)水平差異無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論：孕鼠的高血糖狀態(tài)可使子代心臟損傷及心臟發(fā)育相關(guān)蛋白GATA4、Nkx2.5表達(dá)水平下調(diào)；及時(shí)補(bǔ)充葉酸可上調(diào)GATA4、Nkx2.5蛋白表達(dá)水平，對(duì)處于母體高血糖狀態(tài)影響下的子鼠心臟的發(fā)育可能具有保護(hù)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.
【學(xué)位授予單位】：桂林醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R714.256

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