叶酸对高血糖孕鼠子代心脏发育相关蛋白表达的影响  

Influence of folic acid on heart development-related proteins in offspring of maternal hyperglycemia rats during pregnancy

作　　者：詹一科[1] 仇小强[2] 马若嘉 

机构地区：[1]桂林医学院附属医院心血管内科,桂林541001 [2]广西医科大学公共卫生学院,南宁530021

出　　处：《安徽医科大学学报》2014年第7期905-909,共5页Acta Universitatis Medicinalis Anhui

基　　金：广西自然科学基金重点项目(编号:2010GXNSFD013054)

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40只SD大鼠随机均分为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38 mg/kg予腹腔注射链脲佐菌素(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0.8 mg/kg灌胃至妊娠结束。在孕鼠孕21 d时取子鼠心脏,HE染色观察子鼠心肌;免疫组化法及Western blot法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(P<0.05),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(P<0.05),FA3rd组及FA7th组的蛋白表达水平均显著高于模型组(P<0.05),且FA3rd组的蛋白上调程度高于FA7th组(P<0.05),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。Objective To investigate the effects of oral folic acid supplementation on the expressions of heart development-related proteins GATA4 and Nkx2 . 5 of offspring in the rat models of maternal hyperglycemia during pregnancy. Methods Forty Sprague-Dawly（ SD） rats in pregnancy were randomly divided into 5 groups：control group, models group, FA3rd group, FA7th group and FA15th group. Except for the control group, maternal hyperglycemi-a was induced by a single intraperitoneal injection of streptozotocin （38 mg/kg） in SD rats of four other groups on the first day of pregnancy. And group FA3rd, FA7th, FA15th were intragastriced with folic acid （0. 8 mg/kg per day） from day 3,7,and 15 of pregnancy respectively until the end of the pregnancy. The hearts of neonates were taken on the 21st day of pregnancy and the heart tissues with haematoxylin and eosin staining were observed. The expressions of GATA4 and Nkx2. 5 proteins were detected by immunohistochemistry and Western blot. Results The blood glucose level of pregant rats intervened by streptozotocin was significantly increased（P〈0. 05）,and in a part of their offspring,the cardiac injury was detected. GATA4 protein was expressed in atria,ventricles, interventricular septum and valvular tissues. Nkx2. 5 protein was expressed in atria, ventricles and interventricular septum, while it was not expressed obviously in valvular tissues. The expression levels of GATA4 and Nkx2. 5 were decreased in the groups intervened by streptozotocin compared with the control group（P〈0. 05）. The expression levels of GATA4 and Nkx2. 5 in FA3rd group and FA7th group were higher than that of the models group（P〈0. 05）. Compared with FA7th group, the expression of GATA4 and Nkx2. 5 in FA3rd group increased greatly（P〈0. 05）. However, it showed no significant difference between the models group and FA15th group. Conclusion Maternal hyperglycemia during pregnancy may result in offspring’ s cardiac injury and decrease their expressions of heart development-rela

关 键 词：叶酸 心脏发育 子代 母体高血糖 

分 类 号：R725.4[医药卫生—儿科]