CAJ | 학술논문

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 GA-TA4、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。
목적탐토협산대고혈당잉서자대심장발육상관단백GATA4、Nkx2.5표체적영향。방법장수잉적40지SD대서수궤균분위5조：정상대조조、모형조、협산제3천조(FA3rd조)、협산제7천조( FA7th 조)、협산제15천조(FA15th조)；학인수잉후,제정상대조조외,기타4개조일차성안38 mg/kg여복강주사련뇨좌균소( STZ)복제고혈당잉서모형,기중FA3rd조、FA7th조、FA15th조3개간예조분별종잉제3、7、15천개시,매천여협산0.8 mg/kg관위지임신결속。재잉서잉21 d시취자서심장,HE염색관찰자서심기；면역조화법급Western blot법검측자서심장발육상관기인GATA4、Nkx2.5적단백표체。결과 STZ간예후잉서혈당명현승고(P<0．05),부분자서심기가견손상；면역조화현시, GATA4단백재심방、심실、실간격、판막균유표체；Nkx2.5단백재심방、심실、실간격균유표체,단재판막미견명현표체；Western blot현시,여정상대조조비교,STZ간예조GATA4급Nkx2.5단백표체균하조(P<0．05),FA3rd조급FA7th조적단백표체수평균현저고우모형조(P<0．05),차FA3rd조적단백상조정도고우FA7th조(P<0．05),FA15th조여모형조적단백표체수평차이무통계학의의。결론잉서적고혈당상태가사자대심장손상급심장발육상관단백GATA4、Nkx2．5표체수평하조；급시보충협산가상조 GA-TA4、Nkx2.5단백표체수평,대처우모체고혈당상태영향하적자서심장적발육가능구유보호작용。
Objective To investigate the effects of oral folic acid supplementation on the expressions of heart devel-opment-related proteins GATA4 and Nkx2 . 5 of offspring in the rat models of maternal hyperglycemia during preg-nancy. 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, interven-tricular 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 de-creased in the groups intervened by streptozotocin compared with the control group(P<0. 05). The expression lev-els 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 de-velopment-related protein GATA4 and Nkx2. 5 at the same time. Folic acid supplementation may increase the ex-pressions of GATA4 and Nkx2. 5 protein and has a protective effect on offspring’s myocardial development of mater-nal hyperglycemia in pregnancy.