孕鼠甲状腺激素水平对胎鼠心肌细胞凋亡的影响研究  

Effects of maternal thyroid hormone level on the apoptosis of fetal cardiomyocytes in rats

作　　者：范稣圳 陶波[1] 刘浙波 崔胜宇 徐林[1] FAN Suzhen;TAO Bo;LIU Zhebo;CUI Shengyu;XU Lin(Department of Cardiology,Institute of Cardiovascular Diseases of Wuhan University/Hubei Key Laboratory of Cardiovascular Diseases/People′s Hospital of Wuhan University,Wuhan,Hubei 430060,China)

机构地区：[1]武汉大学心血管病研究所/心血管病湖北省重点实验室/武汉大学人民医院心内科,武汉430060

出　　处：《重庆医学》2020年第7期1036-1041,共6页Chongqing medicine

摘　　要：目的探讨妊娠期母体甲状腺激素(TH)水平异常对子代心脏损伤的作用及可能的机制。方法12只SD雌鼠分为对照组、左甲状腺素(L-T4)组、丙硫氧嘧啶(PTU)组。与雄鼠合笼后,L-T4和PTU分别添加于孕鼠饮水中。收集各组孕鼠血清,ELISA法测定孕鼠血甲状腺素(T4)和三碘甲腺原氨酸(T3)水平。记录胎鼠体质量,心、肾质量。各组胎鼠心脏通过HE染色和醋酸铀-枸橼酸铅染色观察其形态学和超微结构的改变,采用TUNEL法评估其心肌细胞凋亡水平,Western blot法检测心肌组织Bcl-2、Bax、胱天蛋白酶(caspase)-3、caspase-8、caspase-9水平及细胞质细胞色素c(Cyt-c)、凋亡诱导因子(AIF)等线粒体途径介导凋亡相关因子的水平。结果各组孕鼠未见畸形胎和死胎。与对照组相比,L-T4组孕鼠血清T4、T3水平增高,PTU组孕鼠血清T4、T3水平降低,差异有统计学意义(P<0.05)。与对照组比较,L-T4组、PTU组胎鼠心肌组织可见形态学和超微结构改变,TUNEL染色阳性面积和强度增加,Bax、caspase-3、caspase-8、caspase-9表达及细胞质Cyt-c、AIF水平增高,Bcl-2表达降低,差异有统计学意义(P<0.05)。结论孕鼠TH水平的过高或过低均会增加胎鼠心肌细胞凋亡,且与心肌细胞线粒体损伤有一定关系。Objective To investigate the effects of abnormal maternal thyroid hormone(TH)level during pregnancy on cardiac injury of fetal rats and the underlying mechanisms.Methods Twelve Sprague-Dawley(SD)female rats were divided into the control group,the L-thyroxin(L-T4)group.the propylthiouracil(PTU)group.L-T4 and PTU were added in drinking water for pregnant rats after mating,respectively.Serum of pregnant rats was collected from each group.The serum TH(T4)and triiodothyronine(T3)were determined by enzyme linked immunosorbent assay(ELISA).Body weight,heart weight and kidney weight were measured in fetal rats.The morphological and ultrastructural changes of fetal rats`heart were observed by hematoxylin-eosin(HE)staining and uranyl acetate-lead citrate staining.The apoptosis of cardiomyocytes was observed by TdT mediated dUTP nick end labeling(TUNEL).The levels of Bcl-2,Bax,caspase-3,caspase-8,caspase-9 in myocardial tissue and cytoplasmic cytochrome c(Cyt-c),apoptosis-inducing factor(AIF)in cytoplasm,which were related to mitochondrial pathway-mediated apoptosis,were detected by Western Blot.Results No deformed fetus and stillbirth were observed.Compared with the control group,serum T4 and T3 levels increased in the L-T4 group and decreased in the PTU group(P<0.05).Compared with the control group,morphological and ultrastructural changes were observed in myocardial tissue of fetal rat in the L-T4 group and the PTU group,the positive area and intensity of TUNEL staining increased.And the expressions of Bax,caspase-3,caspase-8,caspase-9,cytoplasmic Cyt-c and AIF increased,and the expressions of Bcl-2 decreased,with statistically significant differences(P<0.05).Conclusion High or low level of maternal thyroid hormone may cause the increase of cardiomyocytes apoptosis in fetal rats,and has a certain correlation with mitochondrial of cardiomyocytes.

关 键 词：甲状腺激素 细胞凋亡 妊娠期甲状腺功能异常 子代心肌细胞 

分 类 号：R541.1[医药卫生—心血管疾病]