大剂量硝酸甘油对大鼠母、胎心血管的影响

Effects of super dose nitroglycerin on fetal-maternal cardiovascular tissue in rat

目的:通过研究超大剂量硝酸甘油对大鼠母体、胎儿心血管组织诱生型一氧化氮合酶(iNOS)产生的影响,探讨其组织安全性。方法:给妊娠第7～17天之孕鼠口腔滴入硝酸甘油混悬液,每日1次,剂量分别为0.25 mg/kg体重、0.85 mg/lg体重,8.5mg/kg体重;另给生理盐水作为对照,4组每组15只鼠。妊娠足月后,分别取母、儿心脏、升主动脉,采用兔抗入iNOS单克隆抗体,免疫组织化学ABC法检测组织中iNOS的表达。结果;低剂量组(A组)及对照组母、儿心脏、大血管均未见iNOS染色.0.85 mg/kg体重组(B组)个别母鼠心脏内膜下肌层有iNOS表达,母鼠血管及仔鼠心脏、血管均未见iNOS表达,8.5mg/kg体重组(C组)母鼠心肌、血管平滑肌iNOS表达显著多于B组(P<0.05),仔鼠心脏、血管未见iNOS表达。结论:常规低剂量使用硝酸甘油对妊娠母体、胎儿心血管是安全的,而超量硝酸酸甘油在组织内可释放超量NO,发挥细胞毒作用.诱导iNOS表达,进一步引起细胞、组织的损伤。

Objective: To investigate the safety to fetus and maternal rats under super dose nitroglycerin through detecting the expression of inducible nitric oxide synthase (iNOS). Methods: Pregnant SD rats were treated with nitroglycerin once every day in 7th day to 17th day. The concentration of nitroglycerin was 0-25 mg/kg weight, 0. 85mg/kg weight and 8- 5mg/kg weight respectively. Normal saline was used as control. Every group contains 15 rats in 4 groups. The expression of iNOS in the heart and aorta of fetal and maternal at term was detected by immunohistochemistry technique. Results:In the nitroglycerin 0. 25 mg/kg weight group and control group,there were no expression of iNOS both in heart and aorta of fetus and maternal rats. Between the 0. 85 mg/kg weight group and 0. 25mgAg weight group, the iNOS expression was no difference among in the heart and aorta of fetus and maternal rats (P<0. 05) except in muscle cell under the endocardium of maternal rats. In the 8. 5mg/kg weight group, iNOS expressed in myocardium and vascular smooth muscle of maternal was more than those of 0. 85mg/kg weight group ( P<0. 05), while it is no difference in the heart and aorta of fetus. Conclusion: It was safety to pregnant rat treated with normal concentration of nitroglycerin. iNOS induced by super dose nitroglycerin may be cytotoxic and damag to cell and tissue.