氯高铁血红素对妊娠期高血压大鼠的治疗及机制  

Therapeutic effect of hemin on gestational hypertension in rats and the mechanism

作　　者：龙买连 夏爱斌[1] 程春霞[1] 李瑞珍[1] 

机构地区：[1]中南大学湘雅三医院妇产科,湖南长沙410013

出　　处：《南方医科大学学报》2015年第4期583-586,共4页Journal of Southern Medical University

基　　金：湖南省自然科学基金(2015JJ4050)

摘　　要：目的初步探讨血红素氧合酶诱导剂氯高铁血红素(Hemin)对妊娠期高血压(HDCP)大鼠的治疗作用及可能调控机制。方法将18只受孕SD大鼠于妊娠第12天随机分为3组(6只/组):HDCP模型组、Hemin干预组、正常妊娠组。HDCP模型组和Hemin干预组于妊娠第14天起连续7 d予亚硝基左旋精氨酸甲酯(80 mg/kg)灌胃建立HDCP模型,正常妊娠组予等量生理盐水灌胃处理,Hemin干预组于妊娠第16天起每日下午腹腔注射Hemin(30 mg/kg)。用分光光度法测定各组胎盘组织血红素氧合酶(HO)的活性和碳氧血红蛋白(COHb)水平,ELSIA测定各组胎盘组织匀浆上清液可溶性血管内皮生长因子受体-1(s FIt-1)、血管内皮生长因子(VEGF)水平。结果妊娠第20天,HDCP模型组孕鼠血压和24 h尿蛋白明显高于正常妊娠组和Hemin干预组(P<0.05),而HO活性和COHb含量明显低于正常妊娠组和Hemin干预组(P<0.05),Hemin干预组血压及24 h尿蛋白高于正常组(P<0.05),而HO活性和COHb含量较正常组低(P<0.05);HDCP模型组孕鼠胎盘组织s FIt-1水平明显高于正常妊娠组和Hemin干预组(P<0.05),而胎盘组织中VEGF水平明显低于正常妊娠组和Hemin干预组(P<0.05),Hemin干预组孕鼠胎盘组织s FIt-1水平高于正常组水平(P<0.05),而VEGF水平低于正常组水平(P<0.05)。结论 Hemin能够降低妊娠期高血压孕鼠的血压及尿蛋白,其可能机制是通过上调胎盘组织中HO的活性,增加代谢产物CO,降低胎盘组织中s FIt-1,并升高VEGF水平来发挥调控作用的。Objective To investigate the therapeutic effects of hemin, an inducer of heme oxygenase, in a rat model of gestational hypertension and explore the possible mechanism. Methods Eighteen pregnant SD rats at day 12 of gestation were randomized equally into gestational hypertension model group, hemin treatment group, and normal pregnancy （control） group. In the former two groups, the rats were subjected to daily nitro-L-arginine methyl ester （L-NAME, 80 mg/kg） gavage since gestational day 14 for 7 consecutive days to induce gestational hypertension; saline was administered in the same manner in the control rats. The rats in hemin group received daily intraperitoneal injection of hemin （30 mg/kg） starting from gestational day 16. HO activity and carboxyhemoglobin （COHb） level in rat placental tissue were detected with spectrophotometric method, and soluble vascular endothelial growth factor receptor-1 （sFIt-1） and vascular endothelial growth factor （VEGF） level in the placental tissue homogenate supernatant were detected using ELSIA. Results At gestational day 20, the blood pressure and 24-h urinary protein were significantly higher in the model group than in the other two groups （P〈0.05）, and were higher in hemin group than in the control group （P〈0.05）;HO activity and COHb content in the placenta tissue were the lowest in the model group （P〈0.05）, and was lower in hemin group than in the control group （P〈0.05）. The level of sFIt-1 was significantly higher and VEGF level significantly lower in the model group than in the other two groups （P〈0.05）;sFIt-1 level remained higher and VEGF lower in hemin group than in the control group （P〈0.05）. Conclusion Hemin can reduce blood pressure and urinary protein in rats with gestational hypertension possibly by up-regulating HO activity, enhancing carbon monoxide production, reducing sFIt-1 and increasing VEGF in the placental tissue.

关 键 词：氯高铁血红素 血红素氧合酶 妊娠期高血压 可溶性血管内皮生长因子受体-1 血管内皮生长因子 

分 类 号：R714.246[医药卫生—妇产科学]