CAJ | 학술논문

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（sFIt-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sFIt-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sFIt-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sFIt-1，并升高VEGF水平来发挥调控作用的。
목적：초보탐토혈홍소양합매유도제록고철혈홍소（Hemin）대임신기고혈압（HDCP）대서적치료작용급가능조공궤제。방법장18지수잉SD대서우임신제12천수궤분위3조（6지/조）：HDCP모형조、Hemin간예조、정상임신조。HDCP모형조화Hemin간예조우임신제14천기련속7 d여아초기좌선정안산갑지（80 mg/kg）관위건립HDCP모형，정상임신조여등량생리염수관위처리，Hemin간예조우임신제16천기매일하오복강주사Hemin（30 mg/kg）。용분광광도법측정각조태반조직혈홍소양합매（HO）적활성화탄양혈홍단백（COHb）수평，ELSIA측정각조태반조직균장상청액가용성혈관내피생장인자수체-1（sFIt-1）、혈관내피생장인자（VEGF）수평。결과임신제20천，HDCP모형조잉서혈압화24 h뇨단백명현고우정상임신조화Hemin간예조（P<0.05），이HO활성화COHb함량명현저우정상임신조화Hemin간예조（P<0.05），Hemin간예조혈압급24 h뇨단백고우정상조（P<0.05），이HO활성화COHb함량교정상조저（P<0.05）；HDCP모형조잉서태반조직sFIt-1수평명현고우정상임신조화Hemin간예조（P<0.05），이태반조직중VEGF수평명현저우정상임신조화Hemin간예조（P<0.05），Hemin간예조잉서태반조직sFIt-1수평고우정상조수평（P<0.05），이VEGF수평저우정상조수평（P<0.05）。결론 Hemin능구강저임신기고혈압잉서적혈압급뇨단백，기가능궤제시통과상조태반조직중HO적활성，증가대사산물CO，강저태반조직중sFIt-1，병승고VEGF수평래발휘조공작용적。
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.