Long Mai-Lian, Xia Ai-Bin, Cheng Chun-Xia, Li Rui-Zhen
Department of Gynecology and Obstetrics, Third Xiangya Hospital of Central South University, Changsha 410013, China. E-mail:
Nan Fang Yi Ke Da Xue Xue Bao. 2015 Apr;35(4):583-6.
To investigate the therapeutic effects of hemin, an inducer of heme oxygenase, in a rat model of gestational hypertension and explore the possible mechanism.
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 (sFlt-1) and vascular endothelial growth factor (VEGF) level in the placental tissue homogenate supernatant were detected using ELSIA.
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 sFlt-1 was significantly higher and VEGF level significantly lower in the model group than in the other two groups (P<0.05); sFlt-1 level remained higher and VEGF lower in hemin group than in the control group (P<0.05).
Hemin can reduce blood pressure and urinary protein in rats with gestational hypertension possibly by up-regulating HO activity, enhancing carbon monoxide production, reducing sFlt-1 and increasing VEGF in the placental tissue.
研究血红素加氧酶诱导剂血红素对妊娠高血压大鼠模型的治疗作用，并探讨其可能机制。
18只妊娠第12天的SD孕鼠被随机等分为妊娠高血压模型组、血红素治疗组和正常妊娠（对照）组。在前两组中，自妊娠第14天起，大鼠每天接受硝基-L-精氨酸甲酯（L-NAME，80mg/kg）灌胃，连续7天以诱导妊娠高血压；对照组大鼠以相同方式给予生理盐水。血红素组大鼠自妊娠第16天起每天腹腔注射血红素（30mg/kg）。采用分光光度法检测大鼠胎盘组织中的血红素加氧酶（HO）活性和碳氧血红蛋白（COHb）水平，采用酶联免疫吸附测定法（ELISA）检测胎盘组织匀浆上清液中的可溶性血管内皮生长因子受体-1（sFlt-1）和血管内皮生长因子（VEGF）水平。
在妊娠第20天，模型组的血压和24小时尿蛋白显著高于其他两组（P<0.05），血红素组高于对照组（P<0.05）；胎盘组织中的HO活性和COHb含量在模型组中最低（P<0.05），血红素组低于对照组（P<0.05）。模型组中的sFlt-1水平显著高于其他两组，VEGF水平显著低于其他两组（P<0.05）；血红素组中的sFlt-1水平仍高于对照组，VEGF水平低于对照组（P<0.05）。
血红素可能通过上调HO活性、增加一氧化碳生成、降低胎盘组织中的sFlt-1并增加VEGF，从而降低妊娠高血压大鼠的血压和尿蛋白。
