Tain You-Lin, Chen Chih-Cheng, Sheen Jiunn-Ming, Yu Hong-Ren, Tiao Mao-Meng, Kuo Ho-Chang, Huang Li-Tung
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
J Am Soc Hypertens. 2014 Apr;8(4):216-26. doi: 10.1016/j.jash.2014.01.009. Epub 2014 Feb 6.
Although antenatal corticosteroid is recommended to accelerate fetal lung maturation, prenatal dexamethasone exposure results in hypertension in the adult offspring. Since melatonin is a potent antioxidant and has been known to regulate blood pressure, we examined the beneficial effects of melatonin therapy in preventing prenatal dexamethasone-induced programmed hypertension. Male offspring of Sprague-Dawley rats were assigned to four groups (n = 12/group): control, dexamethasone (DEX), control + melatonin, and DEX + melatonin. Pregnant rats received intraperitoneal dexamethasone (0.1 mg/kg) from gestational day 16 to 22. In the melatonin-treatment groups, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Blood pressure was measured by an indirect tail-cuff method. Gene expression and protein levels were analyzed by real-time quantitative polymerase chain reaction and Western blotting, respectively. At 16 weeks of age, the DEX group developed hypertension, which was partly reversed by maternal melatonin therapy. Reduced nephron numbers due to prenatal dexamethasone exposure were prevented by melatonin therapy. Renal superoxide and NO levels were similar in all groups. Prenatal dexamethasone exposure led to increased mRNA expression of renin and prorenin receptor and up-regulated histone deacetylase (HDAC)-1 expression in the kidneys of 4-month-old offspring. Maternal melatonin therapy augmented renal Mas protein levels in DEX + melatonin group, and increased renal mRNA expression of HDAC-1, HDAC-2, and HDAC-8 in control and DEX offspring. Melatonin attenuated prenatal DEX-induced hypertension by restoring nephron numbers, altering RAS components, and modulating HDACs.
尽管推荐使用产前皮质类固醇来加速胎儿肺成熟，但产前暴露于地塞米松会导致成年子代出现高血压。由于褪黑素是一种强效抗氧化剂且已知可调节血压，我们研究了褪黑素疗法在预防产前地塞米松诱导的程序性高血压方面的有益作用。将Sprague-Dawley大鼠的雄性子代分为四组（每组n = 12）：对照组、地塞米松（DEX）组、对照组 + 褪黑素组和DEX + 褪黑素组。怀孕大鼠在妊娠第16天至22天接受腹腔注射地塞米松（0.1 mg/kg）。在褪黑素治疗组中，大鼠在整个怀孕和哺乳期间饮用含0.01%褪黑素的水。通过间接尾袖法测量血压。分别通过实时定量聚合酶链反应和蛋白质印迹分析基因表达和蛋白质水平。在16周龄时，DEX组出现高血压，而母体褪黑素疗法可部分逆转这一情况。褪黑素疗法可预防因产前暴露于地塞米松而导致的肾单位数量减少。所有组的肾脏超氧化物和一氧化氮水平相似。产前暴露于地塞米松导致4月龄子代肾脏中肾素和肾素原受体的mRNA表达增加以及组蛋白脱乙酰酶（HDAC）-1表达上调。母体褪黑素疗法增加了DEX + 褪黑素组的肾脏Mas蛋白水平，并增加了对照组和DEX子代肾脏中HDAC-1、HDAC-2和HDAC-8的mRNA表达。褪黑素通过恢复肾单位数量、改变肾素-血管紧张素系统（RAS）成分和调节HDAC来减轻产前DEX诱导的高血压。
