Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Int J Mol Sci. 2018 Aug 20;19(8):2459. doi: 10.3390/ijms19082459.
Hypertension can originate from early-life adverse environmental in utero exposure to dexamethasone (DEX) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Since DEX and TCDD are related to the aryl hydrocarbon receptor (AHR) signaling pathway, we examined whether resveratrol, an AHR modulator and antioxidant, could prevent programmed hypertension via regulating AHR signaling and oxidative stress. Groups of four-month-old male rat offspring were studied ( = 7⁻8 per group): control, DEX (0.1 mg/kg i.p. from a gestational age of 16 to 22 days), TCDD (200 ng/kg in four once-weekly oral doses), DEX + TCDD, and DEX + TCDD + R (resveratrol 0.05% in drinking water throughout pregnancy and lactation). Maternal TCDD exposure aggravated prenatal DEX-induced hypertension in adult male offspring, which maternal resveratrol therapy prevented. Maternal TCDD exposure aggravated DEX-induced oxidative damage in offspring kidneys, which was prevented by resveratrol therapy. Maternal resveratrol therapy decreased asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels, thereby preventing combined DEX and TCDD exposure-induced programmed hypertension. Increases in renal and expression induced by DEX + TCDD exposure were restored by resveratrol therapy. The beneficial effects of resveratrol on DEX + TCDD-induced hypertension relate to reduced renal mRNA expression of , , and expression. Thus, the beneficial effects of resveratrol on DEX + TCDD-induced hypertension include reduction of oxidative stress, restoration of nitric oxide (NO) bioavailability, blockade of the renin⁻angiotensin system (RAS), and antagonizing AHR signaling pathway.
高血压可能源于生命早期子宫内暴露于地塞米松（DEX）或 2,3,7,8-四氯二苯并对二恶英（TCDD）等不良环境因素。由于 DEX 和 TCDD 与芳烃受体（AHR）信号通路有关，我们研究了白藜芦醇（一种 AHR 调节剂和抗氧化剂）是否可以通过调节 AHR 信号和氧化应激来预防程序化高血压。研究了四个月大的雄性大鼠后代（每组 7-8 只）：对照组、DEX（从妊娠第 16 天到第 22 天腹腔注射 0.1mg/kg）、TCDD（4 次每周口服一次 200ng/kg）、DEX+TCDD 和 DEX+TCDD+R（妊娠和哺乳期饮用水中白藜芦醇 0.05%）。母体 TCDD 暴露加重了产前 DEX 诱导的成年雄性后代高血压，而母体白藜芦醇治疗则预防了这种情况。母体 TCDD 暴露加重了 DEX 诱导的后代肾脏氧化损伤，而白藜芦醇治疗则预防了这种损伤。母体白藜芦醇治疗降低了不对称和对称二甲基精氨酸（ADMA 和 SDMA）水平，从而预防了 DEX 和 TCDD 联合暴露引起的程序化高血压。DEX+TCDD 暴露引起的肾 和 表达增加被白藜芦醇治疗恢复。白藜芦醇对 DEX+TCDD 诱导的高血压的有益作用与降低肾 mRNA 表达有关， 、 和 。因此，白藜芦醇对 DEX+TCDD 诱导的高血压的有益作用包括减少氧化应激、恢复一氧化氮（NO）生物利用度、阻断肾素-血管紧张素系统（RAS）和拮抗 AHR 信号通路。
