Hsu Chien-Ning, Hung Chih-Hsing, Hou Chih-Yao, Chang Chi-I, Tain You-Lin
Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
Antioxidants (Basel). 2021 Aug 30;10(9):1393. doi: 10.3390/antiox10091393.
Exposure to environmental chemicals during pregnancy and lactation is a contributing factor in gut microbiota dysbiosis and linked to programming of hypertension. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin, induces toxic effects by mediating aryl hydrocarbon receptor (AHR). Resveratrol, a potent antioxidant with prebiotic properties, can possess high affinity for AHR and protect against TCDD-activated AHR attack. We examined whether perinatal resveratrol therapy prevents offspring hypertension programmed by maternal TCDD exposure and whether its beneficial effects are related to reshaping gut microbiota and antagonizing AHR-mediated T helper 17 (TH17) cells responses using a maternal TCDD exposure rat model. Pregnant Sprague-Dawley rats were given a weekly oral dose of TCDD 200 ng/kg for four doses (T), 50 mg/L of resveratrol in drinking water (CR), TCDD + resveratrol (TR), or vehicle (C) in pregnancy and lactation periods. Male offspring ( = 7-8/group) were sacrificed at the age of 12 weeks. Perinatal TCDD exposure caused elevated blood pressure in adult male offspring, which resveratrol supplementation prevented. Additionally, the TCDD-induced programming of hypertension is coincided with the activation of AHR signaling, TH17-induced renal inflammation, and alterations of gut microbiota compositions. Conversely, TCDD-mediated induction of AHR signaling and TH17 responses were restored by maternal resveratrol supplementation. Furthermore, maternal resveratrol supplementation prevented the programming of hypertension and was related to increased genera , , and . Taken together, these results suggest that the interplay between gut microbiota, AHR-mediated TH17 responses, and renal inflammation in the gut and kidneys may play an important role in the action of resveratrol against TCDD-induced programming of hypertension.
孕期和哺乳期接触环境化学物质是肠道微生物群失调的一个促成因素，并与高血压的发生有关。2,3,7,8-四氯二苯并对二恶英（TCDD）是毒性最强的二恶英，通过介导芳烃受体（AHR）诱导毒性作用。白藜芦醇是一种具有益生元特性的强效抗氧化剂，对AHR具有高亲和力，可抵御TCDD激活的AHR攻击。我们使用母体TCDD暴露大鼠模型，研究了围产期白藜芦醇治疗是否能预防母体TCDD暴露导致的子代高血压，以及其有益作用是否与重塑肠道微生物群和拮抗AHR介导的辅助性T细胞17（TH17）细胞反应有关。将怀孕的斯普拉格-道利大鼠在孕期和哺乳期每周口服一次剂量为200 ng/kg的TCDD，共四次（T组），饮用水中添加50 mg/L白藜芦醇（CR组），TCDD+白藜芦醇（TR组），或给予溶剂（C组）。12周龄时处死雄性子代（每组n = 7-8只）。围产期TCDD暴露导致成年雄性子代血压升高，补充白藜芦醇可预防。此外，TCDD诱导的高血压发生与AHR信号激活、TH17诱导的肾脏炎症以及肠道微生物群组成的改变同时出现。相反，母体补充白藜芦醇可恢复TCDD介导的AHR信号和TH17反应的诱导。此外，母体补充白藜芦醇可预防高血压的发生，这与属、属和属的增加有关。综上所述，这些结果表明，肠道微生物群、AHR介导的TH17反应以及肠道和肾脏中的肾脏炎症之间的相互作用可能在白藜芦醇对抗TCDD诱导的高血压发生作用中起重要作用。
