School of Public Health and Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
School of Public Health and Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
Chemosphere. 2021 Mar;267:128867. doi: 10.1016/j.chemosphere.2020.128867. Epub 2020 Nov 5.
Decabromodiphenyl ethane (DBDPE) is a novel environmental pollutant that has attracted growing attention. Previous studies have indicated that DBDPE could induce vascular endothelial injury and cardiovascular damage, but the underlying mechanisms are not well understood. This study was designed to examine the mechanisms of DBDPE induces vascular endothelial injury. In vivo, Sprague-Dawley rats were administered with 0, 5, 50, 500 mg/kg bw/day of DBDPE via gavage for 28 days. Results showed that DBDPE could damage abdominal aortas morphological and ultrastructural structure and increase the protein levels of interleukin 1β (IL-1β) and interleukin 18 (IL-18) of the abdominal aortas. Moreover, DBDPE induced NLRP3 inflammasome activation and activated caspase-1 in abdominal aorta endothelium of rats. In vitro, human vascular endothelial cells (HAECs) were treated with different concentrations of DBDPE (0, 6.25, 12.5, 25, 50, and 100 μM). DBDPE not only induced cytotoxicity and reactive oxygen species (ROS) generation in HAECs but also caused HAECs pyroptosis, which was evidenced by the elevated expression of Nod-like receptor protein -3 (NLRP3), ASC, and caspase-1 in DBDPE-treated group. To further elucidate the effects of NLRP3 inflammasome on DBDPE-induced HAECs pyroptosis, we constructed NLRP3 knockdown HAECs by lentivirus-mediated short hairpin RNA (shRNA). And the results showed that NLRP3 knockdown downregulated DBDPE-induced increases of caspase-1 activity and caspase-1, ASC and NLRP3 mRNA and protein expression levels. Accordingly, our data suggested that DBDPE may damage vascular endothelium by NLRP3 inflammasome-mediated endothelial cells pyroptosis.
十溴二苯乙烷（DBDPE）是一种新型环境污染物，引起了越来越多的关注。先前的研究表明，DBDPE 可诱导血管内皮损伤和心血管损伤，但具体机制尚不清楚。本研究旨在探讨 DBDPE 诱导血管内皮损伤的机制。体内实验中，将 Sprague-Dawley 大鼠通过灌胃给予 0、5、50、500mg/kg·bw/day 的 DBDPE，连续 28 天。结果表明，DBDPE 可损伤大鼠的腹主动脉形态和超微结构，并增加腹主动脉中白细胞介素 1β（IL-1β）和白细胞介素 18（IL-18）的蛋白水平。此外，DBDPE 诱导了大鼠腹主动脉内皮中 NLRP3 炎性小体的激活和半胱天冬酶-1 的激活。体外实验中，用不同浓度的 DBDPE（0、6.25、12.5、25、50 和 100μM）处理人血管内皮细胞（HAECs）。结果显示，DBDPE 不仅诱导了 HAECs 的细胞毒性和活性氧（ROS）生成，还导致了 HAECs 的细胞焦亡，表现为 DBDPE 处理组中 Nod 样受体蛋白 3（NLRP3）、ASC 和半胱天冬酶-1 的表达升高。为了进一步阐明 NLRP3 炎性小体对 DBDPE 诱导的 HAECs 细胞焦亡的影响，我们通过慢病毒介导的短发夹 RNA（shRNA）构建了 NLRP3 敲低的 HAECs。结果表明，NLRP3 敲低下调了 DBDPE 诱导的半胱天冬酶-1 活性以及半胱天冬酶-1、ASC 和 NLRP3 mRNA 和蛋白表达水平的增加。综上，我们的数据表明，DBDPE 可能通过 NLRP3 炎性小体介导的内皮细胞细胞焦亡来损伤血管内皮。
