State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.
Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, China.
Chemosphere. 2020 Mar;243:125373. doi: 10.1016/j.chemosphere.2019.125373. Epub 2019 Nov 18.
The pyrethroid insecticide deltamethrin has been reported to have an effect on vertebrate development and cardiovascular disease. Sodium tanshinone IIA sulfonate (STS) is considered to have cardioprotective effects and melatonin is known to regulate sleep-waking cycles. In this experiment, we used transgenic zebrafish Tg (kdrl:mCherry) and Tg (myl7:GFP) to investigate whether STS and melatonin could reverse the cardiovascular toxicity and neurotoxicity induced by deltamethrin. Zebrafish embryos were exposed to 25 μg/L deltamethrin at 10 hpf and treated with 100 mmol/L STS and 1 μmol/L melatonin showed that deltamethrin treatment affected normal cardiovascular development. In situ hybridization and qRT-PCR results showed that deltamethrin could interfere with the normal expression of cardiovascular development-related genes vegfr2, shh, gata4, nkx2.5, causing functional defects in the cardiovascular system. In addition, deltamethrin could affect the sleep-waking behavior of larvae, increasing the activity of larvae, decreasing the rest behavior and the expression of hcrt, hcrtr, aanat2 were down-regulated. The addition of melatonin and STS can significantly alleviate cardiovascular toxicity and sleep-waking induced by deltamethrin, while restoring the expression of related genes to normal levels. Our study demonstrates the role of STS and melatonin in protecting cardiovascular and sleep-waking behavior caused by deltamethrin.
拟除虫菊酯杀虫剂溴氰菊酯已被报道对脊椎动物发育和心血管疾病有影响。丹参酮 IIA 磺酸钠（STS）被认为具有心脏保护作用，而褪黑素已知可调节睡眠-觉醒周期。在本实验中，我们使用转基因斑马鱼 Tg (kdrl:mCherry) 和 Tg (myl7:GFP) 来研究 STS 和褪黑素是否可以逆转溴氰菊酯引起的心血管毒性和神经毒性。斑马鱼胚胎在 10 hpf 时暴露于 25μg/L 溴氰菊酯中，并使用 100mmol/L STS 和 1μmol/L 褪黑素处理，结果表明溴氰菊酯处理会影响正常的心血管发育。原位杂交和 qRT-PCR 结果表明，溴氰菊酯可以干扰心血管发育相关基因 vegfr2、shh、gata4、nkx2.5 的正常表达，导致心血管系统功能缺陷。此外，溴氰菊酯还会影响幼虫的睡眠-觉醒行为，增加幼虫的活动，减少休息行为，下调 hcrt、hcrtr、aanat2 的表达。褪黑素和 STS 的添加可以显著缓解溴氰菊酯引起的心血管毒性和睡眠-觉醒紊乱，同时将相关基因的表达恢复到正常水平。我们的研究表明 STS 和褪黑素在保护由溴氰菊酯引起的心血管和睡眠-觉醒行为方面发挥作用。
