This study is the first to examine the possible mechanism by which long-term exposure to permethrin (PER) can promote arterial retention of proatherogenic lipid and lipoproteins and related vascular dysfunction in rats. Experimental animals were administered two doses of oral PER, PER-1 (2.5 mg/kg/bw) and PER-2 (5 mg/kg/bw), for 90 consecutive days. The results indicated that both PER-1 and PER-2 increased plasmatic and aortic total cholesterol, low-density lipoprotein cholesterol (LDL-C), apo B-100, and oxidized LDL together with arterial scavenger LDL receptors (CD36) but markedly reduced plasmatic and hepatic high-density lipoprotein cholesterol and native LDL receptors in aortic and hepatic tissue. The levels of malondialdehyde, protein carbonyl, and reactive oxygen species were significantly higher, and glutathione content as well as catalase, superoxide dismutase, and glutathione peroxidase activities were suppressed in the aorta of the PER-1 and PER-2 groups. The arterial oxidative damage possibly caused by PER was clearly demonstrated by hematoxylin and eosin histological analysis. Moreover, PER treatment aggravated the inflammatory responses through enhancement of the production of proinflammatory cytokines (tumor necrosis factor–α, interleukin-2, and interleukin-6) in both plasma and aorta. Furthermore, PER-1 and PER-2 potentiated the dysregulation of the aortic extracellular matrix (ECM) content by increasing mRNA activation of collagens I and III. The abundant histological collagen deposition observed in the media and adventitia of intoxicated rats using Masson's trichrome staining corroborates the observed change in ECM. These data showed that oxidative stress related to PER exposure increases the arterial accumulation of lipoprotein biomarkers, likely by actions on both LDL and CD36 receptors, together with the disruption of the aortic ECM.

这项研究首次探讨了长期暴露于氯菊酯（PER）可以促进大鼠动脉粥样硬化前体脂和脂蛋白的动脉滞留以及相关血管功能障碍的可能机制。给实验动物连续90天服用两种剂量的口服PER，PER-1（2.5 mg / kg / bw）和PER-2（5 mg / kg / bw）。结果表明，PER-1和PER-2均可增加血浆和主动脉总胆固醇，低密度脂蛋白胆固醇（LDL-C），载脂蛋白B-100和氧化型LDL以及动脉清除剂LDL受体（CD36），但显着降低主动脉和肝脏组织中的血浆和肝脏高密度脂蛋白胆固醇以及天然LDL受体。丙二醛，蛋白质羰基和活性氧的含量明显更高，谷胱甘肽含量和过氧化氢酶，PER-1和PER-2组的主动脉中的超氧化物歧化酶和谷胱甘肽过氧化物酶活性受到抑制。苏木精和曙红的组织学分析清楚地证明了PER可能引起的动脉氧化损伤。此外，PER治疗通过增强血浆和主动脉中促炎细胞因子（肿瘤坏死因子-α，白介素2和白介素6）的产生而加剧了炎症反应。此外，PER-1和PER-2通过增加胶原蛋白I和III的mRNA激活来增强主动脉细胞外基质（ECM）含量的失调。使用Masson三色染色在中毒大鼠的中膜和外膜中观察到大量组织胶原沉积，证实了所观察到的ECM变化。