Abstract：
The purpose of this study was to demonstrate the neuroprotective effect of Melissa officinalis extract (MEE) against brain damage associated with hypothyroidism induced by propylthiouracil (PTU) and/or γ-radiation (IR) in rats. Hypothyroidism induction and/or exposure to IR resulted in a significant decrease in the serum levels of T3 and T4 associated with increased levels of lipid peroxidation end product, malondialdehyde (MDA), and nitrites (NO) in the brain tissue homogenate. Also, hypothyroidism and /or exposure to IR markedly enhance the endoplasmic reticulum stress by upregulating the gene expressions of the protein kinase RNA-like endoplasmic reticulum kinase (PERK), activated transcription factor 6 (ATF6), endoplasmic reticulum-associated degradation (ERAD), and CCAAT/enhancer-binding protein homologous protein (CHOP) in the brain tissue homogenate associated with a proapoptotic state which indicated by the overexpression of Bax, BCl2, and caspase-12 that culminates in brain damage. Meanwhile, the PTU and /or IR-exposed rats treated with MEE reduced oxidative stress and ERAD through ATF6. Also, the MEE treatment prevented the Bax and caspase-12 gene expression from increasing. This treatment in hypothyroid animals was associated with neuronal protection as indicated by the downregulation in the gene expressions of the microtubule-associated protein tau (MAPT) and amyloid precursor protein (APP) in the brain tissue. Furthermore, the administration of MEE ameliorates the histological structure of brain tissue. In conclusion, MEE might prevent hypothyroidism-induced brain damage associated with oxidative stress and endoplasmic reticulum stress.
摘要：
这项研究的目的是证明蜂花提取物（MEE）对丙基硫氧嘧啶（PTU）和/或γ辐射（IR）引起的甲状腺功能减退相关的脑损伤的神经保护作用。甲状腺功能减退诱导和/或暴露于IR导致血清T3和T4水平显著降低，与脂质过氧化终产物水平升高相关，丙二醛（MDA），脑组织匀浆中的亚硝酸盐（NO）。此外，甲状腺功能减退和/或暴露于IR通过上调蛋白激酶RNA样内质网激酶（PERK）的基因表达显着增强内质网应激，激活的转录因子6（ATF6），内质网相关降解（ERAD），脑组织匀浆中的CCAAT/增强子结合蛋白同源蛋白（CHOP）与Bax的过表达表明的促凋亡状态有关，BCl2和caspase-12最终导致脑损伤。同时,用MEE治疗的PTU和/或IR暴露的大鼠通过ATF6降低了氧化应激和ERAD。此外，MEE治疗阻止Bax和caspase-12基因表达增加。甲状腺功能减退动物的这种治疗与神经元保护有关，如脑组织中微管相关蛋白tau（MAPT）和淀粉样前体蛋白（APP）的基因表达下调所示。此外，MEE的给药改善了脑组织的组织学结构。总之,MEE可能预防甲状腺功能减退症引起的与氧化应激和内质网应激相关的脑损伤。
