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白藜芦醇对热应激介导的老年大鼠肝损伤的适应原抗衰老潜力:HSP70 和 NF-kB 信号通路的作用。

The adaptogenic anti-ageing potential of resveratrol against heat stress-mediated liver injury in aged rats: Role of HSP70 and NF-kB signalling.

机构信息

Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Edfina, 22758, Egypt.

Department of Histology and Cytology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22516, Egypt.

出版信息

J Therm Biol. 2019 Jul;83:8-21. doi: 10.1016/j.jtherbio.2019.04.012. Epub 2019 May 1.

Abstract

Heat stress (HS) is a major international problem which has attracted a considerable attention due to its oxidative tissue effects and high morbidity and mortality rates, especially among elderly people. Discovering an effective antioxidant is pivotal for overcoming HS-induced injury. Therefore, the aim of this study was to estimate the hepatic protective effects of orally supplemented resveratrol (RES) against HS-mediated liver injury in young and old male Wistar albino rats. Compared to control rats, RES administered orally at a dose of 20 mg/kg BW for 21 successive days efficiently ameliorated HS-induced oxidative damage by significantly increasing (P ≤ 0.05) the level of reduced glutathione and glutathione peroxidase, and decreasing the levels of malondialdehyde and TNF-α in hepatic tissue of both young and aged rats. However, level of NF-κB was downregulated significantly in aged rats rather than young rats. Moreover, RES significantly decreased (P ≤ 0.05) the serum levels of aspartate transaminase and alkaline phosphatase in both ages of rats compared to their corresponding HS-stressed rats. Furthermore, RES upregulated the immunohistochemical expression of caspase 3 and heat shock protein 70 in young and aged rats, however it was more pronounced in young one. In addition, RES administration moderately normalized (P ≤ 0.0001) the harmful effects of HS on the hepatic architecture of both young and aged rats. In conclusion, this study reveals for the first time that RES exerts promising hepato-ameliorative effects against HS-induced oxidative stress in the young and aged rats via its antioxidant, anti-inflammatory, and anti-apoptotic effect, as well as via its inhibitory effect against the NF-κB signalling in a cellular system.

摘要

热应激(HS)是一个主要的国际问题,由于其对组织的氧化作用以及高发病率和死亡率,尤其是在老年人中,引起了相当大的关注。发现有效的抗氧化剂对于克服 HS 引起的损伤至关重要。因此,本研究的目的是评估口服补充白藜芦醇(RES)对年轻和老年雄性 Wistar 白化大鼠 HS 介导的肝损伤的肝保护作用。与对照组大鼠相比,连续 21 天每天口服给予 20mg/kg BW 的 RES 可通过显著增加(P≤0.05)还原型谷胱甘肽和谷胱甘肽过氧化物酶的水平,以及降低丙二醛和 TNF-α的水平,有效地改善 HS 引起的氧化损伤。年轻和老年大鼠的肝组织。然而,NF-κB 的水平在老年大鼠中显著下调,而在年轻大鼠中则没有。此外,与相应的 HS 应激大鼠相比,RES 可显著降低(P≤0.05)两种年龄大鼠的血清天冬氨酸转氨酶和碱性磷酸酶水平。此外,RES 上调了年轻和老年大鼠中 caspase 3 和热休克蛋白 70 的免疫组织化学表达,然而在年轻大鼠中更为明显。此外,RES 适度地使 HS 对年轻和老年大鼠肝组织的有害作用正常化(P≤0.0001)。总之,本研究首次表明,RES 通过其抗氧化、抗炎和抗细胞凋亡作用,以及通过其对 NF-κB 信号通路的抑制作用,在细胞系统中对年轻和老年大鼠的 HS 诱导的氧化应激发挥了有希望的肝保护作用。

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