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二氢槲皮素对肝性脑病大鼠的肝保护和神经保护作用。

Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats.

机构信息

Medical Pharmacology Department, Faculty of Medicine, Ataturk University, 25100, Erzurum, Turkey.

Pharmacology Department, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.

出版信息

Metab Brain Dis. 2022 Jun;37(5):1541-1556. doi: 10.1007/s11011-022-00952-3. Epub 2022 Mar 17.

Abstract

This study was planned to assess the potential protective effects of taxifolin against thioacetamide-induced hepatic encephalopathy and subsequently to portray its behavioural results. The experimental model was induced with three doses of (200 mg/kg i.p.) thioacetamide and taxifolin (50 and 100 mg/kg, p.o.) was administered for fourteen days. Taxifolin effectively attenuated hepatic encephalopathy through decrease in AST, ALT, ALP and LDH concentrations and improvement of hyperammonemia, and increase in antioxidant capacity by decreasing MDA, ROS, and increasing CAT and GSH. In addition, the expressions of NF-κB, TNF-α, IL-1β, caspase-3 and Bax was down-regulated while IL-10 and Bcl-2 expressions were up-regulated with taxifolin treatment. The recovery was confirmed by downregulation of iNOS and 8-OHdG expressions in our immunohistochemical analysis. Taxifolin treatment reduced the disrupting role of thioacetamide as seen by corrected hyperammonemia as well as preservation of astrocyte and hepatocyte structure. Elevated plus maze and locomotor activity tests also proved that taxifolin might repeal the neurobehavioral disabilities. In conclusion, taxifolin has shown hepatoprotective and neuroprotective roles with antioxidant and anti-inflammatory effects, as well as suppressing the excessive release of ammonia, and it eventually reversed neurobehavioral impairments.

摘要

本研究旨在评估圣草酚对硫代乙酰胺诱导的肝性脑病的潜在保护作用,并随后描述其行为学结果。实验模型采用三种剂量(200mg/kg 腹腔注射)的硫代乙酰胺诱导,圣草酚(50 和 100mg/kg,口服)给药 14 天。圣草酚通过降低 AST、ALT、ALP 和 LDH 浓度以及改善高氨血症,同时通过降低 MDA、ROS、增加 CAT 和 GSH 来提高抗氧化能力,有效地减轻了肝性脑病。此外,圣草酚处理还下调了 NF-κB、TNF-α、IL-1β、caspase-3 和 Bax 的表达,同时上调了 IL-10 和 Bcl-2 的表达。我们的免疫组织化学分析表明,圣草酚治疗降低了 iNOS 和 8-OHdG 的表达,从而证实了这种恢复作用。圣草酚治疗通过纠正高氨血症以及保存星形胶质细胞和肝细胞结构,减少了硫代乙酰胺的破坏作用。高架十字迷宫和运动活性测试也证明了圣草酚可能会逆转神经行为障碍。总之,圣草酚具有抗氧化和抗炎作用,能保护肝脏和神经,抑制氨的过度释放,最终逆转神经行为损伤。

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