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黄芩苷对酒精性脂肪肝条件下 Toll 样受体 4 介导的缺血/再灌注炎症反应的影响。

Effect of baicalin on toll-like receptor 4-mediated ischemia/reperfusion inflammatory responses in alcoholic fatty liver condition.

机构信息

School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.

出版信息

Toxicol Appl Pharmacol. 2012 Jan 1;258(1):43-50. doi: 10.1016/j.taap.2011.10.005. Epub 2011 Oct 14.

Abstract

Alcoholic fatty liver is susceptible to secondary stresses such as ischemia/reperfusion (I/R). Baicalin is an active component extracted from Scutellaria baicalensis, which is widely used in herbal preparations for treatment of hepatic diseases and inflammatory disorders. This study evaluated the potential beneficial effect of baicalin on I/R injury in alcoholic fatty liver. Rats were fed an alcohol liquid diet or a control isocaloric diet for 5 weeks, and then subjected to 60 min of hepatic ischemia and 5h of reperfusion. Baicalin (200mg/kg) was intraperitoneally administered 24 and 1h before ischemia. After reperfusion, baicalin attenuated the increases in serum alanine aminotransferase activity, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels in alcoholic fatty liver. The increased levels of TNF-α and IL-6 mRNA expression and inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expressions increased after reperfusion, which were higher in ethanol-fed animals, were attenuated by baicalin. In ethanol-fed animals, baicalin attenuated the increases in toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 protein expressions and the nuclear translocation of NF-κB after reperfusion. In conclusion, our findings suggest that baicalin ameliorates I/R-induced hepatocellular damage by suppressing TLR4-mediated inflammatory responses in alcoholic fatty liver.

摘要

酒精性脂肪肝容易受到缺血/再灌注(I/R)等继发性应激的影响。黄芩苷是从黄芩中提取的一种活性成分,广泛用于治疗肝脏疾病和炎症性疾病的草药制剂。本研究评估了黄芩苷对酒精性脂肪肝 I/R 损伤的潜在有益作用。大鼠给予酒精液饲或等热量对照饮食 5 周,然后进行 60 分钟肝缺血和 5 小时再灌注。黄芩苷(200mg/kg)在缺血前 24 小时和 1 小时腹腔内给药。再灌注后,黄芩苷可降低酒精性脂肪肝血清丙氨酸氨基转移酶活性、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平的升高。再灌注后 TNF-α和 IL-6mRNA 表达以及诱导型一氧化氮合酶和环氧化酶-2 蛋白和 mRNA 表达的增加,在乙醇喂养的动物中更高,被黄芩苷减弱。在乙醇喂养的动物中,黄芩苷可减弱再灌注后 toll 样受体 4(TLR4)和髓样分化因子 88 蛋白表达以及 NF-κB 的核易位。综上所述,我们的研究结果表明,黄芩苷通过抑制 TLR4 介导的炎症反应改善酒精性脂肪肝的 I/R 诱导的肝细胞损伤。

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