Cao Jie, Zhao Xin, Liu Ming-Jiang, Zheng Hui, Li Jin-Gui
School of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
Zhongguo Zhong Yao Za Zhi. 2018 May;43(10):2123-2128. doi: 10.19540/j.cnki.cjcmm.20180125.009.
Autoimmune liver disease is a refractory disease clinically, and there is no particularly effective drug at present. Therefore, it is of important clinical value to develop new effective intervention drugs for the prevention and treatment of autoimmune liver disease. In order to investigate the potential protective effect of artesunate (Art) on concanavalin A (Con A)-induced autoimmune liver injury, different doses of Art (27, 54, 108 mg·kg⁻¹) were orally administered to mice for consecutive 7 days, respectively. Then the Con A was injected into mice via tail vein to induce liver injury models. 8 h after modeling, the mice were sacrificed. The serum and liver tissue were collected for detecting the level of alanine aminotransferase (ALT), and aspartate transaminase (AST), liver pathological histopathology, inflammatory cytokines and nuclear factor (NF-κB) key protein expression level. The results showed that 108 mg·kg⁻¹ Art remarkably reduced Con A-induced liver indexes and serum transaminase levels (ALT and AST) as compared with model group(<0.01). Meanwhile, the liver histopathological changes were obviously alleviated with a significant decrease of pro-inflammatory cytokine including tumor necrosis factor (TNF-α), interferon (IFN-γ), interleukin (IL-6), IL-17 and a higher increase of anti-inflammatory cytokine IL-10 (<0.01). Western blot results showed that 108 mg·kg⁻¹ Art markedly inhibited the expressions of p-p65 and p-IκBα proteins (<0.01). The specific inhibitor of NF-κB, pyrrolidinedithiocarbamate (PDTC) could also significantly inhibit the expressions of p-p65 and p-IκBα with and alleviate liver injuries. Therefore, our results indicated that Art may have a protective action against Con A-induced autoimmune liver injury mainly by suppressing NF-κB signal pathway in mice. The study provides scientific reference for artesunate usage in preventing autoimmune liver injury.
自身免疫性肝病是临床上的难治性疾病，目前尚无特效药物。因此，开发新的有效干预药物用于防治自身免疫性肝病具有重要的临床价值。为探讨青蒿琥酯（Art）对刀豆蛋白A（Con A）诱导的自身免疫性肝损伤的潜在保护作用，将不同剂量的Art（27、54、108 mg·kg⁻¹）分别连续7天灌胃给予小鼠。然后经尾静脉注射Con A诱导肝损伤模型。造模8小时后处死小鼠，收集血清和肝组织，检测丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平、肝脏病理组织学、炎性细胞因子及核因子（NF-κB）关键蛋白表达水平。结果显示，与模型组相比，108 mg·kg⁻¹ Art显著降低了Con A诱导的肝脏指数和血清转氨酶水平（ALT和AST）（<0.01）。同时，肝脏组织病理学变化明显减轻，促炎细胞因子包括肿瘤坏死因子（TNF-α）、干扰素（IFN-γ）、白细胞介素（IL-6）、IL-17显著降低，抗炎细胞因子IL-10显著升高（<0.01）。蛋白质免疫印迹结果显示，108 mg·kg⁻¹ Art显著抑制p-p65和p-IκBα蛋白的表达（<0.01）。NF-κB特异性抑制剂吡咯烷二硫代氨基甲酸盐（PDTC）也能显著抑制p-p65和p-IκBα的表达并减轻肝损伤。因此，我们的结果表明，Art可能主要通过抑制小鼠NF-κB信号通路对Con A诱导的自身免疫性肝损伤具有保护作用。该研究为青蒿琥酯预防自身免疫性肝损伤的应用提供了科学参考。
