Zhou Dan, Ai Qing, Lin Ling, Gong Xianqiong, Ge Pu, Che Qian, Wan Jingyuan, Wen Aiqing, Zhang Li
Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Department of Physiology, Chongqing Medical University, Chongqing, China.
Innate Immun. 2015 Oct;21(7):698-705. doi: 10.1177/1753425915586231. Epub 2015 May 15.
The AMP-activated protein kinase (AMPK)-mediated energy-sensing signals play important roles in reprogramming the expression of inflammatory genes. In the present study, the potential effects of the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) were investigated in a mouse model with LPS/D-Gal-induced acute hepatitis. Our experimental data indicated that treatment with AICAR suppressed the elevation of plasma aminotransferases and alleviated the histopathological abnormalities in mice exposed to LPS/D-Gal. Treatment with AICAR also inhibited the LPS/D-Gal-induced up-regulation of TNF-α, NO and myeloperoxidase. In addition, the LPS/D-Gal-induced expression of pro-apoptotic factor Bax, cleavage of caspase-3, elevation of hepatic caspase-3, caspase-8, caspase-9 activities and induction of terminal deoxynucleotidyl transferase-mediated nucleotide nick-end labeling-positive cells were all suppressed by AICAR. These results suggested that the AMPK activator AICAR could attenuate LPS/D-Gal-induced acute hepatitis, which implies that AMPK might become a novel target for the treatment of inflammation-based liver disorders.
AMP激活的蛋白激酶（AMPK）介导的能量感应信号在炎症基因表达重编程中发挥重要作用。在本研究中，在脂多糖/ D-半乳糖诱导的急性肝炎小鼠模型中研究了AMPK激活剂5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR）的潜在作用。我们的实验数据表明，用AICAR处理可抑制血浆转氨酶升高，并减轻暴露于脂多糖/ D-半乳糖的小鼠的组织病理学异常。用AICAR处理还可抑制脂多糖/ D-半乳糖诱导的TNF-α、NO和髓过氧化物酶上调。此外，脂多糖/ D-半乳糖诱导的促凋亡因子Bax表达、caspase-3裂解、肝caspase-3、caspase-8、caspase-9活性升高以及末端脱氧核苷酸转移酶介导的核苷酸缺口末端标记阳性细胞的诱导均被AICAR抑制。这些结果表明，AMPK激活剂AICAR可减轻脂多糖/ D-半乳糖诱导的急性肝炎，这意味着AMPK可能成为治疗基于炎症的肝脏疾病的新靶点。
