Department of Geriatric Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012, PR China.
Department of Geriatric Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012, PR China.
Chem Biol Interact. 2018 Jun 1;289:47-56. doi: 10.1016/j.cbi.2018.04.025. Epub 2018 Apr 25.
Previously we have demonstrated that stromal interacting molecule-1 (STIM1) was involved in ethanol induced liver injury. However, the exact pathogenic mechanism of STIM1 in alcoholic liver disease (ALD) is still unknown. We constructed plasmid vectors encoding short-hairpin RNA against STIM1 to investigate its role in ALD in the rat liver cell line BRL and in Sprague-Dawley rats. The results showed that STIM1 targeted sh-RNA (Sh-STIM1) significantly ameliorated ethanol-induced BRL cells injury and liver injury in rats with 20 weeks-induced alcoholic liver disease. Inhibition of STIM1 also reduced intracellular calcium ion concentration, reactive oxygen species (ROS) production, lipid peroxidation, NF-kappa B activation and TNF-α production under ethanol exposure. STIM1 may play an important role in the pathogenesis of alcoholic liver disease. Silencing STIM1 may be effective in preventing alcoholic liver disease.
先前我们已经证明基质相互作用分子-1（STIM1）参与了乙醇诱导的肝损伤。然而，STIM1 在酒精性肝病（ALD）中的确切发病机制仍不清楚。我们构建了编码针对 STIM1 的短发夹 RNA 的质粒载体，以研究其在大鼠肝细胞系 BRL 和 Sprague-Dawley 大鼠中的作用。结果表明，STIM1 靶向 sh-RNA（Sh-STIM1）显著改善了乙醇诱导的 BRL 细胞损伤和 20 周诱导的酒精性肝病大鼠的肝损伤。在乙醇暴露下，STIM1 的抑制也降低了细胞内钙离子浓度、活性氧（ROS）产生、脂质过氧化、NF-κB 激活和 TNF-α产生。STIM1 可能在酒精性肝病的发病机制中起重要作用。沉默 STIM1 可能对预防酒精性肝病有效。
