Institute of Systems Biology and Bioinformatics, National Central University, Jhongli City 32001, Taiwan.
Evid Based Complement Alternat Med. 2012;2012:256561. doi: 10.1155/2012/256561. Epub 2012 Jul 2.
The incidence of cirrhosis is rising due to the widespread occurrence of chronic hepatitis, as well as the evident lack of an established therapy for hepatic fibrosis. In the search for hepatoprotective therapeutic agents, Graptopetalum paraguayense (GP) showed greater cytotoxicity toward hepatic stellate cells than other tested herbal medicines. Histopathological and biochemical analyses suggest that GP treatment significantly prevented DMN-induced hepatic inflammation and fibrosis in rats. Microarray profiling indicated that expression of most of metabolism- and cell growth and/or maintenance-related genes recovered to near normal levels following GP treatment as classified by gene ontology and LSM analysis, was observed. ANOVA showed that expression of 64% of 256 liver damage-related genes recovered significantly after GP treatment. By examining rat liver samples with Q-RT-PCR, five liver damage-related genes were identified. Among them, Egr1 and Nrg1 may serve as necroinflammatory markers, and Btg2 may serve as a fibrosis marker. Oldr1 and Hmgcs1 were up- and down-regulated markers, respectively. A publicly accessible website has been established to provide access to these data Identification of 44 necroinflammation-related and 62 fibrosis-related genes provides useful insight into the molecular mechanisms underlying liver damage and provides potential targets for the rational development of therapeutic drugs such as GP.
由于慢性肝炎的广泛发生以及肝纤维化缺乏既定的治疗方法,肝硬化的发病率正在上升。在寻找肝保护治疗剂的过程中,Graptopetalum paraguayense(GP)对肝星状细胞的细胞毒性大于其他测试的草药。组织病理学和生化分析表明,GP 治疗可显著预防 DMN 诱导的大鼠肝炎症和纤维化。微阵列分析表明,经基因本体论和 LSM 分析分类后,大多数与代谢和细胞生长和/或维持相关的基因表达恢复到接近正常水平。ANOVA 显示,256 个肝损伤相关基因中有 64%的表达在 GP 治疗后显著恢复。通过用 Q-RT-PCR 检查大鼠肝样品,鉴定了五个肝损伤相关基因。其中,Egr1 和 Nrg1 可作为坏死性炎症标志物,Btg2 可作为纤维化标志物。Oldr1 和 Hmgcs1 分别为上调和下调标志物。已经建立了一个公共可访问的网站,以提供对这些数据的访问。鉴定出 44 个与坏死性炎症相关的和 62 个与纤维化相关的基因,为肝损伤的分子机制提供了有用的见解,并为 GP 等治疗药物的合理开发提供了潜在的靶点。