ABSTRACT
Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract fromthat is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.
ABSTRACT
BACKGROUND:Pericytes, which are widely distributed in the microvasculature except lymphatic vessels, are not only a constituent of microvessels, but also play an important role in microvascular occurrence, development, stability, maturity and remodeling. Its signal transduction is currently a hot spot. OBJECTIVE:To review recent advances in the signal pathways related to pericytes and angiogenesis. METHODS:We retrieved PubMed database, Wanfang database, CNKI database and China Biology Medicine disc for articles addressing pericytes and angiogenesis published from 1994 to 2014. The keywords were “pricytes; endothelial cels; microvessels; signal transduction” in English and Chinese, respectively.RESULTS AND CONCLUSION:In the early stage of capilary formation, recruitment of pericytes contributes to the occurrence and development of new blood capilaries. However, in the late stage of angiogenesis, pericytes inhibit endothelial cel proliferation and promote endothelial cel differentiation, thereby promoting vascular maturation, maintaining normal structure and regulating their permeability. In this process, signaling pathways of platelet-derived growth factor B/platelet-derived growth factor receptor β, transforming growth factor β, angiopoietin-1/Tie-2, human heparin binding epidermal growth factor/ErbBs, and stromal cel derived factor 1α/CXCR4 play an important regulatory role in pericytes and angiogenesis.