肝星状细胞论文：熊果酸对大鼠肝星状细胞NOX亚基p47(Phox)及其调控的下游信号通路的影响.docVIP

肝星状细胞论文：熊果酸对大鼠肝星状细胞NOX亚基p47(Phox)及其调控的下游信号通路的影响 【中文摘要】肝纤维化是肝脏慢性损伤后的一种普遍现象,最终导致细胞外基质(extracellular matrix, ECM)在肝脏中过度沉积。瘦素是一个重要的促肝纤维化因子,它与HSC上的Ob受体结合后,引起Janus激酶(Janus kinase,JAK)磷酸化及JAK-信号转导及转录激活因子(signal transducers and activators of transcription factor, STAT)的活化。JAK还通过激活 【英文摘要】Background:Hepatic fibrosis is a universal phenomenon of chronicity liver injury which eventually lead to the extracellular matrix deposition in the liver. Leptin is an important factor that can promote the liver fibrosis and cause phosphorylation of janus kinase (JAK) and JAK-signal transducers and activation of transcription factor (STAT) by binding with ob acceptor in HSCs. JAK activates reduced form of nicotinamide-adenine dinucleotide phosphate oxidase (NADPH oxidase, NOX) and the reduction-oxidation-sensitive cells signaling pathways Protein kinase B(AKT) and extracellular signal-regulated kinase (ERK) by generating reactive oxygen species (ROS). leading to the signaling cascade and gene expression related to the fibrosis and inflammation.Previously, we performed the study that Ursolic Acid (UA) could significantly improve liver tissue structure of hepatic fibrosis in vivo, and better than colchicine. It could inhibit the proliferation of HSCs and induce the apoptosis of HSCs in vitro. Pretreatment with UA could inhibit NOX subunit p22Phox and Racl mRNA and ROS induced by leptin and activation of nuclear factor-KB, and subsequently induce the apoptosis of HSCs. In this study, well observe effects of UA on NOX subunit p47pho and its downstream signaling pathway ERK1/2 induced by leptin in HSCs, and expression of collagen 1.:To explore the effects of UA on NOX subunit p47phox and its downstream signaling pathway ERK1/2 induced by leptin in HSCs(HSC-T6), and proliferation of HSCs and expression of ECM.Methods:HSC-T6 in the exponential growth phase were devided:normal control group; leptin (100ng/ml) treated; leptin treated together with UA (50μM); leptin treated together with JAK inhibito