| Hepatic fibrosis is the common pathological foundation of chronic hepatic diseases and the essential pathological phase to cirrhosis. The main pathological characteristic of hepatic fibrosis is the increased deposition of newly formed extracellular matrix (ECM), resulting from a shifted balance between collagen synthesis and degradation. Though the pathogenesis of diverse hepatic diseases is different, the ultimate approach to liver fibrosis is similar. The activation of hepatic stellate cells (HSCs) plays a pivotal role in this process. The activation and proliferation of HSCs, which are the major source of ECM, are the crucial event to liver fibrosis. The increasing research has indicated that the activation and proliferation of HSCs were related with the inhibition of apoptosis. Nuclear factor-κB (NF-κB) bears the inhibiting effect on many sorts of cells,therefore, it has become one of the hotspots at the present time.NF-κB is a ubiquitous transcription regulation factor that plays a central role in preventing multiple cells from apoptosis. It can be activated by a variety of physiological and nonphysiological stimulating signals relevant to pathophysiology to generate genes transcription. NF-κB isinactive in quiescent HSCs, but its activity sustains in actived HSCs. Thus, we have justification to make it believed that NF-κB is likely to make the number of HSCs steady by inducing its apoptosis, eventually leading to hepatic fibrosis. As the inducible transcription regulation factor, the binding sites of NF-κB could accept immune stimuli such as tumor necrosis factor α (TNFα), lipopolysaccharide(LPS), interleukin-1(IL-1), or T cell activation. Except for immune stimuli, other factors as if ultraviolet irradiation, ionization radiation, inflammatory cytokines, growth factors, as well as bacteria and virus infection also could activate NF-κB. A great deal of those can stimulate NF-κB by way of inducing oxidation stress, for this reason reactive oxygen intermediates (ROIs) play an important role in stimulating NF-κB. Pyrrolidine dithiocarbamate (PDTC) functions due to two structural features: direct scavenging of ROIs by the dithiocarboxy group, and chelating activity for heavy metal ions that may catalyze formation of ROIs. As a result, PDTC could antagonize the activity of NF-κB effectively and induce HSCs apoptosis.Up to now, activation of NF-κB regulateing the expression of many genes involved in inflammatory, immune, proliferative and apoptotic responses has been reported, but few studies have addressed NF-κB in proliferation and apoptosis of HSCs. Hence, we set aboutour research from NF-κB, through experiments in vivo and in vitro, increased expression of NF-κB during hepatic fibrogenesis and induction of apoptosis with pyrrolidine dithiocarbamate in TNFα-stimulated HSCs were studied. The experiments contained two parts as below: Part One: Increased expression of NF-κB during hepatic fibrogenesis in bile duct ligation ratsObjective: To explore the dynamic expression of NF-κB in hepatic fibrogenesis. Methods: The Sprague Dawley rats were divided into two groups at random: sham operation group and model group(bile duct ligation,BDL). Livers in model group were harvested at fixed time points: 1wk,2wk,3wk and 4wk after operation. Livers in sham operation group were harvested at 4wk after operation. Histopathological changes were evaluated by hematoxylin and eosin staining, and by Masson's trichrome method. The distributions of NF-κB in the livers were assessed immunohistochemistrically. Expression of NF-κB protein was examined using Western blotting analysis.Results: ①Western blotting analysis displayed: NF-κB protein expressed in normal rat livers as well, they were up-regulated with model course, and the contents of them were the highest at week 4 after operation. NF-κB protein content of the rat livers in model groups at week 1 to 4 decreased by 17.41%, 27.47%, 66.03% and 89.87%,respectively. ②Immunohistochemistry techniq...
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