Expression Of Connective Tissue Growth Factor (CTGF) In Experimental Liver Fibrosis In Mice And The Inhibition Effects Of Anti-CTGF Antibodies On Liver Fibrosis

Hepatic fibrosis or hepatocirrhosis is one of the most important disease which is very harmful to human health. They are the outcome of gradually pathological changes for all kinds of hepatic disease. The main character of the diseases is the deposition of extra-cellularmatrix (ECM, mostly referred to collagen) because of its excess synthesis and decreased degradation. The initial phase is called hepatic fibrosis, and the severe phase is called hepatocirrhosis of which at this stage the re-configuration of the liver and the formation of pseudo lobules happened. Some immune media or cell factors (secreting from active hepatic stellate cell (HSC), damaging and regenerative hepatic cells, Kupffer cells, sinusoids endothelial cells, or natural killing cells , etc,) produced in a manner of autocrine or paracrine under the stimulation of inflammation or toxin, play biological effect by acting on the receptor of the target cells. The process of hepatic fibrosis formation is not still, but gradually. The most recently studies showed that hepatic fibrosis can be reversed under some circumstances, so the studies on the reverse factors of hepatic fibrosis will provide a clue to the explaination about the pathogenesis mechanism of hepatic fibrosis and hepatocirrhosis. The formation of hepatic cirrhosis is a complicated process in which multi-factor and multi-cell involved. Among them the cell factor net is the key point in most recent studies. Connective tissue growth factor (CTGF) which is newly discovered is regarded as the lower reaction element of the TGF-β1. Under the inducement of TGF-β1, CTGF is produced by interstitial cells, such as fibroblast, etc., and on the contrary, it can help TGF-β1 to take effects on interstitial cells, functioning as to accelerate proliferation of fibrous cells, and to participate the production and accumulation of ECM. All of that have been verified in many fibrosis diseases. In in vivo and in vitro's studies of hepatic fibrosis, CTGF can strongly regulate the proliferation of hepatic stellate cells, and its uncommon highly expression play an critical role in development of hepatic fibrosis, becoming the hotspot in hepatic fibrosis studiesThis experiment was based on hepatic fibrosis (CCl4) model in mice. The level of CTGF expression was determined by RT-PCR and immunohistochemistry in 38 experimental mice hepatic fibrosis, and also with comparison with collagen-Ⅰand collagen-Ⅲ, the expression changing of CTGF-mRNA in experimental hepatic fibrosis was detected so as to further explore its possible mechanisms. Another part of this study is to use CTGF-antibody and Oxymatrine for inhibition and treatment of mice hepatic fibrosis model whicht was newly established or established after 4 weeks. Compared with control group, CCl4 group or Radix Salviae Miltiorrhizar group, the serum biochemistry, liver function , oxidation and anti-oxidation , hydroxyproline level in liver cells, degree of pathology fibrosis, and the level of CTGF, collagen-Ⅰor collagen-Ⅲ were determined so as to provide the basic experimental data for the prevention and treatment of hepatic fibrosis in clinics.The results are as followings: (1) Expression level of CTGF-gene or CTGF protein in hepatic fibrosis of mice liver was markedly higher than that of control group (p<0.01). (2) Level of collagen-Ⅰor collagen-Ⅲ in liver tissue of all experimental mice groups was obviously higher than that of control group (P<0.05 ～ P<0.01).(3) Level of CTGF expression, collagen-Ⅰor collagen-Ⅲ was in line with the extent of mice hepatic fibrosis. The r value was 0.582,0.351,0.374, respectively. Among them relativity of CTGF with hepatic fibrosis was the most highest (P<0.01), then was collagen-Ⅰand collagen-Ⅲ (P<0.05).(4) The expression of CTGF was in direct proportion to the level of collagen-Ⅰor collagen-Ⅲ (comparing CTGF with COL-Ⅲ, Ｐ<0.05; comparing CTGF with COL-I, Ｐ<0.01). (5) The hepatic function: Compared with model group, hepatic function in groups treated with ALT, a...