Exploratory Study The Effect Of Artesunate On Hepatic Fibrosis

1.Objective:it was virus hepatitis,alcohol and Chemical toxicant that leaded to chronic inflammation of Hepar,it can be form hepatic fibrosis in post trauma hepatocyte,The attack rate accounted the whole chronic hepatitis 25%-30%,and it is ascending.year by year.the hepatic fibrosis would be develop hepatic cirrhosis and liver cancer,if it was treated,now the hepatic cirrhosis is presumed unreversible,the hepatic cirrhosis and liver cancer is the common disease and cause of a disease in our country.Otherwise the hepatic fibrosis can be reverse in earlier period,but it is not the specific treatment at present.Thus it is urg approach the block hepatic fibrosis medicine in earlier period.2.Empirical study2.1 MethodWe adopt CC14 causing the hepatic fibrosis model,to study and research the hepatic fibrosis mechanism of action to adopt pathology staining technique and specific stain and electron microscopy and immunohistochemistry and TUNNELand immunofluorescence technique and so on..2.2 Content2.2.1 The effection of the morphologyArtesunate that the Artesunate treat,the fibrosis.2.2.2 Artesunate experimental study of the TGF-β₁ and MMP-1and TIMP-1and ECM(typeâ… ,â…¢,â…£collagen)and Ca²⁺.2.2.3 Artesunate experimental study of the proliferating cell nuclear antigen(PCNA) 2.2.4 Artesunate experimental study of theapoptosis gene and Fas and Bcl-2 proteinum.2.2.5 Artesunate experimental study of cell proliferation path transferent PKC.3.result3.1 Artesunate is able to protected thehepatic cell.and Artesunate can prevent the fiber forming,depend on HE staining and specific stain and electron microscope proving.3.2 The Artesunate hold the balance of Ca²⁺inner hepatic cell..3.3 Among the case(normal and model Artesunate and control group),use of The Artesunate of high dose was significantly lower for the control subjects and model subjects(P＜0.01).the model subjects had higher maen Artesunate amd control subjects(P＜0.01).the Artesunate of low dose was similar between the model subjects(P＞0.05).The Artesunate of high dose was similar between the normal(P＞0.05).use of the Artesunate to traet hepatic fibrosis with TGF-β1 has some effect in some hepatic fibrosis mouse.3.4 Among the team(normal and model Artesunate and control team),use of The Artesunate of high dose was significantly lower for the control subjects and model subjects(P＜0.01).the model subjects had higher maen Artesunate amd control subjects(P＜0.01).use of the Artesunate to traet hepatic fibrosis with typeâ… andâ…¢andâ…£collagen has some effect in some hepatic fibrosis mouse.3.5.No significant difference in MMP-1 was found between among the group(P＞0.05).but we found significant effects of Artesunate on TIMP-1 outcome,use of The Artesunate of high dose was significantly lower for the control subjects and model subjects(P＜0.01).the model subjects had higher mean Artesunate and control subjects(P＜0.01).Artesunate for the treatment of hepatic fibrosis resulted in significant improvement in the activity MMP-1 and recovery the ratio MMP-1/TIMP-1and promotion degradation the collogen.3.6 the percentage of positive pcna findings in group model was significantly higher when compared with group normal(P＜0.01)and with group control(P＜0.01).pcna is the important signal of s stage in cyclin..the Artesunate can be hold-back CDKs and antiproliferative. 3.7the percentage of positive fas and Apoptosis gene findings in group high dose Artesunate were significantly higher when compared with group model(P＜0.01)and with group control(P＜0.01).but the percentage of positive bcl-2 findings in group high dose artesunate was significantly lower when compared with group model(P＜0.01)and with group control(P＜0.01).Artesunate for the treatment of hepatic fibrosis resulted in significant improvent in the express of fas and Apoptosis gene,in the same time the Artesunate for the treatment of hepatic fibrosis resulted in significant descend in the express of BCL-2.3.8 Artesunate for the HSC-T6 rssulted in transposition in the pkc,the outcome indicate d the Artesunate can inhibite the PKC transposition.,the Artesunate can inhibite the FAK-PI3K-Akt signal transduction path.4.conclusion4.1 Artesunate can protect the hepatic cell and keep Ca2+ in hepatic cell balance.4.2use of the Artesunate to treat hepatic fibrosis associated with TGF-β1 has some effect in fibrosis.The effect,however is less universal than the group model and group control.The artesunate can recovery the MMP-1/TIMP-1 balance.4.3 the Artesunate can hold back the CDKs and cause the cell cycle retention G1 stage。4.4the Artesunate nduced the HSC Apoptosis,the mechanism is the Artesunate can up-regulation the fas and down regulation bcl-2 gene.4.5 the Artesunate can inhibited the PDGF causing FAK-PI3K-Akt signal transduction.It can block the PKC transposition...