| Present view , repeated chronic damage to the liver can result proliferation and differentiation of hepatic stellate cells finally cause excess proliferation and doposit of ertracellular matrix (ECM) ,cause fibrosis and cirrhosis. Fibrosis is the stage of cirrhosis and is a recoverable pathologic change..Despite numerous studies on the development of hepatic fibrosis,the mechanism remains unclear this experiment wished to clarily the mechanisms through morphological and biochemical study of the early stages of hepatic fibrosis induced by low does of Dimethylnitrosamine in the rat .Method : male rats of the Wistar strain ,divude into five groups randomly ie: control group and four treatment groups. treatment groups were used for the induction of liver injury.DMN (10ul/kg body weight ,i.p.) was given 3 consecutive days a week for 4 weeks to wistar rats.controls received an equivalent amount of saline.the animals were sacrificed on days 7 , 14 , 21 and 28 . the body weight and liver weight of rats in earch group were measure .the changes of hepatic stellate (HSCs),hepatic endothelial cell,hepatic kupffer cell,hepatic pit cell, hepatocyte,Serum Hyaluronic Acid (HA), serum typeIV collagen and Laminin (LN) in different periods of LF were observed variation using light microscope,electron microscope,Immunohistochemical ,Histochemical methods. The result were statistically evaluated using spss10.0analysis .The results: An increase in liver weight was observed by the 7th of DMN treatment , with a decreased liver weight by the 28th days .The maximum liver and body weight ratio increased on the 14th day , but it the decrease on 28st day . Light and electron microscopy: DMN-tread rats showed evidence of hemorrhagic necrosis, mainly centrolobular was evident on the 7day , showing disruption of sinusoidal lining and disappearance of the space of Disse invaded by and large and small mononuclelar cells , the extent of parenchymal damage was characterized under the election microscope and included alterations of the sinusoidal wall with formation of large gaps between endothelial cells and enlarged perisinusoidal paces containing erythrocytes orhrombocytes ocasional 'Pit cells'.plenty of liver kupffer cells appeared in the period and enhanced the ability of releasing inflammatory factor.with time, fibrotic septa were associated with cells bearing transitional features between those of hepatic stellate cells , myofibroblasts and fibroblasts , some pit cells apparently gained access into the space of Disse through large openings of the endothelial wall and were found closely apposed to the hepatocytes, all rats showed micronodular fibrosis in the hepatic parenchyma , electron microscopy showed alterations of the sinusoidal wall the presence of numerous erythrocytes in the spaces of Disse.At day 28 , there was observed in all rats similar findings in the hepatic parenchyma, under the electron microscope, fibrous septa contain abundant collagen bundles , extended segment of the sinusoidal wall were still deprived of endothelium and fibrous septa contained large myofibroblasts and fibroblast , sinusoidal capilarization.Immunohistochemical stain method : For the simultaneous detection of alpha smooth muscle actin(a-SMA),as a maker of activated Hepatic stellate cells(HSCs) in controls, a-SMA positive cells were detected mainly in the portal space either as elements of vascular walls or as fibroblast-like cells scattered in the connective tissue or finely apposed to bile ductudes.A significant increase of a-SMA positive cells was observed already at 7thday after the DMN injection.these cells showed an elongated fibroblast-like shape and.their number progressively increased throughout the experiments,reaching a maximum at 28th day using five-grade classified statistics to analyse the extent of hepatic fibrosis ,there was significant difference between control group and DMN groups(P<0.05) betweenDMN groups there were significant difference too. Histochemical stain method : Tiss...
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