| Background and Objective Liver fibrosis is common outcome of chronic liver injury of variable origin, as well as a key process leading to cirrhosis. Fibrosis results from the interaction of many cytokines and Extra Cellular Matrix (ECM), among them, TGF β1 is the most active cytokines that stimulate both the activation of Hepatic stellate cell (HSC), the production of ECM, the suppress of collagen enzyme and the activation of collagen enzyme inhibitor. The activation of HSC is the key process in liver fibrosis. It was demonstrated that almost in all kinds of pathological liver fibrosis, proliferation and activation of HSC was shown , and new receptors and genes expressed by HSC was found, ECM and cytokines were greatly produced in autocrine and paracrine manner. HSC expresses TGFβ receptor(TβR), and TGF β1 can activate TβR type I (TβR-I ) though the combination with TβR type II(TβR-II). It has been shown that Smad protein is discovered the only substrate of TGFβ1. Activated TβR-I stimulates Smad3, one of the single molecular in SMADs family, then transmits the signal into cell nuclear. However, Smad7 antagonizes the role of Smad3 by binding to receptor. As there is limitation of modern medicine in treatment of liverfibrosis, the study of Chinese traditional medicine is regarded as effective way to treat liver fibrosis. It has been shown that DiKang capsule mainly consisting of Sanqi & peach nutlet & lecithin , is effective in treatment of liver fibrosis. To investigate the mechanisms of DiKang capsule in rat liver fibrosis model induced by different dose of Dimethylnitrosamine (DMN). This study analyzed the pathological changes of live tissues and serum level of collagens, expression of TR-II on HSC, and mRNA expression of both smad3 and Smad7 in HSC. Methods: 46 Wasta male rats were divided into five groups at random. Rats in group 1(10 rats) intraperitoneally(i.p.) injected with l0mg/kg of DMN for three weeks (three times a week), rats in groups2(10 rats)i.p. injectd 5mg/kg of DMN for six weeks. Rats in group3(10 rats) were fed wuth the DiKang diet lml(a concentration of 30g/l per rat once a day)for 3 weeks after the administration of DMN treated the same as group 1 .Rats in group 4 (10 rats) were i.p. injected with 5mg/kg of DMN for 6 weeks, 3 weeks after the begin og administration of DMN, at the same time rats were daily fed with DiKang diet for 3 weeks(lml/day/rat).Rats in group 5 (6 rats) were i.p. injected with 9% sodium chloride solution instead of DMN.Liver tissue of those 5 groups of rats were sectioned onto slice and stained with HE/Siruis red/Masson stain. Histological the changes of liverwere examined.Procollagen-HI-peptide (P-III-P), collagen IV(C-IV), hyaluronic acid (HA) in serum of those 5 groups of rats were detected by ELISA methods.Expression of TR-II on in vitro cultured HSC isolated from livers was assayed by flow cytometry (FCM).The mRNA expression of Collagen-III/smooth muscle actin (SMA)/ Smad 3/ Smad 7 was analyzed by srmi-quantitative RT-PCR with GAPDH as the control. Results were shown as ratio of target products over GAPDH.Results: Histological examination of liver showed that administration of DMN(group 1 and goup 2) induced serious damages as well as fibrotic changes. In contrast, the damage and fibrosis reduced significatly in therapeutic groups (group3 and group4).The serum concentration of P-III-P in rats from group 1 and group 2 were significantly higher than that in normal control (group 5), whereas the serum concentration of P-III-P in rats from therapeutic groups(group 3 and group 4) were lower than that in group 1 and group 2.The expression of TR-II on HSC and ratio of TpR-II positive HSC from group 3 was higher than that form group 1. And The expression of TR-II on HSC and ratio of TR-II positive HSC from group 4 has no changed(P>0.05) compared with group 2.The expression of Smad3 mRNA in rats fed with DiKang capsule diet (group 3 and group 4)was lower than that in rats not being fed with the diet (group land group2). But t...
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