| Background:There are many patients with liver diseases in China.For example,there were an estimated93million HBV carriers,and among them30million were patients with chronic hepatitis B. Accumulative5-year liver cirrhosis incidence is12%-15%in chronic hepatitis B patients.Liver fibrosis is a common pathological process to develop into cirrhosis in various chronic liver diseases and it is reversible.So we can seek effective treatments to slow liver fibrosis developing to cirrhosis or hepatic cellular cancer through exploring the effective methods to prevent or cure liver fibrosis.Multiple etiologies of liver disease lead to the deposition of increased and abnormal extracellular matrix,which is the hallmark of liver fibrosis.The activation of hepatic stellate cell (HSC) is generally considered to be a vital event in liver fibrosis,which results in deposition of a large deal extracellular matrix (ECM) in the liver,then fibrosis forms.During the process of liver fibrosis, with the deposition of ECM in Disse space,the fenestraes of liver sinusoidal endothelial cell(LSEC) gradually reduce or even disappear and subendothelial continuous basement membrane forms,which can be called sinusoids capillarization.Sinusoids capillarization is the important pathological mechanism of liver microcirculation dysfunction,which in turn can promote the development of liver fibrosis through various channels.Therefore we can seek effective drugs of liver fibrosis through studying how to prevent HSC activation and reverse sinusoids capillarization.Fuzhenghuayu(FZHY) decoction contains Sal via, Cordyceps sinensis,Walnuts,Gynostemma,Schisandra,Pine pollen,which is formulated on the basis of Chinese medicine theory"yu xue zu luo,zheng qi xu ruo".Pharmacological studies demonstrate that FZHY has a significant effect against post-necrosis liver fibrosis.The anti-hepatic fibrosis effects also had been observed from clinical trials.Our research term in the prophased studies had verified the effects of FZHY on HSC and LSEC from the cellular level and confirmed that FZHY decoction may resist liver fibrosis by down-regulating the secretion of ECM and inhibiting the proliferation of HSC and reversing sinusoids capillarization.But there is no report about the effects of FZHY on immunological liver fibrosis models.So our experiment studies the effects and mechanisms of FZHY on porcine serum-induced liver fibrosis,and provides more evidence for the application of FZHY decoction.We use interferon-y as positive control drug.Part1A study on the therapeutic effect of Fuzhenghuayu decoction on immunological liver fibrosis in ratsObject To study the effects of FZHY decoction on porcine serum-induced liver fibrosis in rats and the expression of a-SMA and desmin.Methods Fibrosis models was induced in rats by intraperitoneal injection with porcine serum for8weeks.Another normal control group was set up by intraperitoneal injection with physiological saline for8weeks.From the9th week, the model rats were randomly divided into model group,IFN-y group and FZHY group.IFN-y group and FZHY group were treated with IFN-y by intramuscular injection and FZHY by intragastric administration,respectively,at the same time both were treated with porcine serum by intraperitoneal injection. Normal group and model group were treated with porcine serum and physiological saline by intraperitoneal injection,respectively,at the same time both were treated with drink water by intragastric administration.At the end of12th week,the liver samples were subjected to:1.pathological sections for observing the changes of liver fibrosis by HE and MASSON staining;2.detected the expression of a-SMA and desmin by Western blot.Results1.Compared with the model group,the degree of liver fibrosis and fibrosis%were significantly lower in FZHY group,and the difference was significant (.P<0.01),but no significant difference between drug groups (P>0.05);2.Western blot showed that the expression of a-SMA and desmin in FZHY group is less than model group,and the difference was significant (P<0.01),but no significant difference between drug groups (P>0.05). Conclusion1.FZHY decoction could evidently relieve the degree of immunological liver fibrosis in rats;2.The expression of a-SMA and desmin and fibrosis%in FZHY group is down-regulated,which indicates that FZHY decoction could resist liver fibrosis by inhibiting action of HSC and down-regulating secretion of ECM.Part2Fuzhenghuayu decoction reverses sinusoids capillarization on rat fibrosis models induced by porcine serumObject To study the effects of FZHY decoction on sinusoids capillarization of liver fibrosis models induced by porcine serum.Methods The liver samples of part1were subjected to:1.detected the expression of vWF and CD31by Western blot;2.transmission electron microscopy observed the changes of the liver sinusoid structure and subendothelial basement membrane.Results1.Western blot showed that the expression of vWF and CD31in FZHY group is less than model group,and the difference was significant (P<0.05),but no significant difference between drug groups (P>0.05);2.Compared with the model group,the liver sinusoid stenosis and distortion and subendothelial basement membrane formation were alleviated in FZHY group,which indicates Fuzhenghuayu decoction could reverse sinusoids capillarization.Conclusion FZHY decoction could evidently relieve the degree of immunological liver fibrosis in rats by reversing sinusoids capillarization. |
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