Font Size: a A A

Therapeutic Effect And Active Mechanism Of Jiaweisan Rentang On The Hbv-Induced Chronic Hepatitis And Hepatic Fibrosis

Posted on:2010-06-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z C XiangFull Text:PDF
GTID:1114360275466073Subject:TCM clinical basis
Abstract/Summary:PDF Full Text Request
Liver fibrosis,is a reversible reaction after the chronic liver disease,and the inevitable development of the pathological process for the chronic liver disease to cirrhosis.At present, there hasn't ideal treatment for some chronic liver diseases.such as the virus hepatitis which caused by hepatitis B virus hepatitis. From the pathological change,the liver fibrosis is reversible, and liver cirrhosis is irreversible.China is a high incidence of viral hepatitis epidemic.According to recent statistics,it shows that China has more than 20 million patients with liver disease.The IN of liver fibrosis is very high in our country,so it is a serious healthy problem that the national people must treat to.Therefore,searching for an effective prevention and treatment, for liver fibrosis,is an urgent requirement of national people and have far-reaching significance and important social value.HB is caused by the hepatitis B virus(HBV).There have about 3 billion HBV carriers all around the world.The HBV carriers is easily to get the risk of liver fibrosis,liver cirrhosis and liver cancer than non-carriers.China is a high incidence of hepatitis B and have about 120 million HBV carriers.However,the obsolete clinical manifestations and the ignoring of hepatitis B to the majority of patients lead to the aggravate of this disease,even the occuring of chronic hepatitis and liver fibrosis. Chronic hepatitis(HBV-induced) is the caused the important factor of the causing of liver fibrosis.The simple treatment for liver fibrosis can not make it cured completely.even if the well treatment can not rule out the risk of relapse.Therefore, anti-liver fibrosis in chronic hepatitis should be treated as a whole,is the guarantee for the complete cure.The research for the mechanism of chronic hepatitis and liver fibrosis have been some progress all round the world in nowday.However,in the field of clinical treatment,it still can't achieve the significant progress.Add the efficacy of common drugs for liver fibrosis is beyond ideal,and the drug have some disadvantages,for exsample, the obvious side effects and the high cost.So researchers at home and abroad are trying to search for a drug which have the advantage, including the exact effect,cheap and the shortage of toxic side effects.in order to cure the majority of chronic hepatitis and liver fibrosis.This subject is selecting the JIAWEISANRENTANG as an experimental drug,used for chronic hepatitis and liver fibrosis research.The research adopted immunohistochemist-ry,cell culture,flow cytometry and RealTime-PCR technology for the teatment effect and mechanism of anti-chronic hepatitis and anti-hepatic fibrosis on DHBV model,autoimmune liver fibrosis in rats,HSC cells and 2.2.15 cells.It is supply the clinical and laboratory basis for the further development and application.1.Use the DHBV-positive subjects to research JIAWEISANRENTANG in their serum DHBV-DNA levels.The results showed that: the model group of duck serum DHBV-DNA levels,compared with the normal group were significantly different(P<0.01), JIAWEISANRENTANG extract high-dose,low-dose and high dose of alcohol extract of DHBV-DNA were significantly inhibited(P<0.05 or P<0.01),and JIAWEISANRENTANG small doses of alcohol did not extract a significant role in inhibiting DHBV-DNA.2.Used JIAWEISANRENTANG in the role of the 2.2.15 cells were observed on the 2.2.15 cells and HbsAg secretion HbeAg.The results showed that concentration of 1,0.5,0.25,0.125,0.625,0.3125 mg /mL of JIAWEISANRENTANG tothe secretion of HbsAg and HbeAg for 2.2.15 cell inhibition rate was 85.36%,79.72%,75.81%,69.65%, 62.14%,30.56%and 90.17%,83.26%,76.34%,46.86%,20.32%,0.36%. Drug dose and HbsAg and HbeAg show increased secretion of the relationship between inhibition rate,which increased with the dose of which drug to more pronounced inhibition of HbsAg.3.Observation JIAWEISANRENTANG on 2.2.15 cells,HBV-DNA expression.The results showed that with a flavored soup Sanren 2.2.15 cells inhibited the expression of the role of HBV,of which 1mg/mL,0.5mg/mL and 0.25mg/mL concentration JIAWEISANRENTANG extract more than the positive effect of the drug.4.Rat model of liver fibrosis by DMN was observed for the action to liver liver tissue HA,LN,IVC,PCIINP and the impact of HyP by JIAWEISANRENTANG.Model group and treatment group in serum HA, LN,IVC,PCIII and water HyP average increase compared with the normal group,the difference was significant(P<0.01). JIAWEISANRENTANG to large and small dose group compared with the model group,serum HA,PCIII,LN,CIV and HyP were significantly decreased(P<0.05 or 0.01),and the effect increased with the dose corresponding enhancement;JIAWEISANRENTANG alcohol extract of high-dose group compared with the model group,serum LN,IVC, PCIII and HyP level dropped to a certain extent,but no significant (P>0.05).JIAWEISAN-RENTANG low-dose group compared with the model group,serum PCIII,CIV,HyP levels decline,but no significant(P>0.05).Fufangbiejiaruanganpian serum HA,PCIII, CIV level than the model group was no significant difference(P>0.05).5.Observed the rat model of liver fibrosis which is induced by DMN insect JIAWEISANRENTANG on DMN hepatic fibrosis of rat liver tissue the effects of morphology:(1) HE staining;(2)α-SMA immunohistochemistry;(3) I type collagen immunohistochemistry. The experiments show that damage from hepatic loble,the formation of false lobules,hyperplasia of collagen fibers,such as objective changes in liver structure,the JIAWEISANRENTANG can reduce the extent of liver fibrosis and improve liver structure, the promotion of ECM degradation and thus the treatment of experimental liver fibrosis.6.Observed JIAWEISANRENTANG Decoction on rat liver tissue TGFβ1 and PDGF-B Inhibition of the expression.The results showed that the model group and treatment group in serum TGF-β1 and PDGF expression,and the normal group,the difference was significant (P<0.01).JIAWEISANRENTANG extract group were significantly inhibited TGF-β1 and PDGF expression(P<0.05),and superior to the positive drug,especially JIAWEISANREN-TANG mention the most obvious high-dose group(P<0.01),and dose effect with a corresponding increase in enhancement;JIAWEISANRENTANG ethanolic dose low-dose group compared with the model group,the TGF-β1 and PDGF inhibit the effect of the expression of significant (P<0.05).M JIAWEISANRENTANG decoction group compared with the model group,serum TGF-β1 on the impact of no significant(P<0.05).7.Observed JIAWEISANRENTANG Decoction on liver fibrosis serum TNF,IL-1 and the effects of IL-6.The results suggest that JIAWEISANRENTANG extract Sanren group have significantly lower serum TNF-α,IL-1,as well as the role of content(P<0.05 or P<0.01).Water extract of which high-dose group was superior to the positive effect of the drug group.The JIAWEISANRENTANG high-dose group in the serum TNF-αand IL-1 significantly reduced the role of IL-6 but no significant effect.While small doses of alcohol extracts of serum TNF-α,IL-1 and IL-6 had no significant effect.8.Discussion JIAWEISANRENTANG on HSC-T6 TIMP-1 and MMP-2 expression.The results showed that the concentration of 40mg/mL and 20mg/mL JIAWEISANRENTANG can effectively reduce the TIMP-1 and MMP-2mRNA level and decreased with lower concentrations.9.Observed of rat liver tissue and HSC in the Fas/FasL expression and flavored soup Sanren intervention role.Experiments found that JIAWEISANRENTANG significantly increase rat liver tissue and HSC Fas/FasL gene mRNA expression,and the water extract of the Fas /FasL are better than the increase in the role of drug-positive group. 10.Discussion on HSC apoptosis in vitro and JIAWEISANRENTANG intervention role.Experimental Tip:JIAWEISANRENTANG and Danshen injection can induce apoptosis of HSC,which JIAWEISANRENTANG extract 40mg/ml and 20mg/ml obvious apoptosis dose group,and better than Danshen injection group.In addition, the JIAWEISANRENTANG Decoction group to promote apoptosis of HSC is also a dose-dependent manner.11.Explore JIAWEISANRENTANG Decoction on liver fibrosis in rat tissue plasminogen activator inhibitor,tissue-type plasminogen activator impact.The results showed that:compared with the cells in the control group,JIAWEISANRENTANG adjustable uPA and PAI-1 expression.Which the concentration of 40mg/mL and 20mg/mL JIAWEISANRENTANG extracts of HSC-T6 cells,uPA and PAI-1 expression and regulation of better than other groups.In serum uPA and PAI-1 expression inhibition in JIAWEISANRENTANG group are better than other groups.
Keywords/Search Tags:HDBV model, DMN, 2.2.15 cell, HSC-T6 cells, Real-time PCR, Apoptosis
PDF Full Text Request
Related items