| Objective: hepatic fibrosis is a dynamic process and pathology whichcan developing to cirrhosis by various chronic liver disease, it’s the result ofliver fibre connective tissue over sedimentation. Liver fibrosis is self recoveryreaction of organism to chronic damage, based on the feature of liverextra-cellular matrix hyperplasia and sedimentation, blood capillarization andhepatic lobule fibrosis is shown in the hepatic sinus, liver function slack up,hyperpiesia of portal vein, such as splenomegaly, ascites… in the functionality,even worse, it develops to liver cancer and influences patients quality of lifeseriously, therefore, treatment in time and blocking the further development ofliver fibrosis is significant. Lots of cell factor participated in the generationand development of liver fibrosis, PDGF is a strongest cell factor currentlywhich promotes the HSC increase and differentiation. It irritates increase,moving and inversion to the myofibroblast of HSC strongly, inducing thegeneration of collagen, sedimentation is significant in the liver fibrosisdevelopment. The researchers at home and abroad conducted a mass of studiesfor the liver fibrosis, but blocking of liver fibrosis is still difficult in clinical,recently, Using the Chinese traditional medicine to prevent the liver fibrosisindicates the certain advantage and great potential in clinical as well as baseresearch. Chinese traditional medicine Biejiajianwan comes from Jinguiyaoluewhich wrote by Zhang zhongjing, it promotes the blood circulate, removingthe blood stasis, using the gentle method and force, attack the virus andreplenish the body both together, and covered all. Demonstrated by a greatnumber of experiment, Biejiajianwan as a kind of Chinese traditional medicinehas the function for liver fibrosis complex pathogenesis via muti-pathway and muti-target spots to anti the liver fibrosis. This researchh will take thesubcutaneous injection of CCL4method for SD mouse to establish the liverfibrosis mouse module, Biejiajianwan, which promote the blood circulate andremove the blood stasis is put in use to interpose for the model. Observing thegeneral situation of experiment animal, inspect the content of LN, Col-IV, ALT,AST, ALP, ALB. Observing the liver nosology shape, inspecting liver tissuelevel of PDGF, liver tissue Ras/extracellular signal regulated kinase，ERK1,discuss the prevent function and possible affective principle of Chinesetraditional medicine which promote the blood circulate and remove the bloodstasis. It provide the experiment basis to cure the Ganji cause byextravasated blood blocking, upright deficient which defined as basicpathogeny.Methods:48healthy male SD rats, weighted280-320g, after raising oneweek, split to6groups: control, model,the western medicine group,Biejiajianwan low dose treated, middle dose treated, high dose treated. Exceptthe control group, every rats of other groups will be injected the40%CCL4peanut oil5mL/Kg in the subcutaneous from the first day, then, inject3ml/kgevery3days, meanwhile, Biejiajianwan0.55g/（kg.d）,1.1g/（kg.d）,2.2g/（kg.d）will be given to stomach for every Chinese traditional medicine lowdose,middle dose and high dose group except the western medicine group, thecolchicin0.3mg/kg will be given to the stomach for western medicine group,once per day. At the beginning of the forth weekends, execute the rats in themodel randomly, and observe the liver nosology change, the modelsuccessfully created after sixth week from experiment. Then, medicine will begiven to the stomach of rats in each Chinese medicine group for five weeks,once per day. The distilled water is put into the stomach of rats in model groupfor11weeks. The same quantity of Peanut oil is shot to the subcutaneous ofrats in control group and distilled water is put into the stomach, once per day,at the total of6weeks, after6weeks, stop the peanut oil injection and putdistilled water in the stomach for5weeks. At the end of11thweek, abrosia12hours, arteria cruralis Blood Sampling are separated, measuring the serum ALT, AST, ALP, ALB level, detect the serum LN, Col-IV level, according toradioimmunoassay, take the liver, put the liver tissue in the4%paraformaldehyde, dyed by HE and Masson, observe liver nosology change ofmouse in each group, then,preserve the liver tissue in the refrigerator with-80degree after quick-freezing by the liquid nitrogen, inspect the content of PDGF,Ras protein level in the liver tissue in accordance with reversetranscription-polymerase chain reaction RT-PCR.Results:1General condition of experimental ratsDuring the experiment, the death happened in each group except thecontrol group,3rats dead in model group,1dead in high dose medicinetreated,2in low dose treated group and middle dose treated group,3inwestern medicine group. The weights of rats in the control group areincreasing, regulate diet, quickly react, bright eye, smoothly hair. Thecondition of the rats in other groups are poor, slow in reacting, loose hair anddamp, dull color, some of the rats in the model group blind and bad temper,skinny figure.2The pathology changes of the rat,hepatic tissue in different groupIn the normal group, integrate diolame, light red color, smooth and tidysection. hepatic lobule structure clear, most of the liver cell are mononuclear,strip liver surface, liver cell shows radial pattern and surround the center vein.Regarding on the model group, the shape of liver is abnormally, coarse surface,feels like the sand particle. Liver cell become swell and getting bigger, most ofcells thanatosis, the vessels expanded and inflammation cells found, thestructure of liver lobule damaged, fibers connective tissue in the veins area hasobvious hyperplasia, the liver lobule is surrounded to different size of livercell bunches and take shape to pseudolobule. The liver lobule in the each doseof Chinese medicine group which can promote the blood circulate and removethe stasis has clear structure. Liver sinus expand slightly, liver cells necrotic.fibers connective tissue in the veins area has moderate hyperplasia, theformation of pseudolobule decreasing distinctly, the liver nosology change of western medicine group is in the middle of western group and Chinesemedicine group. Note: the medicine which promote the blood circulate andremove the stasis improves the liver fibrosis level in the liver fibrosis rats, andfunction better than western medicine colchicines.3The levels of ALT, AST, ALP, and ALB in the serum of different groupsThe level of ALT, AST and ALP in the serum of different groups display:compared with normal group, the content of ALT, AST, ALP in the rats serumincrease obviously （P<0.05） in model group, western medicine group andChinese medicine low dose group and Chinese medicine middle dose group,and there were no significant differences between the normal group andChinese medicine high dose treated group （p>0.05）. Compare with modelgroup, the serum ALT, AST, ALP content decrease obviously （P<0.05） in eachChinese medicine group and western medicine group. Compare with westernmedicine group, serum ALT, AST, ALP content decrease obviously （P<0.05）in Chinese medicine high dose treated group, more content in the Chinesemedicine low dose treated group（P<0.05）, there is no meaning to comparewith Chinese medicine middle dose treated group（p>0.05）. compare in eachgroups of Chinese medicine group, the serum ALT、AST、ALP content mostthan others in low dose group, and the serum ALT、AST、ALP content lest thanothers in high dose group, the middle dose group in the middle place, distinctdiscrepancy exist in each Chinese medicine dose group （P<0.05）, Note: theChinese traditional medicine which promote the blood circulate and removethe stasis can decrease serum ALT, AST, ALP level of live fibrosis rats,improve the treatment of liver fibrosis.The level of ALB in the serum of different groups display: comparedwith normal group, the serum ALB declined obviously （P<0.05） in modelgroup, western medicine group, Chinese medicine low dose treated group andmiddle dose treated group, and there were no significant differences betweenthe normal group and Chinese medicine high dose treated group （p>0.05）.compared with model group, serum ALB content increase obviously （P<0.05）in western medicine group, Chinese medicine high dose treated group and middle dose group, There isn’t any meaning to compare discrepancy withChinese medicine low dose treated group. compared with western medicinegroup, serum ALB content increase obviously in Chinese medicine high dosetreated group, serum ALB content level decrease （P<0.05） in Chinesemedicine middle dose treated group, there isn’t any meaning to compare withmiddle dose group. there is discrepancy existing among each Chinesemedicine group serum ALB level. There into, high dose treated has the mostserum ALB content, middle dose group follows in second place, low dosetreated group has the lowest content （P<0.05）, Note: the medicine whichpromote the blood circulate and remove the stasis can turnaround the serumALB level decreasing trend, and improve the treatment for liver fibrosis.4The levels of LN and Col-IV in the serum of different groupsThe rats serum LN, Col-IV content indicates: compare with normal group,rats serum LN, Col-IV content in model, western, Chinese medicine low doseand middle dose increase obviously （P<0.05）,, and there were no significantdifferences between the normal group and Chinese medicine high dose treatedgroup （p>0.05）. compare with western medicine, the serum LN, Col-IVcontent decrease obviously （P<0.05） in the Chinese medicine high dose treatedgroup, higher content level in low dose medicine group （P<0.05）, no meaningto compare the discrepancy with middle dose treated group（p>0.05）. compareamong each dose medicine treated group, serum in Chinese medicine low dosetreated group has highest LN, Col-IV content, high dose group has lowestcontent and middle dose group in the middle place, the obvious discrepancyexisting in each dose treated medicine group（P<0.05）.The conclusion indicatesthat Chinese traditional medicine which promote the blood circulate andremove stasis can decrease the liver fibrosis serum LN, Col-IV content, maybethis is one of the method which treat liver fibrosis.5The levels of PDGF mRNA and Ras protein mRNA in the hepatic tissue ofdifferent groupsLiver tissue PDGF mRNA, Ras mRNA content indicates: compare withnormal group, the content of PDGF mRNA, Ras mRNA increased （P<0.05） in each group, thereinto, model group has the highest content, Chinese medicinelow dose group follows, western medicine, middle dose group at the middleplace, high dose group has the lowest content （P<0.05）. compare with themodel group, PDGF mRNA, Ras mRNA is shown as lower content in the livertissue, compare with western medicine, no meaning to compare thediscrepancy with Chinese medicine middle dose group（P>0.05）. compareamong each dose Chinese medicine group has the statistics meaning（P<0.05）,thereinto, low dose has the highest content, middle dose follows, liver tissuehas lowest PDGF mRNA, Ras mRNA content in the Chinese medicine highdose treated group.6The ERK1content of liver tissue in each group indicationIn the normal group, ERK1in liver tissue shows slight positive andyellow color, especially surround center vein of liver lobule, manifold, andDisse chamber, ERK1in the cytoplasm of liver star shape cells observed byhigh-power microscope, liver cells aren’t shown; regarding on the modelgroup, ERK1in the liver tissue increasing, enhance, ERK1as star shape andstrip shape is shows as positive surrounding the center vein and in the liverlobule，positive ERK1is shown in the area of the liver star cytoplasm andnucleus observed by high-power microscope, in western medicine and eachChinese medicine group, positive dyeing degree is decreased obviously,dyeing degree of interstitial cell between fibro and inflammatory cells positivedecrease, quantity of ERK1positive cells decrease, thereinto, ERK1has thelowest positive in Chinese medicine high dose group, and the highest positivein Chinese medicine low dose group, and no meaning to compare amongwestern and Chinese medicine middle dose. Note: the Chinese medicine whichpromote the blood circulate and remove stasis can decrease the PDGF mRNAcontent in the liver tissue and decrease the mRNA in the Ras protein obviously,decrease the ERK1in the rats liver tissue, improve the capability of anti liverfibrosis, maybe this is one of methods to cure liver fibrosis.Conclusions:1The Chinese traditional medicine which promote blood circulate and remove the stasis can improve the general situation of rats liver fibrosis, andimprove the liver function.2The Chinese traditional medicine which promote the blood circulateand remove the stasis can improve the rats liver fibrosis level, it’s a welltreatment for liver fibrosis.3The Chinese traditional medicine which promote blood circulate andremove the stasis can decrease the serum LN, Col-IV levels, decrease thesedimentation in the liver Disse, therefore, decrease the accumulation of ECM,maybe this is one of methods to cure liver fibrosis.4The Chinese traditional medicine which promote blood circulate andremove the stasis can decrease the PDGF mRNA and Ras protein mRNA inthe liver tissue of liver fibrosis, decrease the ERK1in the rats liver tissueobviously, improve the capacity anti liver fibrosis via activateRas/ERK1/2signal transmit route to achieve this, maybe this is one of themethods to prevent liver fibrosis. |
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