Effect of bone marrow mesenchymal stem cells on the Smad expression of hepatic fibrosis rats

Objective:To investigate the impact of bone marrow mesenchymal stem cells on Smad expression of hepatic fibrosis rats.Methods:A total of 48 adult female SD rats were randomly divided into three groups,normal control group(n=10),observation group(n=19)with liver fibrosis model rats injected with BMSCs cells:model group(n=19),with liver fibrosis model rats injected with physiological saline.Serum index,TGF-β1 and Smad expression were detected.Results:TypeⅢprocollagen,Ⅳcollagen,hyaluronic acid,laminin levels of observation group were significantly lower than those of model group(P0.05).The content and expression of TGF-β1in serum and liver tissue of observation group were significantly lower than those of model group(P0.05).Compared with normal control group,the Smad3,Smad4 mRNA and protein expression of model group were significantly increased,the Smad7 mRNA and protein expression were significantly reduced(P0.05).Compared with model group.Smad3,Smad4 mRNA and protein expression of observation group were significantly reduced,and Smad7 mRNA expression were significantly increased(P0.05).Conclusions:BMSCs can regulate Smad expression to some extent,and reduce the degree of liver fibrosis.     

Treatment of pig serum-induced rat liver fibrosis with Boschniakia rossica, oxymatrine and interferon-α

AIM: To investigate the effect of Boschniakia rossica (BR), oxymatrine (OM) and interferon-alpha (IFN-α) 1b on the therapy of rat liver fibrosis and its mechanism. METHODS: By establishing a rat model of pig serum-induced liver fibrosis, liver/weight index and serum alanine transaminase (ALT) were observed to investigate the therapeutic effect of BR,OM and IFN-α. Radioimmunoassay was utilized to measure procollagen type Ⅲ (PCⅢ) and collagen type Ⅳ (CIV). RT-PCR was used to assay the expression of liver transforming growth factor- beta 1 (TGF-β1) mRNA. Immunohistochemistry of alpha-smooth muscle actin (α-SMA) and pathologic changes of liver tissues were also under investigation. RESULTS: Serum PCⅢ and CIV in BR, OM and IFN-α groups were significantly declined compared with those in model group, and their RT-PCR revealed that TGF-β1 mRNA expression was also reduced more than that in model group. Immunohistochemistry demonstrated that α-SMA also declined more than that in model group. Serum ALT in IFN-α, control and model groups was within normal level. Serum ALT in BR group had no significant difference from those of IFN-α, control and model groups. Serum ALT in OM group was significantly higher than those in BR, IFN-α, model, and control groups. CONCLUSION: BR, OM and IFN-α can prevent pig serum-induced liver rat fibrosis by inhibiting the activation of hepatic stellate cells and synthesizing collagen. OM has hepatotoxicity to rat liver fibrosis induced by pig serum.     

Treatment of pig serum-induced rat liver fibrosis with Boschniakia rossica, oxymatrine and interferon-α

AIM: To investigate the effect of Boschniakia rossica (BR), oxymatrine (OM) and interferon-alpha (IFN-α) lb on the therapy of rat liver fibrosis and its mechanism. METHODS: By establishing a rat model of pig serum-induced liver fibrosis, liver/weight index and serum alanine transaminase (ALT) were observed to investigate the therapeutic effect of BR, OM and IFN-α Radioimmunoassay was utilized to measure procollagen type Ⅲ (PCⅢ) and collagen type Ⅳ (CⅣ). RT-PCR was used to assay the expression of liver transforming growth factor- beta 1 (TGF-β1) mRNA. Immunohistochemistry of alpha-smooth muscle actin (α-SMA) and pathologic changes of liver tissues were also under investigation. RESULTS: Serum PCⅢ and CⅣ in BR, OM and IFN-α groups were significantly declined compared with those in model group, and their RT-PCR revealed that TGF-β1 mRNA expression was also reduced more than that in model group. Immunohistochemistry demonstrated that α-SMA also declined more than that in model group. Serum ALT in IFN-α, control and model groups was within normal level. Serum ALT in BR group had no significant difference from those of IFN-α, control and model groups. Serum ALT in ON group was significantly higher than those in BR, IFN-α,model, and control groups. CONCLUSION: BR, OM and IFN-α can prevent pig serum-induced liver rat fibrosis by inhibiting the activation of hepatic stellate cells and synthesizing collagen. OM has hepatotoxicity to rat liver fibrosis induced by pig serum.     

ACEI attenuates the progression of CCl_4-induced rat hepatic fibrogenesis by inhibiting TGF-β1, PDGF-BB, NF-κB and MMP-2,9

AIM: Angiotensin II has pro-fibrotic function in the liver. Blockade of the renin-angiotensin-aldosterone-system (RMS) attenuates hepatic fibrosis. The aim of the present study was to determine the mechanism of angiotensin-converting enzyme inhibitor (ACEI) on the progression of rat hepatic fibrosis. METHODS: Forty male Wistar rats were divided into three groups. Model group (Mo): The rats were injected subcutaneously with 40% of CCl4 0.25 mL/100 g. Perindopril group (Pe): The rats were injected subcutaneously with 40% of CCl4. Perindopril, equivalent to 2 mg/(kg·d), was administrated. Control group (Nc): the rats were treated with olive oil only. After 4 and 6 wk, the rats were killed. The liver sections were stained with Masson. The protein expressions of AT1R, TGF-β1 and PDGF-BB were examined by Western blot. Nuclear factor κB (NF-κB) DNA binding activity was examined by EMSA (Electrophoretic gel mobility shift assay). Matrix metalloproteinase-2,9 (MMP-2,9) activity was assessed by zymography. Serum laminin (LN) and hyaluronic acid (HA) were measured using radioimmunoassays. RESULTS: Using Western blot, we clearly provided direct evidence for the expression of AT1R in liver. The expression was up-regulated when fibrogenesis occurred. Perindopril treatment significantly reduced mean fibrosis score, protein levels of AT1R, TGF-β1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NPκB DNA binding activity markedly increased in model group, perindopril treatment considerably reduced NPκB DNA binding activity. CONCLUSION: Perindopril attenuates CCl4-induced hepatic fibrogenesis of rat by inhibiting TGF-β1, PDGF-BB, NF-κB and MMP-2,9.     

Effect of matrine on transforming growth factor β1 and hepatocyte growth factor in rat liver fibrosis model

Objective:To observe the preventive and control effect of matrine on transforming growth factor(TCF- β1) and hepatocyte.growth factor(HCF) of liver fibrosis tissue in rals.Methods:A total of48 SD rats were randomly divided into A,B,C,D groups with 12 in each,group A as the normal control group and groups B.C,D as liver fibrosis models using composite modulus method with carbon tetrachloride(CCL_4).Group B was the model group,group C adopted γ— interferon lavage therapy in the second day of modeling,and group D adopted matrine lavage treatment,at 4 and8 weeks after treatment.Six rats were executed for detection of TGF- β1 and HGF,liver tissue histology and comparison fibrosis degree changes of rat liver tissue between groups.Results:Croups B,C,D showed a more significantly increased TCF- β1 at each time point compared with group A(P0.05);Group B showed a more significantly increased TGF- β1 than groups C and D at weeks 4 and 8(P0.05);group D showed a lowest level of TGF-β1,followed by groups C and B.HGF of group B decreased more significantly than A group at weeks 4 and 8(P0.05);HGF of groups C and D was significantly elevated at 4 and 8 weeks than groups A and B(P0.05),in which the group D showed the highest level of HGF.According to tissue histologic observation,rat liver tissue structure of group A was clear and normal,tissue structure of group B was destroyed with obvious fibrous tissue hyperplasia and fatty change of hepatic cells;groups C and D showed a slighter liver tissue damage,cell necrosis and connective tissue hyperplasia in collect abbacy than group B with a trend of obvious improvement.Conclusions:Matrine can reduce TGF- β1expression and enhance the activity of HGF,so as to realize the inhibition effect on liver fibrosis in rats.     

Therapeutic effects and molecular mechanisms of anti-fibrosis herbs and selenium on rats with hepatic fibrosis

AIM:To study the therapeutic effects of anti-fibrosis herbsand selenium on hepatic fibrosis induced by carbontetrachloride (CCl_4) in rats and the underlining molecularmechanisms.METHODS:Fifty-three Wistar rats were randomly dividedinto:normal control group,model control group,colchicinegroup,anti-fibrosis herbs group (AF group) and anti-fibrosisherbs plus selenium group (AS group).The last four groupswere administered with CCl_4 at the beginning of experimentto induce hepatic fibrosis.Then colchicine,anti-fibrosis herbsand selenium were used to treat them.The normal controlgroup and the model control group were given normal salineat the same time.At the end of the 6~(th) week,rats in eachgroup were sacrificed.Blood and tissue specimens weretaken.Serum indicators (ALT,AST,HA,LN) were determinedand histopathological changes were graded.Lymphocyte CD_4and CD_8 were examined by flow cytometry.Expression ofTGF-β_1 and NF-κB was detected by immunohistochemistryand expression of TGF-β_1 mRNA was detected by semi-quantified RT-PCR.RESULTS:Histological grading showed much a smallerdegree of hepatic fibrogenesis in AS group and AF groupthan that in colchicine group and model control group.Theserum content of ALT,AST,HA and LN in AF group and ASgroup were significantly lower than that in colchicine group(ALT:65.8±26.5,67.3±18.4 and 96.2±20.9 in AF,AS andcolchicine groups respectively;AST:150.8±34.0,154.6±27.3and 215.8±24.6 respectively;HA:228±83,216±58 and416±135 respectively;LN:85.9±15.0,80.6±18.6 and106.3±14.2 respectively) (P<0.05).The level of CD_4 andCD_4/CD_8 ratio in AF group and AS group was significantly higherthat those in cochicine group (CD_4:50.8±3.8,52.6±3.4 and40.2±2.1 in AF,AS and colchicine groups respectively;CD_4/CD_8 ratio:1.45,1.46 and 1.26,respectively (P<0.05).The expression level of NF-κB and TGF-β_1 in the liver tissuesof AF and AS treatment groups was markedly decreasedcompared with that in cochicine group,and TGF-β_1 mRNAwas also markedly decreased (1.07±0.31 and 0.98±0.14 vs2.34±0.43,P<0.05).CONCLUSION:Anti-fibrosis herbs and selenium havebeneficial effects on hepatic fibrosis in rats by enhancingimmunity and inhibiting NF-κB and TGF-β_1 expressions.     

Role of TGF-β1/Smads pathway in carotid artery remodeling in renovascular hypertensive rats and prevention by Enalapril and Amlodipine

Objective To investigate the role of transforming growth factor-β1 (TGF-β1), Smad2/3 and Smad7 expressions in carotid artery remodeling in renovascular hypertensive rats, and also the therapeutic effect of Enalapril and Amlodipine. Methods The renovascular hypertensive rat (RHR) models with “two-kidney and one-clip” were established, including model group (n = 6), sham-operated group (n = 6), Enalapril group (10 mg/kg per day, n = 6), Amlodipine group (5 mg/kg per day, n = 6) and combination group (Amlodipine 2.5 mg/kg per day + Enalapril 5mg/kg per day, n = 6). The medication were continuous administrated for six weeks. Carotid artery morphological and structural changes in the media were observed by HE staining, Masson staining and immuno histochemical staining. Media thickness (MT), MT and lumen diameter ratio (MT/LD), and the expression levels of media α-smooth muscle actin (α-actin), proliferating cell nuclear antigen (PCNA), TGF-β1, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in carotid arteries were measured. Results The media of carotid arteries in RHR model group was significantly thickened, the volume of smooth muscle cell was increased, and the array was in disorder; MT, MT/LD, the proliferation index of smooth muscle cell and collagen fiber area percentage of carotid arteries in the model group were significantly higher than those in the sham-operated group (P < 0.01). Compared to sham-operated group, the model group had significantly higher expressions of TGF-β1 and p-Smad2/3 (P < 0.05) and lower Smad7 expression. Both Enalapril and Amlodipine improved smooth muscle hypertrophy and collagen deposition, reduced RHR carotid MT, MT/LD, proliferation index of smooth muscle cell, collagen fiber area percentage and the expressions of TGF-β1 and p-Smad2/3 (P < 0.05), increased Smad7 expression (P < 0.05). Moreover, the combination treatment of Enalapril and Amlodipine had significantly better effects than single Amlodipine group (P < 0.05), but not single Enalapril group. Conclusions TGF-β1/Smads pathway may participate in the mechanism of carotid artery remodeling in RHR; the role of Amlodipine and Enalapril in inversing carotid artery remodeling may be related to the change of TGF-β1/Smads pathway, the combination treatment of Amlodipine and Enalapril had better effects than single administration of Amlodipine.     

Effects of perindopril and valsartan on expression of transforming growth factor-beta-Smads in experimental hepatic fibrosis in rats

BACKGROUND: Previous studies have shown that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of hepatic fibrosis, and blockers of the RAS may be active as an antifibrogenic goal. However, the potential role of RAS inhibition on expression transforming growth factor (TGF)-beta-Smads in hepatic fibrosis remains unknown. The aim of this study was to investigate the effect and mechanism of an angiotensin-converting enzyme inhibitor (perindopril) and an angiotensin II receptor blocker (valsartan) on TGF-beta1 and TGF receptor II (TRII) mRNA, Smad3 and Smad7 in fibrotic hepatic livers in rats. METHODS: Sixty Wistar rats were randomly divided into four study groups (n = 15 for each group), including normal controls, hepatic fibrosis models, and two treated groups with either perindopril or valsartan, starting from the fourth week after being exposed to carbon tetrachloride (CCl(4)) for 4 weeks. The levels of TGF-beta and TRII mRNA in liver tissue were analyzed by RT-PCR. The expressions of TGF-beta1, Smad3 and Smad7 in liver tissues were evaluated by immunohistochemistry. The liver histopathology was examined by hematoxylin and eosin (HE) staining and by electron microscopy, respectively. The liver function and serum hyaluronic acid were also assayed by biochemistry and radioimmunoassay. RESULTS: Compared with the hepatic fibrosis models, the levels of TGF-beta1, TRII mRNA and the expression Smad3 significantly decreased in the two treated groups, and the expression of Smad7 was significantly increased in the liver of rats treated with perindopril or valsartan (P < 0.05 or P < 0.01). The histological changes and ultrastructure of fibrotic liver, liver function and hyaluronic acid also remarkably improved in the treated rats. CONCLUSIONS: The angiotensin-converting enzyme inhibitors perindopril and valsartan have a protective effect on liver injury and can ameliorate hepatic fibrosis in rats induced by CCl(4). The mechanisms may be associated with their effects of down-regulating TGF-beta1, TRII mRNA and smad3, and up-regulating Smad7.     

培哚普利和缬沙坦对肝纤维化大鼠TGF β1及其Ⅱ型受体mRNA与Smad3、7表达的影响

目的观察培哚普利和缬沙坦抗大鼠肝纤维化的疗效和对转化生长因子β1(TGFβ1)及其Ⅱ型受体(TGFβ1RⅡ)mRNA与Smad3、smad17的影响。方法大鼠随机分为止常对照组，模型组、培哚普利治疗组和缬沙坦治疗组。四氯化碳皮下注射诱导大鼠肝纤维化模型，治疗组于造模第4周开始分别予以培哚普利和缬沙坦灌胃。采用RT-PCR检测肝组织TGFβ1与TGFβ1RⅡ mRNA；免疫组织化学技术检测TGFβ1、Smad3及smad7在肝内的表达及定位，检测肝组织病理改变，检测肝组织羟脯氢酸和血清透明质酸。结果与模型组大鼠比较，经培哚普利或缬沙坦治疗大鼠肝内TGFβ1与TGFβ1RⅡ mRNA表达明显下降、以及smad3蛋白表达明显降低，而Smad7的表达增加。TGFβ1与Smad3的免疫阳性反应信号主要位于纤维间隔中的细胞浆，Smad7主要在肝细胞浆表达，上述物质在两种药物组之间表达差异无显著性。培哚普利或缬沙坦治疗后肝组织羟脯氨酸及血清透明质酸含量较模型组显著降低；肝小叶结构均趋于正常，纤维间隔明显变溥。结论培哚普利或缬沙坦均能有效地减轻肝纤维化大鼠的肝脏损伤及纤维化程度，其机制可能与直接或间接抑制肝内TGFβ1与TGFβ1RⅡ mRNA及Smad3表达，并促进Smad7表达有关。     

Effect of Losartan, an Angiotensin II Antagonist, on Hepatic Fibrosis Induced by CCl4 in Rats

In addition to regulating blood pressure and body fluid homeostasis, the renin-angiotensin system (RAS) is also involved in hepatic fibrogenesis. We aimed to investigate the effect of losartan, an angiotensin II (Ang II) antagonist, on CCl4-induced hepatic fibrosis in rats. Hepatic fibrosis was induced by a subcutaneous injection with 50% CCl4 in Sprague-Dawley rats. The amount of CCl4 administered was 1 mg/kg. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. Hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in culture supernatants of Kupffer cells (KCs) stimulated with Ang II was determined by ELISA. Liver samples collected after 12 weeks of CCl4 treatment were stained with hematoxylin and eosin, then scored. Losartan (2.5, 5, and 10 mg x kg(-1), ig) and captopril (100 mg x kg(-1), ig) significantly decreased liver and spleen indexes, serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological scores showed that losartan had an inhibitory effect on the progression of hepatic fibrosis. In in vitro experiments, losartan (1 x 10(-9) - 1 x 10(-5) M) significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of KCs, but captopril (1 x 10(-5) M) did not. The results showed that losartan significantly inhibited the progression of hepatic fibrosis induced by CCl4, and the inhibitory effect of losartan on hepatic fibrosis might be associated with its ability to inhibit the production of TNF-alpha and TGF-beta1 by activated KCs.     

ACEI attenuates the progression of CCl4-induced rat hepatic fibrogenesis by inhibiting TGF-β1, PDGF-BB, NF-κB and MMP-2,9

AIM: Angiotensin II has pro-fibrotic function in the liver. Blockade of the renin-angiotensin-aldosterone-system (RAAS) attenuates hepatic fibrosis. The aim of the present study was to determine the mechanism of angiotensin-converting enzyme inhibitor (ACEI) on the progression of rat hepatic fibrosis. METHODS: Forty male Wistar rats were divided into three groups. Model group (Mo): The rats were injected subcutaneously with 40% of CCl(4) 0.25 mL/100 g. Perindopril group (Pe): The rats were injected subcutaneously with 40% of CCl(4). Perindopril, equivalent to 2 mg/(kg.d), was administrated. Control group (Nc): the rats were treated with olive oil only. After 4 and 6 wk, the rats were killed. The liver sections were stained with Masson. The protein expressions of AT1R, TGF-beta1 and PDGF-BB were examined by Western blot. Nuclear factor kappaB (NF-kappaB) DNA binding activity was examined by EMSA (Electrophoretic gel mobility shift assay). Matrix metalloproteinase-2,9 (MMP-2,9) activity was assessed by zymography. Serum laminin (LN) and hyaluronic acid (HA) were measured using radioimmunoassays. RESULTS: Using Western blot, we clearly provided direct evidence for the expression of AT1R in liver. The expression was up-regulated when fibrogenesis occurred. Perindopril treatment significantly reduced mean fibrosis score, protein levels of AT1R, TGF-beta1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NF-kappaB DNA binding activity markedly increased in model group, perindopril treatment considerably reduced NF-kappaB DNA binding activity. CONCLUSION: Perindopril attenuates CCl(4)-induced hepatic fibrogenesis of rat by inhibiting TGF-beta1, PDGF-BB, NF-kappaB and MMP-2,9.     

核因子κB和转化生长因子β1在银杏叶提取物抗肝纤维化中的作用

目的观察银杏叶提取物（EGB）对大鼠肝纤维化的防治效果，探讨EGB抗肝纤维化的机制。方法采用四氯化碳诱导大鼠肝纤维化。EGB各组四氯化碳处理同模型组，另分别给予0．25、0．5、1．0g／kg EGB灌胃。8周末检测其肝功能以及血清透明质酸和层黏连蛋白。取肝组织进行氧化应激测定，免疫组织化学法检测核因子KB（NF-kB）P65和α-平滑且儿肌动蛋白的表达，逆转录聚合酶链反应法检测转化生长因子β1（TGF-β1）和Ⅰ型胶原mRNA的表达，凝胶电泳迁移率分析检测NF-kB的活性，并进行病理组织学检查。结果EGB组肝纤维化分级评分、肝功能以及血清透明质酸和层黏连蛋白较模型组明显改善；EGB能抑制氧化应激、肝星状细胞的活化、NF-kB P65的表达以及NF-kB活性。此外，EGB还可减低TGFβ1和1型胶原mRNA的表达。结论EGB可能通过抑制氧化应激和TGFβ1的表达，减弱NF-kB诱导的肝星状细胞活化，从而阻止四氯化碳诱导的大鼠肝纤维化的发生发展。     

Effects of AT1 receptor antagonist, losartan, on rat hepatic fibrosis induced by CCl(4)

AIM:To investigate effect of losartan, an AT1 receptor antagonist, on hepatic fibrosis induced by CCl(4); and to determine whether or not AT1 receptors are expressed on hepatic stellate cells. METHODS AND RESULTS:Fifty male Sprague-Dawley rats, weighing (180 plus minus20)g, were randomized into five groups (control group, model group, and three losartan treated groups), in which all rats were given the subcutaneous injection of 40% CCl(4)(every 3 days for 6 weeks) except for rats of control group. Rats of losartan-treated groups were treated with losartan (20 mg/kg, 10 mg/kg, 5 mg/kg, daily gavage). After 6 weeks liver tissue and serum samples of all rats were examined. Serum hyaluronic acid (HA), procollagen type III (PC III) were detected by radioimmunoassays. van Giesion collagen staining was used to evaluate the extracellular matrix of rats with liver fibrosis. The expression of AT1 receptors, transforming growth factor-beta (TGF-beta), and alpha-smooth muscle actinalpha-SMA) in liver tissue were determined by immunohistochemical techniques. Compared with model group, serum ALT and AST of losartan-treated groups were significantly reduced (italic>t = 4.20,P < 0.01 and italic>t = 4.57,P < 0.01). Serum HA and PC III also had significant differences (italic>t = 3.53,P<0.01 and t=2.20, P<0.05). The degree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors, TGF-beta, and alpha-SMA in liver tissue.CONCLUSION:AT1 receptor antagonist, losartan, could limit the progression of the hepatic fibrosis induced by CCl(4). The mechanism may be related to the decrease in the expression of AT1 receptors and TGF-beta, ameliorating the injury of hepatocytes; activation of local renin-angiotensin system might relate to hepatic fibrosis; and during progression of fibrosis, activated hepatic stellate cells might express AT1 receptors.     

阻断转化生长因子-β1信号传导治疗大鼠实验性肝纤维化

目的 观察腺病毒介导的反义Smad4基因阻断转化生长因子-β1(TGF-β1)信号传导后对肝纤维化的治疗作用。方法 将腺病毒介导的反义Smad4基因导入四氯化碳／乙醇诱导的大鼠纤维化肝脏，用RT-PCR及western方法观察Smad4的表达，并观察肝脏的病理变化和胶原表达。结果 纤维化肝脏中Smad4的表达较正常肝脏明显增强，Ⅰ型胶原增多。经转基因处理后大鼠纤维化肝脏中Smad4的表达明显弱于未治疗的纤维化肝脏，Ⅰ型胶原减少；且治疗组肝脏纤维间隔也明显减少，纤维化程度明显减轻。结论 腺病毒介导的反义Smad4基因能有效阻断TGF-β信号传导系统，减少细胞外基质的产生，从而减轻肝纤维化的程度。     

蓝莓对大鼠肝纤维化TGF-β1/Smads信号通路的影响

目的观察蓝莓对大鼠肝纤维化的预防作用及对肝纤维化大鼠肝组织转化生长因子（transforminggrowthfactor,TGF）-β1／Smads信号通路的影响。方法45只健康sD大鼠被随机分为正常对照组、模型组、蓝莓预防组、丹芍化纤胶囊预防组、蓝莓＋丹芍化纤胶囊预防组。每组9只。用四氯化碳（cch）制作大鼠肝纤维化模型,共8周。测定肝脏指数及血清ALT、AST并进行肝组织病理学检查,采用实时荧光定量RT—PCR检测TGF-β1、Smad4mRNA的表达,免疫组织化学法检测肝脏组织TGF-β1、Smad4及Smad7蛋白的表达。结果与正常对照组比较,模型组TGF-β1及Smad4的表达增高（P〈0．05）,而Smad7的表达降低（P〈0．05）。与模型组比较,各预防组血清ALT及AST均明显降低（P〈0．05）,TGF-β1及Smad4的表达均降低（P〈0．05）,而Smad7的表达均增高（P〈0．05）。结论蓝莓对GEL所致大鼠肝纤维化有一定的预防保护作用,其机制可能与蓝莓影响TGF-β1／Smads信号转导通路,从而下调TGF-β1及smad4的表达,同时上调Smad7的表达有关。