大黄酸抑制四氯化碳诱导的大鼠肝纤维化形成

目的:观察大黄酸对实验性肝纤维化的影响.方法:采用60％的四氯化碳(CCl_4)及5％的乙醇制备肝纤维化动物模型,分别用小剂量、大剂量大黄酸(25 mg/kg,100 mg/kg体重)干预,测定血清丙氨酸氨基转移酶(ALT)、透明质酸(HA)、Ⅲ型前胶(PC-Ⅲ)及肝组织丙二醛(MDA)含量,免疫组化方法观察转化生长因子 β1(TGF-β1)、α平滑肌肌动蛋白(α-SMA)的表达情况,并观察肝组织胶原面积及病理变化.结果:大黄酸组较模型组:(1)血清ALT、HA、PC-Ⅲ水平及肝组织中MDA含量显著降低(P<0.01);(2)肝组织中TGF-β1,α-SMA的表达显著减少(P<0.05或P<0.01);③肝组织胶原面积明显减少,纤维化程度明显改善(P<0.05或P<0.01).结论:大黄酸具有保肝作用和抑制肝纤维化作用,其作用机制可能与其抗炎、抗氧化作用及抑制HSC活化、抑制TGF-β1作用有关.     

Inhibitory effect of leflunomide on hepatic fibrosis induced by CCl4 in rats

AIM: To study the effect of leflunomide on CC14-induced hepatic fibrosis in rats. METHODS: Hepatic fibrosis was induced by subcutaneous injection with 50 % CCl4 in Sprague-Dawley rats. The amount of CC14 administered was 1 mg/kg. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. The transforming growth factor-β1(TGF-β1) in serum was determined by ELISA. The nuclear factor-kappa B (NF-κB) in liver tissue was examined by immunohistochemistry. Liver samples collected after 12 weeks ofCC14 treatment were stained with hematoxy-lin and eosin. RESULTS: Leflunomide (1, 3, and 9 mg/kg) significantly decreased indices of liver and spleen, the serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological examination showed leflunomide had inhibitory effect on fibrogenesis and formation of pseudolobulus. Furthermore, leflunomide significantly inhibited NF-κB expression in liver tissue, and reduced elevated serum TGF-κB and NO levels in rats of hepatic fibrosis. CONCLUSION: Leflunomide showed inhibitory action on hepatic fibrosis induced by CC14 in rats.     

Protection by and anti-oxidant mechanism of berberine against rat liver fibrosis induced by multiple hepatotoxic factors

1. The aim of the present study was to investigate the effect and mechanism of berberine, an alkaloid extracted from the traditional Chinese medicine coptis, on rat liver fibrosis induced by multiple hepatotoxic factors. 2. Male Wistar rats were separated into five groups, a normal control group, a fibrotic control group and fibrotic groups treated with three different doses of berberine. The fibrotic models were established by introduction of multiple hepatotoxic factors, including CCl(4), ethanol and high cholesterol. Rats in the treatment groups were administered 50, 100 or 200 mg/kg berberine, intragastrically, daily for 4 weeks. Serum levels of alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST), hepatic activity of superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) and hepatic hydroxyproline (Hyp) content were determined. Liver biopsies were obtained for histological and immunohistochemical studies to detect the expressions of alpha-smooth muscle actin (SMA) and transforming growth factor (TGF)-beta1. 3. The results showed that, compared with the fibrotic control group, serum levels of ALT and AST and hepatic content of MDA and Hyp were markedly decreased, but the activity of hepatic SOD was significantly increased in berberine-treated groups in a dose-dependent manner. In addition, histopathological changes, such as steatosis, necrosis and myofibroblast proliferation, were reduced and the expression of a-SMA and TGF-b1 was significantly downregulated in the berberine-treated groups (P < 0.01). 4. These results suggest that berberine could be used to prevent experimental liver fibrosis through regulation of the anti-oxidant system and lipid peroxidation.     

N-乙酰半胱氨酸对实验性肝硬化大鼠肝纤维化与脂质过氧化的影响

目的:探讨N-乙酰半胱氨酸(NAC)对肝硬化大鼠的作用及其影响肝纤维化与脂质过氧化损伤的机制。方法:雄性Wistar大鼠36只,随机分成正常组(7只)、模型组(14只)、NAC组(15只)。以10μL·kg~(-1)剂量二甲基亚硝胺(DMN)腹腔注射,每周连续3d,每日1次,共4 wk,诱导大鼠肝硬化模型。成模后,NAC组以NAC 0．1 g·kg~(-1)灌胃,每日1次,共4 wk;模型组给予等量生理盐水灌胃。HE染色与天狼猩红染色观察肝组织炎症与胶原沉积;水解法测定肝组织羟脯氨酸含量;生化法检查血清肝功能指标[丙氨酸转氧酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)、清蛋白(Alh)等],肝组织超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量;Western印迹法检测肝组织α-平滑肌肌动蛋白(α- SMA)与热休克蛋白47(HSP47)表达。结果:治疗4 wk后,模型组大鼠死亡7只,NAC组死亡3只, NAC明显提高肝纤维化大鼠的生存率(P＜0．01)。与正常组相比,模型大鼠肝脏肝细胞变性、坏死明显,炎性细胞浸润,胶原沉积并形成假小叶;血清ALT、AST和TBil升高,AIb下降;肝组织羟脯氨酸与MDA含量升高,SOD活性下降(P＜0．01)。而NAC可显著减轻肝脏炎症、肝细胞坏死与肝组织胶原沉积,改善模型大鼠异常的肝功能指标,降低肝组织羟脯氧酸与MDA含量,提高SOD活性(P＜0．05,P＜0．01),抑制模型大鼠肝组织HSP47与α-SMA蛋白的表达(P＜0．01)。结论:N-乙酰半胱氨酸有良好的治疗肝硬化作用,其作用机制与促进肝纤维化逆转及抗肝脏脂质过氧化有关。     

棓丙酯对大鼠肝纤维化防治作用的实验研究

目的观察棓丙酯对四氯化碳导致的肝纤维化大鼠的保护作用,为临床治疗肝纤维化提供实验依据。方法以四氯化碳皮下注射复制大鼠肝纤维化模型,设立正常对照组、肝纤维化模型组和棓丙酯组,棓丙酯组在造模的同时给予棓丙酯注射液皮下注射。6周后取肝组织常规HE染色观察肝脏病变,天狼猩红胶原染色、肝组织羟脯氨酸(HYP)含量测定观察肝纤维化程度;赖氏法测定血浆丙氨酸氨基转移酶(ALT);TBA法检测肝组织丙二醛(MDA)水平,产色基质偶氮法鲎试剂定量测定血浆内毒素。结果棓丙酯与肝纤维化模型组比较,①肝脏的损伤性改变较轻,肝组织HYP及肝纤维化指数(FI)明显降低。②血浆内毒素含量、ALT及肝组织MDA均有不同程度的降低。结论棓丙酯具有一定的抗肝纤维化的作用。     

木犀草素对四氯化碳致大鼠肝纤维化的保护作用及其机制研究

目的观察木犀草素对四氯化碳(CC l4)致大鼠肝纤维化的保护作用。方法用CC l4复制大鼠中毒性肝纤维化模型,观察木犀草素对大鼠血清中透明质酸(HA)、层黏蛋白(LN)、丙氨酸氨基转移酶(ALT/GPT)、天冬氨酸氨基转移酶(AST/GOT)、总蛋白(TP)、白蛋白(A lb)、肝组织病理学及超氧化物歧化酶(SOD)、丙二醛(MDA)、羟脯氨酸(Hyp)的变化;MTT比色法检测木犀草素对大鼠肝星状细胞(HSC)和人肝星状细胞(Lx-2)的增殖的影响。结果与模型组比较,木犀草素给药组血清学指标(HA、LN)明显降低(P<0.05),ALT、AST减少,TP、A lb升高,病理组织学检查明显改善,肝组织内SOD升高,MDA、Hyp降低,并对HSC、Lx-2细胞的增殖有抑制作用(P<0.05)。结论木犀草素对CC l4致大鼠肝纤维有较好的保护作用,其机制可能与抑制肝内胶原合成、降低自由基生成、减轻脂质过氧化及抑制HSC增殖活化有关。     

芍芪多苷抗大鼠免疫性肝纤维化作用及部分机制

目的探讨芍芪多苷(SQDG)抗大鼠免疫性肝纤维化的作用并对其机制作初步研究。方法建立人白蛋白致免疫性肝纤维化大鼠模型,设立正常对照组、模型组、SQDG给药组(42.5、85、170mg.kg-1)和阳性对照秋水仙碱组(Col0.1mg·kg-1)。HE染色对肝脏组织作病理检查。分光光度法检测血清中转氨酶活性和肝匀浆中丙二醛(MDA)含量、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性、羟脯氨酸(Hyp)含量;放免法检测血清中透明质酸(HA)、Ⅲ型前胶原(PCⅢ)水平;3H-Pro参入法检测SQDG对转化生长因子-β1(TGF-β1)刺激的肝星状细胞(HSC-T6)胶原合成的影响。结果SQDG对升高的血清转氨酶有降低趋势,但差异无显著性;病理组织学检查发现,SQDG可降低免疫性肝纤维化大鼠的纤维化程度,与模型组相比,纤维沉积、肝小叶的破坏等均有所减轻。SQDG还可降低肝纤维化大鼠肝组织Hyp含量,降低血清中HA和PCⅢ含量。进一步研究发现,SQDG降低肝纤维化大鼠肝匀浆中MDA的含量,升高抗氧化酶SOD、GSH-Px活性,改善肝脏氧化状态。SQDG(20～160mg·L-1)体外给药还可明显降低HSC-T6的3H-Pro参入量。结论SQDG具有明显的抗肝纤维化作用,其机制可能与其清除自由基、提高抗氧化物酶的活性和抑制HSC的胶原合成有关。     

雷公藤红素对二乙基亚硝胺诱导的大鼠肝纤维化的治疗作用及机制

目的观察雷公藤红素(Celastrol,Cel)对二乙基亚硝胺(DEN)诱导大鼠肝纤维化的治疗作用及机制。方法采用DEN诱导大鼠肝纤维化模型,分为正常对照组、模型组、Cel给药组(2、4、8 mg.kg-1)和秋水仙碱组(Col,0.1 mg.kg-1)。紫外分光光度法检测各组大鼠血清中AST、ALT、肝组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及肝组织中丙二醛(MDA)、羟脯氨酸(HYP)的含量;ELISA检测大鼠血清中透明质酸(HA)、层粘蛋白(LN)、Ⅲ型前胶原(PCIII)、Ⅳ型前胶原(CIV)、TGF-β1的含量;Western blot检测肝脏α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(ColⅠ)和TGF-β1蛋白的表达;HE染色观察肝组织病理形态学变化;Masson染色观察肝组织中胶原沉积变化。结果与模型组比较,Cel能明显降低肝纤维化大鼠血清中升高的TGF-β1、ALT、AST、HA、LN、PCIII含量,降低肝组织中升高的HYP和MDA的含量,明显升高肝组织中SOD和GSH-Px酶活性,减少肝纤维化大鼠肝组织中α-SMA、Col I和TGF-β1的表达,改善其肝脏病理损伤程度,减少肝脏中胶原沉积。结论 Cel对肝纤维化大鼠有很好的治疗作用,其作用机制可能与Cel的抗氧化作用,降低TGF-β1的表达,抑制HSC活化,抑制胶原合成有关。     

谷胱甘肽复方注射液治疗猪血清致大鼠肝纤维化的药效研究

 目的：研究谷胱甘肽复方注射液（CGII）治疗猪血清致大鼠免疫性肝纤维化的药效作用。方法：建立猪血清诱导免疫性肝纤维化模型,全自动生化仪检测血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、白蛋白（A）及球蛋白（G）水平;酶免法检测血清中透明质酸（HA）的含量;称取肝脏湿重,计算肝脏指数;消化法检测肝组织羟脯氨酸（Hyp）含量;苏木素-伊红（HE）及Masson染色处理肝脏组织切片;光镜观察病理学改变。结果：在猪血清诱导的大鼠肝纤维化模型中,所有剂量水平的CGII（2.7,5.4,10.8 mg?kg-1,im）能显著降低大鼠血清ALT,AST,A/G值和HA水平;中、高剂量CGII（5.4,10.8 mg?kg-1,im）能显著降低大鼠肝组织Hyp含量,明显改善肝脏病理组织状况;高剂量CGII（10.8 mg?kg-1,im）能显著降低大鼠肝脏指数。结论：CGII对猪血清致大鼠肝纤维化有治疗作用。     

人工虫草菌丝及锌减少肝纤维化大鼠肝脏胶原的沉积

目的观察人工虫草菌丝及葡萄糖酸锌对大鼠四氯化碳实验性肝纤维化肝内胶原沉积的作用.方法用四氯化碳制造雄性Wistar大鼠肝纤维化模型,根据在动物饮水中加入不同药物分为小剂量人工虫草组、大剂量人工虫草组、葡萄糖酸锌组、对照组,并设正常组(不造模).12周后处死动物进行检测.结果造模的4组动物肝脏质量及血清丙氨酸转氨酶(ALT)水平高于正常组,体质量增长低于正常组(均P＜0.05或P＜0.01),人工虫草组及葡萄糖酸锌组动物肝脏羟脯氨酸含量低于对照组(均P＜0.05).病理结果证实对照组肝纤维化程度重于各治疗组.人工虫草组动物尿量多于葡萄糖酸锌组(均P＜0.01).结论人工虫草菌丝和葡萄糖酸锌均可减少大鼠四氯化碳实验性肝纤维化肝内胶原的沉积,机制有待进一步研究.     

苦参碱对实验大鼠肝纤维化的影响

目的 :研究苦参碱对实验大鼠肝纤维化的防治作用 ,并探讨其可能的机制。方法 :应用四氯化碳诱导大鼠实验性肝纤维化 ,以苦参碱防治。观察3,6 ,12wk时溶剂对照组、四氯化碳组、苦参碱组血清丙氨酸转氨酶 (ALT)、透明质酸 (HA)、肝组织羟脯氨酸 (HyP)含量以及肝脏病理变化。结果 :苦参碱能显著减轻实验大鼠肝细胞变性、坏死及纤维组织的形成 ,同时能降低不同实验阶段血清ALT(P <0 .0 1) ,HA(P <0 .0 1)以及肝组织中HyP含量 (P <0 .0 5)。结论 :苦参碱有保护肝细胞 ,减轻肝细胞坏死 ,防治四氯化碳诱发的肝纤维化的作用。     

Effect of Sho-saiko-to extract on hepatic inflammation and fibrosis in dimethylnitrosamine induced liver injury rats

Sho-saiko-to extract, a Chinese herbal medicine, is widely used for treatment of chronic hepatitis in Japan. However, it is not clear what conditions Sho-saiko-to extract improves hepatic inflammation and fibrosis. We therefore induced various stages of liver injury in model rats and administered Sho-saiko-to extract. We then evaluated the liver inflammation and liver fibrosis-improving effects of Sho-saiko-to extract. The liver injury model rats were produced by administration of various doses of dimethylnitrosamine (DMN) and Sho-saiko-to extract was administered to these rats. Then the liver inflammation and fibrosis-improving effects of Sho-saiko-to extract were evaluated according to L-asparate aminotransferase (AST), L-alanine aminotransferase (ALT), liver retinoid levels, levels of hydroxyproline, Transforming Growth Factor-beta (TGF-beta), and the liver fibrosis area. These indicators depended on the total doses of DMN. The ability of Sho-saiko-to extract to improve liver inflammation and fibrosis was limited to the following levels of the respective parameters: AST levels (234-264 U/l), ALT levels (208-232 U/l), TGF-beta levels (1102-1265 pg/g liver tissue), hydroxyproline levels (633-719 nmol/g liver tissue), and liver fibrosis area (9.7-10.6 times for normal rat). These findings suggested that Sho-saiko-to extract is effective in the treatment of liver inflammation and fibrosis up to a certain degree of severity, but it produces no improvement in more severe cases.     

J—911对实验性肝损伤的保护作用

通过建立小鼠急性肝损伤及大鼠慢性肝损伤模型,观察并研究海洋药物Ｊ－９１１对小鼠急性肝损伤及大鼠慢性肝损伤的保护作用。结果表明,Ｊ－９１１能明显降低Ｄ－半乳糖胺引起急性肝损伤疡血清ＡＬＴ升高和四氯化碳引起的急性肝损伤小鼠的血清ＡＬＴ、ＡＳＴ的升高,明显减轻模型肝组织病理损伤。     

姜黄素衍生物对四氯化碳诱导肝纤维化的治疗作用

目的:探讨姜黄素衍生物(Curc-OEG)对四氯化碳诱导肝纤维化的治疗效果。方法:以四氯化碳诱导形成大鼠肝实质损伤性肝纤维化模型。大鼠分为正常对照组(A组)、模型组(B组)、低剂量组(C组)、中剂量组(D组)、高剂量组(E组)、秋水仙碱组(F组)。除A组外,各组给予四氯化碳和橄榄油混合液皮下注射,2次/周,4周后B组给予生理盐水尾静脉注射,C、D、E组分别给予25、50、100mg.kg-1.d-1的Curc-OEG尾静脉注射,F组给予0.1mg.kg-1.d-1秋水仙碱灌胃。10周后测定肝功能及肝组织羟脯氨酸(Hyp)含量;做肝脏HE和天狼星红染色;定量PCR法测金属蛋白酶抑制因子-1(TIMP-1)、金属蛋白酶-13(MMP-13)基因的表达,Western Blot法测CollagenⅠ蛋白的表达。结果:与模型组比较,中、高剂量组ALT、AST明显降低(P<0.05),羟脯氨酸及CollagenⅠ蛋白表达明显降低(P<0.05),MMP-13 mRNA明显上调(P<0.05),以及TIMP-1 mRNA明显下调(P<0.05),并且HE及天狼星红染色结果也观察到肝脏炎症及纤维化程度明显减轻。结论:Curc-OEG能减轻四氯化碳诱导的大鼠肝纤维化。     

丹参滴丸对二甲基亚硝胺诱导大鼠肝纤维化的治疗作用

目的观察丹参滴丸对二甲基亚硝胺诱导的大鼠肝纤维化的治疗作用。方法除对照组外,其余大鼠采用ip二甲基亚硝胺4周诱导大鼠肝纤维化,造模结束后,ig丹参滴丸175、350、700 mg/kg,设扶正化瘀胶囊为阳性对照组(1 500 mg/kg),对照组、模型组给予同体积蒸馏水,1次/d,连续给药4周。末次给药后1 h剖杀动物,测定血清生化(ALT、AST活性及TP、ALB、TBIL含量)、血清胶原(HA、LN、Ⅲ型前胶原、IV型胶原)水平、肝组织中蛋白、Hyp的含量。取肝组织固定,进行HE、Masson染色,镜下观察肝细胞组织结构和肝纤维化程度。结果丹参滴丸能够显著增加血清中TP和ALB水平,降低ALT、AST活性和TBIL水平;能显著降低LN、Ⅳ型胶原含量,明显降低HA含量,对Ⅲ型前胶原含量有一定的降低趋势;肝匀浆检测显示能显著增加肝组织中蛋白含量,对Hyp含量有一定的降低趋势;肝组织病理学HE染色和Masson染色显示,丹参滴丸能够改善弥漫性肝细胞变性、坏死及炎症反应,能显著抑制胶原增生、减轻肝纤维化程度。结论丹参滴丸能显著改善大鼠的肝功能、减少肝组织纤维的增生、对二甲基亚硝胺诱导的大鼠肝纤维化有一定的治疗作用。     

Hepatoprotective effects of phloridzin on hepatic fibrosis induced by carbon tetrachloride against oxidative stress-triggered damage and fibrosis in rats

The present study was to study the hepatoprotective effects of phloridzin (PHL) on hepatic fibrosis induced by carbon tetrachloride (CCl?) in rats, on the basis of this investigation, the possible mechanism of PHL was elucidated. Male Sprague Dawley (SD) rats were randomly divided into six groups: control, model, PHL-L, PHL-M, PHL-H and colchine. All rats except control group were intraperitoneally injected with CCl?, and control rats were injected with olive oil, twice a week for eight weeks. At the same time, the rats were orally given homologue drugs once a day, respectively. Hepatoprotective effects of PHL were evaluated by liver weight indexes, biochemical values, total antioxidant capacity and total-superoxide dismutase, histopathological observations, hepatic fibrosis, and the hepatic fibrosis relative gene and protein expressions. PHL significantly improved hepatic function; remarkably decreased serum hyaluronic acid (HA), transforming growth factor-β1 (TGF-β1), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and liver tissues hydroxyproline, malondialdehyde (MDA) levels, increased glutathione peroxidase (GSH-Px), total-antioxygen capacity (T-AOC) and total-superoxide dismutase (T-SOD) contents of liver tissues; Real-time polymerase chain reaction (PCR) and immunohisto-chemical results showed PHL might markedly reverse the up-regulated mRNA and protein expressions of the α-smooth muscle actin (SMA), TGF-β1 and tissue inhibitor of metalloproteinase-1 (TIMP1), up-regulate the matrix metalloproteinase-1 (MMP1) mRNA and protein expressions. Histopathological observations provided supportive evidence for biochemical analyses and the hepatic fibrosis relative gene and protein expressions, and with the dose of PHL increasing, the aforesaid improvement became more and more strong. The studies demonstrated that PHL exerted beneficially hepatoprotective effects on hepatic fibrosis induced by CCl?, mainly enhancing antioxidant capacity of liver organizations, reduce the level of lipid peroxidation induced by CCl?, and protect hepatocyte membranes from damage, and alleviate hepatic fibrosis.     

Antifibrotic effects of the methanol extract of Polygonum aviculare in fibrotic rats induced by bile duct ligation and scission

The antifibrotic effect of the methanol extract from Polygonum aviculare (PA), Artemisia capillaris (AC) and an aqueous solution of biphenyl dimethyl dicarboxylate (DDB) on liver fibrosis were studied. Liver fibrosis was induced by a bile duct ligation and scission (BDL/S) operation, duration of 4 weeks in rats. In BDL/S rats, the levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin in serum and hydroxyproline content in liver were dramatically increased. The PA treatment in BDL/S rats reduced the serum AST, ALT and ALP levels significantly (p<0.01). Liver hydroxyproline content in PA treated BDL/S group was also reduced to 40% that of BDL/S control group (p<0.01). The morphological characteristics of fibrotic liver, which appeared in BDL/S control group were improved in the PA treated BDL/S group. But neither AC nor DDB treatment improved any parameters in fibrotic rats induced by BDL/S. These results indicate that PA has an antifibrotic effect on fibrotic rats induced by BDL/S.     

成纤维细胞激活蛋白在肝纤维化模型大鼠肝组织中的动态表达

目的:观察大鼠肝纤维化形成过程中成纤维细胞激活蛋白(fibroblast activation protein, FAP)的动态表达变化特点。方法:Wistar雄性大鼠分为正常对照组和模型组。模型组ip 0.5%二甲基亚硝胺复制肝纤维化模型, 于造模1、2、3周分别收集肝组织标本, 造模4周后处死大鼠, 收集血清和肝组织标本。全自动生化仪测定丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、谷氨酰转肽酶(GGT)和白蛋白(ALB), HE、天狼猩红染色观察病理形态, 试剂盒测定肝组织羟脯氨酸;real-time PCR和western blotting法检测肝组织FAP基因和蛋白表达。结果:模型组肝功能较正常组明显下降, 组织病理形态学和羟脯氨酸测定显示模型组肝损伤明显, 纤维化形成。real-time PCR和western blotting显示FAP基因和蛋白随造模时间延长表达逐渐增高。结论:FAP伴随大鼠肝纤维化模型形成逐渐增加, 与肝纤维化形成密切相关。     

坎地沙坦对肝纤维化大鼠血管紧张素转化酶2表达的影响

目的旨在观察血管紧张素Ⅱ1型受体拮抗剂(ARB)坎地沙坦对四氯化碳(CCl4)大鼠肝纤维化模型的疗效及大鼠肝组织血管紧张素转化酶2(ACE2)表达的影响。方法 42只雄性Wistar大鼠随机分为3组,正常对照组12只,模型组15只,坎地沙坦治疗组15只。除对照组外,给予大鼠首次皮下注射40%CCl4油剂5mL/kg,以后每次皮下注射40%CCL42mL/kg,每周2次。正常对照组给予相同剂量的油剂皮下注射。预防治疗组从实验第1天开始给予坎地沙坦(4mg.kg-1.d-1)灌胃,直至实验结束,共8周。分别于42d(6周)及56d(8周)时,测定各组体质量和门脉压力后,分别杀死6只大鼠,留取血及肝组织标本备用。分离血清测丙氨酸氨基转移酶(ALT),通过苏木素-伊红(HE)及Masson染色观察各组肝纤维化的程度,采用免疫组织化学染色测定ACE2表达情况。结果与对照组相比,模型组体质量降低(P<0.05),血清ALT升高(P<0.05),而预防治疗组体质量增加,ALT水平下降,差异有统计学意义(P<0.05),模型组门脉压力升高,与对照组比较差异有统计学意义(P<0.05),治疗组的门脉压力下降(P<0.05)。ACE2免疫组织化学结果表明:与正常对照组相比,模型组肝组织中ACE2阳性表达增强(P<0.05),坎地沙坦治疗组ACE2表达较模型组明显增高(P<0.05)。结论血管紧张素(Ang)Ⅱ1型受体拮抗剂坎地沙坦具有良好的抗肝纤维化作用,其机制是坎地沙坦可增加肝组织ACE2表达,激活ACE2-Ang-(1-7)-Mas轴,促进Ang-(1-7)的生成增多,从而发挥其抗肝纤维化的作用。     

育阴软肝颗粒剂对大鼠肝纤维化的治疗作用

目的　研究育阴软肝颗粒剂对大鼠肝纤维化及其阴虚证的治疗作用。方法　采用多因素复制肝纤维化动物造模,通过观测大鼠肝纤维化指标(ALT、AST、肝指数、肝组织病理学、羟脯氨酸及胶原蛋白等)与阴虚指标(进食与饮水量、自主活动、体重、cAMP、cGMP等),研究育阴软肝颗粒剂对实验性肝纤维化大鼠的防治作用。结果　6.2~24.8g·kg-1 剂量范围内的育阴软肝颗粒剂能降低纤维化大鼠血清ALT、AST及肝指数,降低肝组织羟脯氨酸及胶原蛋白的含量,缓解肝组织纤维化病理学变化;同时,育阴软肝颗粒剂能降低肝纤维化大鼠的饮水量,增加体重,减少活动次数与站立次数,降低cAMP及cAMP/cGMP,缓解阴虚症状。结论　多因素复制的肝纤维化大鼠模型有一定的阴虚症状;育阴软肝颗粒剂对肝纤维化及其阴虚证有一定的防治作用。