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。     

四氯化碳致大鼠肝纤维化及红苓肝宝的防治作用

目的：研究红苓肝宝对大鼠肝纤维化的防治作用，方法：运用皮下多次注射四氯化碳致大鼠慢性损伤性肝纤维化模型，观察红苓肝宝对大鼠肝组织病理变化。血清透明质酸，血清丙氨酸氨基转移酶（ALT／GPT），天冬氨酸氨基转氨酶（AST／GOT），总蛋白（TP）和白蛋白（Alb)以及内脏器官重量的影响，并与秋水仙碱进行了比较。结果：红苓肝宝在该剂量下大鼠肝纤维化率为45％，而模型组与秋水仙碱肝纤维化率分别为100％和50％，对肝损伤的其他指标观察表明，红苓肝宝对肝损伤的其他指标均有降低作用，与模型组比较，P＜0．01，结论：红苓肝宝在该剂量下对大鼠有明显的抗肝纤维化作用。     

胆宁片对实验性急慢性肝损伤的保护作用

目的：研究胆宁片对实验性小鼠急性肝损伤预防作用，及对大鼠慢性肝损伤的预防和治疗作用。方法：分别用D-氨基半乳糖和四氯化碳复制小鼠急性肝损伤和大鼠慢性肝损伤模型，检测小鼠和大鼠血清谷草转氨酶（AST）和谷丙转氨酶（ALT）的改变，观察胆宁片对大鼠血清总蛋白、白蛋白、A／G的影响、同时观察肝脏病理学改变。结果：胆宁片可明显抑制D-氨基半乳糖和四氯化碳引起的ALT、AST升高（P〈0．05或P〈0．01）；可显著升高四氯化碳引起的血清总蛋白和白蛋白含量降低（P〈0．05或P〈0．01）；肝脏病理组织学检查显示胆宁片可减轻肝细胞脂肪变性程度和纤维化程度。结论：胆宁片对小鼠D-氨基半乳糖急性肝损伤有较好的保护作用，对四氯化碳所致大鼠慢性肝损伤有一定的预防及治疗作用。     

生姜油治疗大鼠肝纤维化实验研究

目的研究生姜油对肝脏的保护作用。方法通过皮下注射四氯化碳复制慢性肝纤维化模型,观察生姜油的抗肝纤维化作用。采用比色法测定丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、血清总蛋白(TP)和白蛋白(Alb)含量,酶联免疫吸附试验(ELISA)法测定血清透明质酸(HA)和层黏连蛋白(LN)含量,光镜观察急性肝损伤和慢性肝纤维化肝组织的形态学改变。结果生姜油可显著降低皮下注射四氯化碳致大鼠慢性肝纤维化的ALT和AST水平(P<0.05,P<0.01);明显降低肝纤维化大鼠血清HA和LN含量(P<0.01);明显升高肝纤维化大鼠TP、Alb水平(P<0.01);光镜下生姜油给药组与模型组比较,可抑制慢性肝纤维化时肝假小叶的形成和胶原纤维沉积(P<0.05,P<0.01)。结论生姜油可抑制四氯化碳造成的大鼠慢性肝纤维化形成。     

软肝宁对大鼠肝纤维化的保护作用研究

目的探讨软肝宁对肝纤维化大鼠的影响,为临床适应证提供实验依据。方法将60只大鼠随机分为6组。正常对照组给予生理盐水;模型组给予20%四氯化碳花生油溶液按10 mL/kg皮下注射,首剂加倍,每5 d注射1次,首次注射后,用生理盐水按10 mL/kg灌胃,1次/天,连续6周;秋水仙碱组配成0.01 g/L;软肝宁高、中、低剂量组（0.12,0.06,0.03 g/kg）按损伤模型组同法给予CCl4造模,然后给予软肝宁给药,1次/天。给药6周后检测大鼠血清中的丙氨酸氨基转移酶（ALT）、天门冬酸氨基转移酶（AST）、超氧化物歧化酶（SOD）、丙二醛（MDA）、血清透明质酸（HA）、层粘连蛋白（LN）、Ⅲ型前胶原（PCⅢ）和羟辅氨酸（HYP）,并观察大鼠肝组织常规病理改变。结果软肝宁能改善肝纤维化大鼠的肝功能,高、中剂量可显著降低CCl4致大鼠肝损伤血清ALT,AST,MDA,HA,LN,PCⅢ水平和肝组织中过高的HYP（P〈0.05或P〈0.01）,并能升高血清中SOD含量。常规病理显示,中、高剂量软肝宁可明显减轻CCl4所致的大鼠肝细胞变性、坏死及肝组织损害程度。结论软肝宁具有延缓CCl4所致肝纤维化进程的作用。     

软肝片抗肝纤维化作用的实验研究

目的探讨软肝片对四氯化碳中毒性肝纤维化的防治作用。方法用四氯化碳皮下注射造成大鼠肝纤维化模型 ,以联苯双酯作为阳性对照 ,测定血清丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶 (AST)、玻璃酸(HA)、唾液酸及肝组织羟脯氨酸 (Hyp)、丙二醛 (MDA)、超氧化物歧化酶 (SOD)含量 ,以反映肝细胞损伤及肝纤维化程度。结果软肝片可明显降低肝纤维化大鼠血清ALT、AST、HA、唾液酸水平及肝组织Hyp和MDA水平 ,提高肝组织中SOD活力。结论软肝片具有一定的抗肝纤维化及抗脂质过氧化作用。     

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。     

高山红景天对实验性大鼠肝纤维化的抑制作用

目的：观察单方生药高山红号天对大鼠实验性肝纤维化的治疗效果，并探讨其作用机制。方法：用四氯化碳诱导大鼠肝纤维化模型，将实验动物随机分为正常对照组（A）、模型组（B）、秋水仙碱组（C）、红景天高剂量组（D）、红景天低剂量组（E）。除正常对照组外，其余4组均用四氯化碳诱发肝纤维化。各组于造模第8周末处死动物，分别用放射免疫法检测血清层粘连蛋白（LN），Ⅲ型前肢原（PCⅢ），透明质酸（HA）及Ⅳ型胶原（CⅣ）；检测ALT、AST、ALB、STP；作HE染色。结果：与模型组大鼠比较．经该中药治疗．大鼠血清中LN、PCⅢ、HA、CⅣ和ALT、AST水平明显降低（P〈0．01）；ALB水平显著升高（P〈0．01）；大鼠肝组织病理学检测改善显著。结论：单方生药高山红景天能有效地减轻肝纤维化大鼠的肝脏损伤和抑制肝纤维化的作用，其机制是通过抑制肝HSC增殖，降低ECM的分泌．促进胶原纤维降解而达到的。     

复方熊去氧胆酸口服液对大鼠肝纤维化的防治作用

目的：观察复方熊去氧胆酸口服液（C-UDCA）对四氯化碳（CCl4）致大鼠肝纤维化的防治作用。方法：采用皮下注射40%CCl4-花生油溶液制备肝纤维化模型,检测经口给予C-UDCA后对大鼠肝功能指标、肝纤维化各项生化指标及肝组织病理形态学的影响。结果：C-UDCA各剂量组能显著减轻CCl4导致的肝脂肪变性、肝细胞损伤和纤维组织增生。与UDCA相比,C-UDCA-H能显著降低血清ALT、AST、HA、PCⅢ、CⅣ、LN及肝组织Hyp含量,显著升高血清Alb、A/G、肝组织GSH含量;C-UDCA-M亦能显著降低血清HA、LN 含量。结论：C-UDCA对CCl4致大鼠肝纤维化具有一定的防治作用,且C-UDCA-H、C-UDCA-M的作用优于UDCA。     

赤芍水提物对四氯化碳致肝损伤大鼠的保护作用

目的：探讨赤芍水提取物对四氯化碳(CCl4)中毒性肝纤维化大鼠的治疗作用。方法：复制大鼠CCl4肝纤维化模型，以马洛替酯为阳性对照，采用光镜观察组织学改变， 测定血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、一氧化氮(NO)、透明质酸(HA)、层粘蛋白(LN)，肝组织羟脯氨酸(Hyp)、丙二醛(MDA)以反映肝细胞损伤及肝纤维化的程度。结果：赤芍水提物能降低实验性肝纤维化大鼠血清中升高的ALT、AST、NO、HA、LN水平和肝组织中过高的Hyp、MDA的含量。病理组织学检查亦表明，赤芍水提物明显改善实验性肝纤维化。结论：赤芍水提物对实验性肝纤维化具有治疗作用。     

乾坤宁保肝作用的实验研究

用四氯化碳（ＣＣｌ_４）诱导大鼠肝脏损伤，同时用乾坤宁灌喂以保护肝脏损伤，实验结束取动物血测定ＡＬＴ、ＡＳＴ、羟脯氨酸等生化指标，并对肝脏作组织病理学观察。实验各组的ＡＬＴ、ＡＳＴ均显著低于单用ＣＣｌ４组（Ｐ＜０．０１）；羟脯氨酸也低于单用ＣＣｌ_４组（０．０５＜Ｐ＜０．１）；组织病理观察发现，实验各组肝脏病理改变均轻于单用ＣＣｌ_４组，结果表明，乾坤宁对ＣＣｌ_４所致大鼠肝脏形态和功能损伤有明显的保护作用，对肝纤维化有一定预防作用。     

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.     

鲨鱼肝再生因子对大鼠慢性肝损伤的治疗作用

目的:探讨鲨鱼肝再生因子(sHRF)对大鼠慢性肝损伤的治疗作用。方法:CCl4致大鼠慢性肝损伤模型,给药后取血清及肝组织测定各项肝指标。结果:当用药8周时,对CCl4引起的肝损伤大鼠血清中AST、ALT活性的升高和羟脯氨酸含量的升高均有抑制作用,且0.8、1.6mg/kg剂量组的作用差异均有统计学意义。此外,sHRF能在一定程度上增加白蛋白含量,并使白蛋白/球蛋白比值有一定程度的升高。肝组织病理切片亦显示sHRF能减轻CCl4所致大鼠肝细胞脂肪变性及纤维组织增生。结论:sHRF对CCl4所致大鼠慢性肝损伤有一定的治疗作用。     

Effect of matrine hydrochloride on liver injury

Objective Searching the function that the Injection of the matrine hydrochloride prevents and cures acute chemical liver injury of mice、immunity liver injury of mice and chronic liver injury of rats.Methods Acute hepatic injury models of mice induced by Chemical poison carbon tetrachloride(CCl4),thioacetamide(TAA),D-galactosamine(D-GalN),immunity hepatic injury model of mice induced by BCG and fat polysaccharide(LPS),chronic liver injury model of rats induced by CCl4 were introduced in the experiment.The serum ALT and AST were measured in acute hepatic injury experiments.Serum ALT,AST,AKP,ALB,TP,BiL-T,creatinine,triglyceride,sialic acid,laminin,hyaluronic acid,type Ⅲ procollagen and type Ⅳ collagen,hepatic hydroxyproline(HyP)of rats in chronic liver injury animals were determined after Injection of the matrine hydrochloride.Results The Injection of the matrine hydrochloride reduced serum ALT and AST level of acute chemical liver injury of mice induced by CCl4,TAA and D-GalN.The index of the liver and the spleen of immunity liver injury of mice induced by BCG and LPS were decreased after the injection of matrine hydrochloride treatment.Compared with the model group,the injection may obviously inhibited serum ALT,AST,TP,AKP,TRI,BiL-T,creatinine,triglyceride,sialic acid,laminin,hyaluronic acid,type Ⅲ procollagen and type Ⅳ collagen activity of chronic liver injury of rats induced by CCl4,elevated ALB、A/G,reduced the liver HyP,decreased the index of the liver and the spleen.The liver visual observation,the pathology inspection and the HAI grading result showed the injection may reduce the inflammatory activity in liver tissue,restrain the liver cell damage,reduce the pseudolobuli formation.Conclusions The Injection of matrine hydrochloride had the protective function to acute chemical hepatic injury of mice induced by CCl4、TAA、D-GalN、immunity hepatic injury of mice induced by the BCG and LPS and chronic liver injury of rats induced by CCl4.     

Protective effect of salvianic acid a on acute liver injury induced by carbon tetrachloride in rats

Previous research has shown that salvianic acid A [2-(3,4-dihydroxyphenyl)-2-hydroxy-propanoic acid, SA] extracted from Salvia miltiorrhiza BGE (Danshen) markedly inhibits lipid peroxidation of mitochondrial membrane of hepatic cells in vitro. The present study was conducted to examine protective effect of SA on liver injury induced by carbon tetrachloride (CCl4) and its possible mechanism in vivo. Male Sprague-Dawley rats weighing 180-200 g were used in the experiments. Five mmol/kg CCl4 in olive oil was given to rats i.p. Spectrophotometrical method was used to measure activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as well as malondialdehyde (MDA) level in hepatic tissue and the rate of superoxide anion (O2*-) generation in hepatic submitochondrial particles. Hepatic histological structure was observed under light microscopy. CCl4 caused significant changes of activities of the enzymes, MDA level, and the rate of O2*- generation and histopathological changes of acute hepatic injury were noted. SA reversed the significant changes induced by CCl4. These results demonstrate that SA produces protective action on acute hepatic injury induced by CCl4 via an antioxidative mechanism.     

甘草酸对四氯化碳致小鼠肝纤维化及骨丢失的防治作用

目的　研究甘草酸对肝纤维化小鼠骨丢失的防治作用。方法　用体积分数为 4 0 %的CCl4花生油皮sc 5wk致小鼠肝纤维化 ,观察与肝损伤相关的各种生化指标和肝脏病理切片结果以及测定小鼠右股骨的骨Ca2 + 量和其他骨微量元素以及骨羟脯胺酸的含量。结果　单用CCl4小鼠呈现典型的慢性肝损伤后肝纤维化的改变 ,骨重量和骨钙总量及骨羟脯胺酸的含量减少 (P <0 0 5 ) ,而甘草酸治疗组有明显的护肝及对抗骨丢失作用。结论　甘草酸在所用的剂量下对肝纤维化及骨丢失有一定预防作用     

恩施富硒藤茶水提液对四氯化碳致急性肝损伤小鼠的保护作用

目的 观察恩施富硒藤茶水提液对四氯化碳（CCl4）诱导的小鼠急性肝损伤的影响。方法用腹腔注射CCl4致小鼠急性肝损伤模型,测定不同剂量的恩施富硒藤茶水提液对肝损伤血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）活性、肝中超氧化物歧化酶（SOD）活性、肝中丙二醛（MDA）含量的影响。结果恩施富硒藤茶水提液具有剂量依赖性地降低CCl4致小鼠肝损伤血清ALT、AST值升高,降低肝组织匀浆中MDA的含量,增强SOD的活性（P〈0．01或P〈0．05）。结论恩施富硒藤茶水提液对CCl4致小鼠急性肝损伤具有一定的保护作用。     

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.     

The protective effects of Hibiscus sabdariffa extract on CCl4-induced liver fibrosis in rats.

Dried flower Hibiscus sabdariffa L. (HSE) extracts, a local soft drink material and medicinal herb, were studied for their protective effects against liver fibrosis induced using carbon tetrachloride (CCl(4)) in rats. Male Wistar rats were administered CCl(4) by intraperitoneal injection for 7weeks and received a normal diet or normal diet with various HSE doses (1-5%) for 9weeks. HSE significantly reduced the liver damage including steatosis and fibrosis in a dose dependent manner. Moreover, HSE significantly decreased the elevation in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It also restored the decrease in glutathione content and inhibited the formation of lipid peroxidative products during CCl(4) treatment. In the primary culture, HSE also significantly inhibited the activation of the hepatic stellate cells. These results suggested that HSE may protect the liver against CCl(4)-induced fibrosis. This protective effect appears due to HSEs antioxidant properties.