复肝丸对小鼠和大鼠肝纤维化模型的影响

目的:观察复肝丸对四氯化碳诱导的小鼠肝纤维化和二甲基亚硝胺诱导的大鼠肝纤维化的防治作用。方法:小鼠随机分为正常组、模型组、复肝丸组和培哚普利,除正常组外,其余组腹腔注射四氯化碳复制肝纤维化模型;自造模之日起各组灌胃4周。大鼠随机分为正常组、模型组、复肝丸组和培哚普利,除正常组外,其余各组腹腔注射二甲基亚硝胺4周复制肝纤维化模型;造模结束后各组灌胃4周。称重测量肝体比、脾体比,比色法测定血清谷丙转氨酶和谷草转氨酶活性,溴甲酚绿法测定血清白蛋白水平,碱消化法测定肝组织羟脯氨酸含量,HE染色观察肝组织炎性变化、天狼猩红胶原染色观察肝组织病理性胶原沉积变化。结果:与模型组相比,复肝丸10g生药/kg小鼠体重预防用药或6g/kg大鼠体重治疗用药均能降低大鼠和小鼠血清谷丙转氨酶和谷草转氨酶活性,减轻肝脏炎性病理,降低肝组织羟脯氨酸水平,改善肝组织病理性胶原沉积增生。结论:复肝丸对大鼠和小鼠肝纤维化具有防治作用。     

Effects and mechanisms of crude astragalosides fraction on liver fibrosis in rats

Astragalosides is the major active constituent of Radix Astragali. The present study was carried out to investigate the effect of crude astragalosides fraction (CAF) on rats liver fibrosis and its possible mechanisms. Hepatic fibrosis was induced by subcutaneous injection with 50% CCl(4) in Sprague-Dawley rats. The amount of CCl(4) administered was 1 mg kg(-1). The alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in plasma and hydroxyproline (Hyp), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) contents in liver tissue were assayed by spectrophotometry. The 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) were determined with ELISA. Liver samples collected after 8 weeks of CCl(4) treatment were stained with hematoxylin-eosin (HE) and massion, and scored. Intragastric administration of CAF (10, 20 and 40 mg kg(-1)) significantly decreased indices of liver and spleen, the serum transaminase activities, HA and PC III levels, and Hyp and MDA contents in liver tissue in rats of hepatic fibrosis. Decreased SOD and GSH-px levels were reversed after administration of CAF. Histopathological scores showed CAF had inhibitory effect on the progression of hepatic fibrosis. In the in vitro experiments, CAF significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of KCs. The results showed CAF significantly inhibited the progression of hepatic fibrosis induced by CCl(4), and the inhibitory effect of CAF on hepatic fibrosis might be associated with its ability to scavenge free radical and inhibit the production of TNF-alpha and TGF-beta1 from activated KCs.     

沙棘籽油对大鼠实验性肝纤维化的保护作用

目的 :观察沙棘籽油对大鼠肝纤维化的影响。方法 :用CCl4反复给予诱发大鼠产生肝纤维化 ,观察沙棘籽油的效果。结果 :CCl4组大鼠血清ALT、AST活力和肝脏羟脯氨酸含量明显增高 ,体重减轻。沙棘籽油 0 7和 0 3 5 g/kg均能抑制CCl4所致肝损伤大鼠血清ALT活力的升高 ,还可使肝脏羟脯氨酸含量下降 ,但对AST活力、总蛋白、白蛋白和球蛋白含量无明显影响。给药组大鼠肝脏脂肪变性、肝细胞坏死和纤维化均有所减轻。结论 :沙棘籽油对CCl4所致大鼠肝纤维化有一定保护作用。     

藏药郎庆阿塔治疗肝纤维化的实验研究

目的:研究藏药郎庆阿塔对复合因素所致大鼠肝纤维化的治疗作用.方法:清洁级Wistar大鼠90只采用复合因素(高脂低蛋白饲料喂养、含乙醇饮用水加皮下注射四氯化碳)制备大鼠肝纤维化模型,造模6周末随机处死12其造模大鼠,通过肝组织病理检查及血清肝功能指标来检查肝纤维化模型成功率.将模型大鼠随机分为模型对照组、阳性药复方鳖甲软肝片组(0.55 g·kg-1)、郎庆阿塔颗粒给药高、中、低剂量组(生药11.4,5.7,2.85 g·kg-1),另设正常对照组.各组大鼠于分组后即日(第7周)开始ig给药,每日1次,连续ig给药7周.治疗结束后,检测血清中生化指标和肝纤维化指标,并取肝脏组织,测定肝脏组织中羟脯氧酸含量、超氧化物歧化酶(SOD)活力及丙二醛(MDA)水平,另取肝脏组织标本进行病理组织学检查.结果:郎庆阿塔能明显降低肝纤维化大鼠增高的肝脏系数和肝组织中羟脯氨酸含量(P ＜0.05～p＜0.01),显著降低肝纤维化大鼠血清中异常升高的天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)、总胆红素(T-BIL)、透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原氨端肽( PⅢ NP)及Ⅳ型胶原(CⅣ)(P＜0.05～P＜0.01),升高白蛋白(ALB)和A/G,比值,能明显升高肝组织中SOD活力(P＜0.05～P＜0.01)、降低异常升高的MDA水平(P ＜0.05～P＜0.01),病理组织学检查结果表明郎庆阿塔高、中剂量对肝纤维化大鼠肝纤维组织增生、肝组织炎症活动度均有显著的改善作用(P ＜0.05～P＜0.01),并能显著降低肝组织中胶原纤维面积(P＜0.05～P＜0.01).结论:藏药郎庆阿塔具有明显的治疗肝纤维化作用.     

Further studies on the hepatoprotective effects of Anoectochilus formosanus

The purpose of this study was to investigate the hepatoprotective effects of Anoectochilus formosanus effective fraction (AFEF) on chronic liver damage induced by carbon tetrachloride (CCl4) in mice. CCl4 (5%; 0.1 mL/10 g body weight) was given twice a week for 9 weeks, and mice received AFEF throughout the whole experimental period. Plasma GPT, hepatic levels of hydroxyproline and malondialdehyde were significantly lower in mice treated with AFEF compared with those treated with CCl4 only. Liver pathology in the AFEF-treated mice was also improved. RT-PCR analysis showed that AFEF treatment increased the expression of methionine adenosyltransferase 1A and decreased the expression of collagen(alpha1)(I) and transforming growth factor-beta1. These results clearly demonstrated that AFEF reduced the hepatic damage induced by CCl4 in mice.     

肝纤康对大鼠肝纤维化的抑制作用及其机制研究

目的观察肝纤康对CCl4诱导的大鼠肝纤维化的影响并探讨其可能机制。方法用CCl4复制大鼠肝纤维化模型,同时予以肝纤康灌胃治疗,测定血清ALT、MDA、HA、LM及肝组织GSH、Hyp含量,并观察肝组织病理变化。结果模型组血清ALT、MDA、HA、LM及肝组织Hyp含量显著升高,肝组织GSH含量显著降低,肝纤维化病变明显;肝纤康治疗组血清ALT、MDA、HA、LM及肝组织Hyp含量明显降低,肝组织GSH含量明显升高,肝纤维化病变明显减轻。结论肝纤康对大鼠肝纤维化具有明显抑制作用,其机制可能与减轻肝细胞脂质过氧化损伤,减少细胞外基质在肝组织沉积有关。     

Effect of a urinary preparation on liver injury by short-term carbon tetrachloride treatment in rats.

The hepatoprotective effect of a preparation of human urine (PHU) was assessed against short-term carbon tetrachloride (CCl4) treatment in rats. Significant prevention of liver injury by PHU was found after CCl4 treatment, judging by the changes of serum biochemical parameters, and hepatic protein and triglyceride contents. The increased liver lipid peroxidation, and decreased liver vitamin C concentrations observed after CCl4 treatment were significantly prevented by PHU administration. The increase in liver glutathione (GSH) contents observed after CCl4 treatment was further increased by PHU treatment. Liver catalase activity decreased after CCl4 treatment, while liver superoxide dismutase and GSH-peroxidase activities did not change. PHU administration further inhibited the decrease in liver catalase activity after CCl4 treatment. These results indicate that PHU administration can prevent liver injury induced by CCl4 in rats by inhibiting enhanced lipid peroxidation and by improving disrupted active oxygen metabolism in the injured liver.     

Preventive and curative effect of Lygodium flexuosum (L.) Sw. on carbon tetrachloride induced hepatic fibrosis in rats

The preventive and curative effect of Lygodium flexuosum on experimentally induced hepatic fibrosis by carbon tetrachloride (CCl(4)) was evaluated in rats. Hepatic fibrosis was induced in male Wistar rats by CCl(4) administration (150 microL/100g rat weight, oral) twice a week for 10 weeks. In preventive treatment daily doses of Lygodium flexuosum n-hexane extract (200 mg/kg, p.o) was administered for 10 weeks. In curative treatment Lygodium flexuosum extract (200 mg/kg, p.o) was given for 2 weeks after the establishment of fibrosis for 10 weeks. Treatment with CCl(4) caused a significant decrease in body and liver weight. Lygodium flexuosum n-hexane extract prevented or reversed the decline in body and liver weight. Treatment with the extract prevented or restored the elevation of serum AST, ALT and LDH levels. Lygodium flexuosum treatment remarkably prevented or reversed an increase in liver hydroxyproline content in chronically treated rats. Histopathological changes of hepatic lesions induced by CCl(4) were significantly (p < or = 0.05) improved by treatment with Lygodium flexuosum. These results support that Lygodium flexuosum exerts effective protection in carbon tetrachloride induced hepatic fibrosis in rats.     

丹参滴丸对CCl4诱导的大鼠肝纤维化的影响及其作用机制

目的 观察丹参滴丸对CCl4致大鼠肝纤维化的保护作用,并探讨其作用机制.方法 除对照组外,其余各组大鼠用CCl4复合因素法诱导肝纤维化大鼠模型,丹参滴丸各组同时ig给予丹参滴丸700、350、175 mg/kg,阳性对照组给予扶正化瘀胶囊1 500 mg/kg,每天给药1次,连续给药7周,正常大鼠给予蒸馏水作为对照组.测定各组大鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)的活性及总蛋白(TP)、白蛋白(ALB)、Ⅳ型胶原的水平;测定肝组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)和羟脯氨酸(Hyp)的量;HE和Masson染色观察肝组织病理形态学改变;免疫组化法检测α-平滑肌肌动蛋白(α-SMA)的表达.结果 丹参滴丸能明显抑制肝纤维化大鼠血清中ALT、AST、NAG活性的升高,降低Ⅳ型胶原的量,增加TP和ALB的量;降低肝组织中Hyp和MDA的量,提高SOD的活性,抑制胶原纤维的增加,亦能降低α-SMA的表达.结论 丹参滴丸有明显的抗肝纤维化作用,其作用机制与其抗脂质过氧化、抑制胶原纤维的增加及降低α-SMA的表达等密切相关.     

湖北海棠叶总黄酮抗CCl4所致大鼠肝纤维化作用研究

目的:研究湖北海棠叶总黄酮对四氯化碳(CCl4)所诱导的大鼠肝纤维化的影响,并探讨其可能的作用机制。方法:腹腔注射2ml/kg CCl4橄榄油溶液制备大鼠肝纤维化模型。首次注射后分别灌胃给药湖北海棠叶总黄酮120mg/kg和60mg/kg,每天一次,共8周。测定血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、透明质酸、羟脯氨酸、β1-转化生长因子以及肝组织中总抗氧化能力、丙二醛含量和总超氧化物歧化酶的活性;用免疫组化方法定量肝组织中α-平滑肌肌动蛋白的表达。结果:与模型组比较,湖北海棠叶总黄酮能够调低血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、透明质酸、羟脯氨酸、β1-转化生长因子含量,降低肝组织丙二醛含量,增加肝组织中总抗氧化能力和总超氧化物歧化酶活性,降低α-平滑肌肌动蛋白的表达;病理学切片显示湖北海棠叶总黄酮能明显减轻CCl4引起的大鼠肝损伤及纤维化程度。结论:湖北海棠叶总黄酮在实验的120mg/kg和60mg/kg两个剂量组对CCl4致大鼠肝纤维化都有防治作用,作用机制可能与其抗氧化作用有关,湖北海棠叶总黄酮能能增强组织抗氧化能力,降低CCl4引起的脂类过氧化,保护细胞膜免受损伤,抑制β1-转化生长因子等具有加重肝纤维化程度的生物因子的表达,减轻肝纤维化程度。     

Therapeutic effect of gypenoside on chronic liver injury and fibrosis induced by CCl4 in rats

Gypenoside is a saponins extract derived from the Gynostemma pentaphyllum. The purpose of this study was to evaluate the hepatoprotective and antifibrotic potential of Gypenoside on chronic liver injury induced by CCl4 for 8 wks. The results indicated that the increase of SGOT, SGPT activities in CCl4 liver injury were significantly reduced by treatment with Gypenoside. It also elevated the A/G ratio. For the study of anti-fibrotic potential, Gypenoside reduced the collagen content by 33%. These phenomena were confirmed by pathologic observation; thinner bands of liver collagen were found. The results suggest that Gypenoside has hepatoprotective and anti-fibrotic activities.     

Prevention of Cistanche salsa Extract on Hepatic Fibrosis Induced by Carbon Tetrachloride in Rats

Objective To explore the antifibrotic effect of echinacoside on carbon tetrachloride(CCl4)-induced hepatic fibrosis in rats.Methods Male Wistar rats were randomly divided into normal control(n=8),model(n=14),and echinacoside treatment(n=14)groups.The hepatic fibrosis model was induced by CCl4compositor.The rats were ig administered with echinacoside at a daily dose of 50 mg/kg.The anti-oxidant status,liver function parameters,and hepatic hydroxyproline content were detected by chromatometry.The serum levels of hyaluronic acid(HA),type IV collagen(CIV),type III precollagen(PIIIP),and laminin(LN)were assayed with radioimmunoassay.The hpatic injury was detected by haematoxylin-eosine staining.The deposition of collagen was observed with Masson staining.Results Echinacoside increased the superoxide dismutase activity and reduced the levels of malondialdehyde,aspartate aminotransferase,alanine aminotransferase,HA,CIV,PIIIP,and LN in serum.Echinacoside could also reduce the hydroxyproline content in liver,alleviate hepatic injury,and inhibit collagen deposition.Conclusion Echinacoside possesses antihepatic fibrosis effect.     

扶正化瘀319方对二甲基亚硝胺所致大鼠肝纤维化及其白蛋白基因表达的影响

目的:观察扶正化瘀319方(简称319方)对大鼠肝纤维化及其白蛋白基因(Alb mRNA)表达的影响。方法:采用二甲基亚硝胺腹腔注射诱发的大鼠肝纤维化模型,分模型组、319方组、秋水仙碱组,分别治疗3周。进行血清丙氨酸氨基转移酶(ALT)、血清门冬氨酸氨基转移酶(AST)活性和血清白蛋白(Alb)含量、肝组织蛋白、羟脯氨酸(Hyp)含量的检测及肝组织病理学观察、Alb 表达分析。结果:较之模型组,319方组肝组织蛋白含量增高.Hyp 含量显著降低,肝纤维化程度改善明显,其结果与秋水仙碱趋势一致。此外该方可显著提高肝脏 Alb mRNA 的表达。结论:319方有显著促进胶原降解和改善肝细胞功能的作用。     

Protective effects of total flavonoids of Bidens pilosa L. (TFB) on animal liver injury and liver fibrosis

The hepatoprotective effects of total flavonoids of Bidens pilosa L. (TFB), a traditional Chinese medicine were evaluated in carbon tetrachloride (CCl(4))-induced liver injury in mice and rats. Total flavonoids of Bidens pilosa L. (25, 50 and 100mg/kg) were administered via gavage daily for 10 days to CCl(4)-treated mice as well as TFB (30, 60 and 90mg/kg) administered for 6 weeks to CCl(4)-treated rats. Liver index (liver weight/body weight), serum levels of transaminases (alanine aminotransferase, ALT and aspartate aminotransferase, AST), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were evaluated following the 10 days treatment in mice. In addition histopathologic changes and nuclear factor-kappaB (NF-kappaB) expression of the liver were detected with hematoxylin-eosin (HE) and immunohistochemistry methods, respectively. The results showed that TFB (50 and 100mg/kg) effectively reduced the CCl(4)-induced elevated liver index, serum ALT, AST levels, hepatic MDA content, and restored hepatic SOD, GSH-Px activities in acute liver injury mice. TFB (60 and 90mg/kg) treatment significantly inhibited NF-kappaB activation in liver fibrosis of rats. The histopathological analysis suggested that TFB reduced the degree of liver injury in mice and severity of liver fibrosis in rats. These results suggested that TFB had a protective and therapeutic effect on animal liver injury, which might be associated with its antioxidant properties and inhibition of NF-kappaB activation.     

The hepatoprotective activity of kinsenoside from Anoectochilus formosanus

Carbon tetrachloride (CCl(4)) causes chronic hepatitis, featuring an increase in hepatic hydroxyproline, spleen weight and serum GPT levels and a decrease in plasma albumin levels. Crude extracts of fresh whole plants of Anoectochilus formosanus showed inhibition of chronic hepatitis induced by CCl(4) in mice. Bioactivity-guided fractionation and spectroscopic analysis revealed that kinsenoside was the most active compound. In an in vitro study, the LD(50) values for H(2)O(2)-induced cytotoxicity in BALB/c normal liver cells were significantly higher after kinsenoside pretreatment than after vehicle alone, further confirming that kinsenoside shows significant antihepatotoxic activity.     

大黄素对大鼠肝纤维化形成的影响

目的；研究大黄素对肝纤维化的影响。方法：采用４０％的四氯化碳（ＣＣｌ４）给予大鼠皮下注射诱导肝纤维化，并以小，中和大剂量大黄素（２０，４０和８０ｍｇ／ｋｇ体重）干预，测定血清透明质酸，层粘连蛋白及肝组织羟脯氨酸，并通过光镜和电镜观察肝组织病理变化。结果：大黄素组较模型组；（１）血清透明质酸及层粘连蛋白显著降低；（２）肝组织胶原蛋白含量明显减少；（３）肝组织纤维化程度明显改善；（４）肝细胞损伤减轻。     

疏肝理脾片抗大鼠免疫性肝纤维化研究

用牛血清白蛋白（ＢＳＡ）造成大鼠免疫损伤性肝纤维化模型，观察疏肝理脾片对肝纤维组织增生程度、肝羟脯氨酸（Ｈｙｐ）含量和血清透明质酸（ＨＡ）及肝功能的影响。结果表明疏肝理脾片能明显降低肝Ｈｙｐ含量，减轻肝纤维组织增生程度，并较好地提高血清白蛋白水平     

青蒿琥酯抗牛血清白蛋白免疫性大鼠肝纤维化作用的研究

目的:研究青蒿琥酯抗实验性肝纤维化的作用。方法:采用牛血清白蛋白免疫性肝纤维化大鼠模型,观察肝组织病理变化,检测肝组织中羟脯氨酸的含量及动物血清肝功能指标和血清MDA水平。结果:青蒿琥酯组能减轻假小叶形成和肝组织羟脯氨酸含量升高,并能使GPT下降。结论:青蒿琥酯具有抗肝纤维化的作用。