鲨肝对CCl3所致大鼠慢性肝损伤的治疗作用

从海洋生物鲨鱼肝脏纯化获得一种活性多肽一鲨肝肽,研究了其对CCl4所致大鼠慢性肝损伤的治疗作用,结果表明,鲨肘肽对CCl4引起的肝损伤大鼠血清中AST,ALT活性的升高,羟脯氨酸含量的升高均有抑制作用,能增加白蛋白含量,使白蛋白／球蛋白比有一定的升高;肝组织病理切片观察显示,鲨肝肽能显著养活减轻CCl4所致大鼠肝细胞脂 变性及纤维组织增生,以上结果提示,鲨肝肽有减轻肝脏纤维化的作用,在迁慢性肝炎,肝硬化等肝病治疗中具有良好 的研究,应用前景。     

丹酚酸A抗四氯化碳中毒致大鼠肝损伤和肝纤维化的作用

目的：研究丹酚酸Ａ（ＳＡ－Ａ）抗肝损伤、肝纤维化作用。方法：采用ＣＣｌ４诱导大鼠肝损伤及肝纤维化，期间予ＳＡ－Ａ灌胃治疗，另设秋水仙碱（Ｃｏｌ）组、丹参组作对照，６周后进行肝组织病理学和Ｉ、Ⅲ型胶原免疫组化观察，肝组织羟脯氨酸（Ｈｙｄ）、丙二醛（ＭＤＡ）含量及血清ＡｌａＡＴ、ＡｓｐＡＴ和白蛋白含量测定。结果：ＳＡ－Ａ降低血清ＡｌａＡＴ、ＡｓｐＡＴ水平及肝组织ＭＤＡ、Ｈｙｄ含量，减轻肝纤维化程度，抑     

晶珠肝泰舒对大鼠实验性肝损伤的影响

目的研究藏药晶珠肝泰舒对实验性纤维化大鼠的影响。方法 60只Wistar大鼠随机分为正常对照组、模型组、联苯双酯滴丸对照组和晶珠肝泰舒高、中、低剂量组,采用CCl4诱导大鼠肝纤维化模型,晶珠肝泰舒高、中、低剂量组和联苯双酯滴丸组的大鼠自造模次日起灌胃给药,连续42 d,测定肝脏中羟脯氨酸、肝胶原蛋白和血清中血脂的含量。结果晶珠肝泰舒能降低肝纤维化大鼠肝脏中羟脯氨酸、肝胶原蛋白及血清中TCH、TG含量。结论晶珠肝泰舒对大鼠的实验性纤维化有显著疗效。     

肝舒胶囊对CCl4致大鼠慢性肝损伤的影响

目的 研究肝舒胶囊对大鼠慢性肝损伤的保护作用.方法 采用sc CCl4致大鼠慢性肝损伤,比色法测定血清中的ALT、AST、ALP、TP、ALB的含量,碱水解法测定肝组织中羟脯氨酸(HYP)的含量,并根据肝脏的脂变、炎症、水肿、细胞坏死、纤维组织增生观察病理组织学的形态变化.结果 肝舒胶囊对血清中生化指标有一定的降低趋势,可明显降低血清中ALP和肝组织中的HYP;可明显改善肝组织的病理学变化.结论 肝舒胶囊对慢性肝损伤有一定的保护作用.     

丹芪益肝颗粒对慢性肝损伤大鼠的肝保护作用

［摘要］目的验证丹芪益肝颗粒对四氯化碳（CCl4）所致大鼠慢性肝纤维化模型的肝保护作用及抗纤维化作用。方法模型组及各给药组首次皮下注射40%CCl4 5 mL•kg-1，以后每3 d注射1次40% CCl4 3 mL•kg-1，正常对照组给予等容积橄榄油，持续9周，给药自造模之日开始。结果CCl4所致慢性肝纤维化大鼠有明显肝损伤及慢性纤维化表现，丹芪益肝颗粒3个剂量组肝功能指标均有不同程度的改善；5，10 g•kg-1组肝组织胶原蛋白含量较模型组均明显降低；2.5 g•kg-1组血清玻璃酸（HA）较模型组显著降低；病理组织学检查结果表明其肝脏病变程度均较模型组明显减轻。结论丹芪益肝颗粒对慢性肝纤维化大鼠具有肝保护作用及抗肝纤维化作用。     

白藜芦醇对大鼠慢性肝纤维化的影响

目的:观察白藜芦醇对四氯化碳(CCl4)致大鼠慢性肝纤维化的影响.方法:Wistar大鼠皮下注射50?l4 1 mL·kg-1,每周2次,共10周.设白藜芦醇25,50,100 mg·kg-1组,每组10只大鼠,连续灌服6周.检测大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总蛋白(TP)和白蛋白(ALB)水平,测量肝组织羟脯氨酸(Hyp)和丙二醛(MDA)水平,肝组织胶原纤维染色后半定量分析和肝组织病理组织学检查.结果:高剂量组的ALT明显低于模型对照组(P<0.01).中剂量组和高剂量组肝组织Hyp和MDA水平、胶原化程度明显低于模型对照组.结论:白藜芦醇对肝纤维化可能有治疗作用.     

肝乐宁粉针剂对实验性肝损伤的保护作用

研究肝乐宁粉针剂对实验性肝损伤的保护作用。方法：采用四氯化碳致小鼠和大鼠肝脏损伤,测定生化指标及观察病理组织学改变。结果：肝乐宁粉针剂能显著降低四氯化碳引起的急性肝损伤小鼠和慢性肝损伤大鼠血清丙氨酸氨基转换酶和天门冬氨酸氨基转换酶增高;亦能明显降低大鼠血清唾液酸和肝羟脯氨酸含量,升高血清总蛋白和白蛋白水平;病理组织学检查肝乐宁粉针剂明显减轻肝细胞的变性和坏死,并抑制慢性肝损伤胶原纤维形成。结论：肝乐宁粉针剂具有肝细胞保护及抗肝纤维化作用。     

黄根片对四氯化碳致大鼠慢性肝损伤的影响

目的：探讨黄根片对大鼠慢性肝损伤的防治作用.方法：50只Wistar大鼠随机分为空白对照组、模型组、阳性对照组（联苯双酯滴丸,0.2 g·kg-1）、黄根片高、低剂量（36 g·kg-1,9 g·kg-1）组.除空白对照组外,其余各组大鼠每周2次皮下注射四氯化碳复制慢性肝损伤模型,同时每天灌胃给药1次,连续12周,观察黄根片对慢性肝损伤大鼠血液生化指标以及肝组织病理变化的影响.结果：与空白对照组比较,模型组大鼠造模后12周体质量、残留肝组织百分率显著降低,肝脏系数、肝组织Hyp含量、血清ALT、AST含量显著升高,血清TP、Alb含量显著降低（P＜0.05或0.01）.与模型组比较,黄根片高、低剂量组灌胃给药12周能够显著提高大鼠血清TP含量和残留肝组织百分率（P＜0.05）.结论：黄根片对四氯化碳致大鼠慢性肝损伤模型有一定的保护作用.     

珠子肝泰对实验性慢性肝损伤的影响

目的观察珠子肝泰合剂对慢性肝损伤的作用。方法采用适量四氯化碳(CCl4)多次注射造成慢性肝损伤模型,给予同剂量的珠子肝泰合剂,测定血清转氨酶(ALT、AST)、胆碱酯酶(CHE),肝组织匀浆ALT与CHE、谷胱苷肽(GSH)、丙二醛(MDA)、碱性磷酸酶(ALP),HE染色观察肝组织形态学。结果珠子肝泰合剂能有效地降低CCl4所致慢性肝损伤大鼠血清与匀浆ALT,升高血清CHE,降低GSH与MDA,HE显示受损的肝细胞有用药后较好的恢复作用。结论珠子肝泰合剂对皮下注射四氯化碳致大鼠慢性肝损伤具有显著的治疗作用,主要表现在能明显降低肝脏重量指数,降低ALT、AST,能升高血清白蛋白(ALB),纠正白球蛋白比(A/G),显著减轻慢性肝损伤大鼠病理损伤,提示该制剂对慢性肝损伤有保护作用。降低肝组织胶原纤维含量(胶原总数目、胶原总面积),抑制胶原纤维生成,减轻肝硬化病变。     

CCl4诱导大鼠肝纤维化模型的建立

目的：构建肝纤维化大鼠动物模型。方法：取雄性Sprague—Dawley（SD）大鼠80只,通过腹腔注射以橄榄油稀释10N的四氟化碳．1mL／kg．每周1次．共8周．建立大鼠肝纤维化动物模型。造模结束时处死动物。酶联免疫吸附法检测血清ALT、AST水平．HE染色及免疫荧光法观察大鼠肝组织病理学变化和胶原沉积。分别观察在造模第5、6、7、8周时各项指标的变化。结果：建模第5周即可见肝功异常．血清AL丁和AST明显升高（P〈0．05）。第6周肝脏假小叶形成。大鼠肝脏有明显的纤维化病灶。于第7周始最为典型。大鼠HE染色中可见肝组织病变区域多,面积大,正常肝小叶结构破坏．肝细胞索排列紊乱．胶原纤维明显增生。呈较宽的务索状分隔肝小叶,弥漫分布,形成假小叶。建模成功率高达80．0％。结论：CCL诱导可成功建立大鼠肝纤维化模型。     

银杏内酯对CCl4诱导的小鼠肝损伤的作用研究

目的 探讨银杏内酯对CCl4诱导的小鼠肝损伤的保护作用及其机制.方法 随机将50只SD小鼠分为5组,分别为空白对照组、模型组、银杏内酯低剂量组、银杏内酯中剂量组和银杏内酯高剂量组.采用CC14腹腔注射和灌胃制作小鼠肝损伤模型.通过观察肝脏的解剖学形态,检测血丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平来评估银杏内酯对小鼠肝脏的保护作用.Real time-PCR检测孕烷X受体（PXR）、CYP3A 11、CYP3A13和RXRα的表达.结果 与空白对照组相比,模型组小鼠肝脏表面粗糙、轮廓萎缩;血清ALT和AST水平明显升高.与模型组相比,银杏内酯组小鼠肝脏表面光滑、轮廓清晰;血清ALT和AST水平明显降低,肝脏PXR、RXRα、CYP3A13和CYP3A11表达水平明显升高.结论 银杏内酯对CCl4诱导的小鼠肝损伤有一定的保护和修复作用,其保护效果呈明显剂量依赖性.PXR、RXRα、CYP3A13、CYP3A 11基因表达的上调可能在小鼠肝损伤保护中起重要作用.     

藤茶双氢杨梅树皮素对实验性慢性肝损伤的保护作用

目的：探讨从藤茶提取的双氢杨梅树皮素（APS）对慢性肝损伤的保护作用。方法：采用四氯化碳（CCl4）建立小鼠慢性肝损模型，并给予APS观察其对实验鼠血清丙氨酸氨基转移酶（ALT），天门冬氨酸氨基转移酶（AST）活性，总蛋白（TP），白蛋白（ALB），透明质酸（HA）含量和肝组织羟脯氨酸（HyP）含量的影响及肝组织病理改变的影响。结果：APS明显降低血清ALT，AST活性，血清HA含量和肝组织HyP含量，明显增高血清TP和ALB含量，同时可减轻实验鼠肝组织病理改变的程度。结论：APS对CCL4所致实验性慢性肝损伤具有明显的保护作用。     

肝脏损害对染镉大鼠镉分布的影响

大鼠腹腔内注射ＣｄＣｌ２０．５ｍｇＣｄ＾２＋／Ｋｇ体重，每周三次，共１０周。注射ＣｄＣｌ２第４周末，其中一组动物灌胃ＣＣｌ４９００ｍｇ／ｋｇ体重。结果表明ＣｄＣｌ２＋ＣＣｌ４组动物肝脏损害后肝镉浓度明显低于单纯ＣｄＣｌ２组，同时伴随血镉，肾镉水平显著升高。肝、肾中金属硫蛋白浓度也与相应组织中隔浓度呈类似的变化形式。ＣｄＣｌ２＋ＣＣｌ４组动物尿镉和尿金属硫蛋白浓度均明显高于ＣｄＣｌ２组。这些实验     

抑肽酶对实验性慢性肝损伤超微结构改变的影响

目的探讨抑肽酶对实验性慢性肝损伤肝组织超微结构改变的影响。方法建立大鼠急性四氯化碳(CCl4)肝损伤模型,分为正常对照组,模型组,抑肽酶小、中、大剂量组及甘利欣注射液组。各组大鼠取肝组织做超薄切片,醋酸双氧铀-柠檬酸铅双重染色,透射电镜下观察其肝组织超微结构的改变。结果模型组肝细胞呈肿胀状,细胞界限不清,胆小管两端紧密连接消失;腔面微绒毛减少。肝细胞核呈圆形固缩状;核内异染色质凝聚、趋边;核基质空化。抑肽酶小剂量组肝细胞体积大小不一,个别细胞呈固缩状。胆小管轻度扩张;小管两端连接结构清晰;腔面微绒毛减少,并可见髓样小体。抑肽酶中剂量组肝细胞体积稍大;胆小管两端紧密连接结构清楚;腔面微绒毛较多。核呈圆形,核仁明显,可见少量块状的异染色质。抑肽酶大剂量组肝细胞结构接近空白对照组,细胞体积较大,细胞界限清楚;胆小管结构正常。肝细胞核较大,呈圆形,核膜清晰;核内常染色质多,可见少量小块状的异染色质;核仁多个。促肝细胞生长素组肝组织超微结构改变与抑肽酶中剂量组相似。结论抑肽酶对实验性大鼠慢性肝损伤的肝组织超微结构具有明显的保护作用。随着抑肽酶剂量的增大,肝组织超微结构改变明显改善。     

清肝抑脂汤对慢性肝损伤保护作用的研究

目的：探索清肝抑脂汤（QYT）抗慢性肝损伤的保护作用的影响。方法将小鼠随机分为空白对照组,模型组,阳性药物组,清肝抑脂汤高剂量组,清肝抑脂汤低剂量组。首先建立慢性肝损伤模型,除空白对照组外,其余各组小鼠分别腹腔注射10%CCl4溶液,0.1ml/10g,每周2次,共6周。在建模的同时,各组小鼠分别给予相应的药物治疗。末次给药后次日摘眼球取血,分离血清,检测小鼠血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）酶的活性;同时取肝脏,常规病理切片,观察肝组织病理学变化。结果肝组织病理切片显示清肝抑脂汤能改善肝损伤程度;清肝抑脂汤能显著降低小鼠血清ALT（P<0.05,P<0.01）和AST（P<0.05,P<0.01）酶活性。结论清肝抑脂汤能显著降低受试小鼠血清ALT,AST及ALP酶活性,清肝抑脂汤对CCl4所致小鼠慢性肝损伤具有明显的保护作用。     

Ketoprofen glucuronidation and bile excretion in carbon tetrachloride and alpha-naphthylisothiocyanate induced hepatic injury rats

A pharmacokinetic study was carried out in rats to investigate the effects of experimental hepatic injury on the liver glucuronidation and bile excretion of ketoprofen (KP) and its glucuronides (KPGs). In vivo, KP (20 mg/kg b.w.) was intravenously administered to carbon tetrachloride (CCl₄) or alpha-naphthylisothiocyanate (ANIT) induced hepatic injury male rats. Concentrations of KP and its glucuronides (S-KPG and R-KPG) in plasma and bile were determined by RP-HPLC. It was observed that there was significant difference in the accumulative bile excretion of KPGs between the CCl₄ intoxicated rats and the normal rats (54 ± 18.3% versus 90 ± 6.9%), while it was extremely inhibited in ANIT intoxicated rats (2.0 ± 3.1% versus 90 ± 6.9%). As the result of reduction of KPGs excreted in bile, the area under the curve (AUC_(0–∞)) of KP and KPGs were higher in blood in CCl₄ and ANIT hepatic injury rats than those of the normal rats. Specifically, ANIT caused approximately 10-fold elevation of AUC_(0–∞) of plasma S-KPG. In microsomal incubations experiment, the glucuronyltransferase activity was impaired in CCl₄ and ANIT intoxicated rats. It suggested that the glucuronyltransferase activity was impaired in CCl₄ and ANIT intoxicated rats, while the bile excretion function was suppressed extremely in ANIT intoxicated rats.     

Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis

Effective and well-tolerated anti-fibrotic drugs are currently lacking. Therefore, this study was carried out to investigate the potential anti-fibrotic effects of imatinib, nilotinib and silymarin on established hepatic fibrosis in the carbon tetrachloride (CCl₄) rat model. Male Wistar rats received intraperitoneal injections of CCl₄ twice weekly for 8 weeks, as well as daily intraperitoneal treatments of imatinib (10 and 20 mg/kg), nilotinib (10 and 20 mg/kg) and silymarin (100 mg/kg) during the last 4 weeks of CCl₄-intoxication. At the end of the study, hepatic damage was evaluated by analysis of liver function tests and hepatic oxidative stress parameters. Hepatic fibrosis was evaluated by histopathology and morphometry, as well as collagen and 4-hydroxyproline contents. Nilotinib (20 mg/kg) was the most effective treatment to counteract CCl₄-induced hepatic injury as indicated by liver function tests and histopathology. Nilotinib (10 mg/kg), nilotinib (20 mg/kg) and silymarin (100 mg/kg) treatments reduced the mean score of hepatic fibrosis by 31%, 68% and 47%, respectively, and hepatic collagen content by 47%, 49% and 18%, respectively in CCl₄-treated rats. Hepatic morphometric evaluation and 4-hydroxyproline content revealed that CCl₄-induced fibrosis was ameliorated significantly by nilotinib (20 mg/kg) and imatinib (20 mg/kg). Unlike nilotinib, imatinib (20 mg/kg) showed some sort of hepatic injury evidenced by elevation of serum aminotransferases and total bilirubin levels, and hepatic total nitrate/nitrite content, as well as characteristic anisonucleosis visualized with the hematoxylin-eosin staining. In conclusion, this study provides the evidence that nilotinib exerts anti-fibrotic activity and suggests that it may be valuable in the treatment of hepatic fibrosis in humans.     

柴胡对大鼠实验性肝纤维化的预防作用

目的研究中药柴胡对肝纤维化的预防作用。方法采用四氯化碳(CCL4)诱发大鼠肝损伤,辅以高脂、低蛋白饲料和一定浓度乙醇饮料,复制肝纤维化模型,柴胡预防给药,观察其对大鼠血清及肝组织生化指标的影响。结果柴胡预防给药可显著降低四氯化碳所致慢性肝损伤大鼠血清ALT、AST和肝组织MDA、HyP,提高肝组织SOD活性。病理组织学观察显示,柴胡可使肝组织变性、坏死程度减轻。结论柴胡能预防四氯化碳致大鼠肝纤维化的发生与发展。     

岩柏草总黄酮抗大鼠肝纤维化的实验研究

目的:探讨岩柏草总黄酮对实验性肝纤维化大鼠的保护作用。方法:采用50%CCl4皮下注射8周,在造模同时分别灌胃15、30、60 mg/kg剂量岩柏草总黄酮混悬液,并以水飞蓟宾为实验对照。8周后处死大鼠,对大鼠肝脏纤维化评分,并检测血清和肝组织各指标。结果:CCl4造模结束后,大鼠肝组织病理结果显示其肝纤维化处于III-IV期;与模型组比较,岩柏草总黄酮能显著降低大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)和肝组织中丙二醛(MDA)水平,明显升高肝组织中超氧化物歧化酶(SOD)水平,显著改善大鼠肝纤维化的病理形态。结论:岩柏草总黄酮对CCl4诱导的大鼠肝纤维化有较好的保护作用。     

PEGylated lactoferrin enhanced its hepatoprotective effects on acute liver injury induced by carbon tetrachloride in rats

Polyethylene glycol (PEG) is attached to proteins in order to increase their half-life in circulation and reduce their immunogenicity in vivo. The present study was conducted to examine whether two different sizes of PEGylated bovine lactoferrin (40k-PEG-bLf and 20k-PEG-bLf) would enhance the protective effect of native bLf on liver injury induced by carbon tetrachloride (CCl₄) in rats. Silymarin, a known hepatoprotective drug was used as a positive control. Compared to native bLf, the treatment of PEGylated bLf more markedly prevented the elevation of serum levels of hepatic enzyme markers and inhibited fatty degeneration and the hepatic necrosis induced by CCl₄. 40k-PEG-bLf showed a more significant suppressive effect on CCl₄-induced hepatic injury than 20k-PEG-bLf. The treatment with PEGylated bLf elevated serum SOD activity reduced by CCl₄ more significantly than native bLf. 40k-PEG-bLf enhanced serum SOD activity more significantly than 20k-PEG-bLf. Immunohistochemical study showed that the PEGylation of bLf enhanced its intracellular transportation to hepatocytes. The increases in intracellular transportation of the PEGylated bLf in order were: 40k-PEG-bLf > 20k-PEG-bLf > native bLf. These findings suggested that the mechanism of the enhancement of hepatoprotective effect by PEGylated bLf was associated with an increase in the intracellular transportation of PEGylated bLf in hepatocytes.