排钱草对大鼠实验性肝纤维化的影响

目的:观察排钱草水、醇提取物对肝纤维化的影响。方法:在给大鼠皮下注射CCl_4进行肝纤维化模型制作的同时给予排钱草水、醇提取物(相当于每日原生药5g/ke、3g/kg),给药6周后检测大鼠肝组织羟脯氨酸(Hyp)及血清中谷丙转氨酶(ALT)和碱性磷酸酶(ALP)活性,血清蛋白电泳测定γ-球蛋白,并观察肝脏的组织病理改变,与联苯双酯进行药效对照。结果:排钱草水、醇提取物的高、低剂量组和联苯双酯组均能显著降低肝脏Hyp含量及血清ALT、ALP的活性,降低γ-球蛋白以维持白/球(A/G)比值,对大鼠肝细胞坏死和胶原纤维增生亦有显著减轻作用。结论:排钱草水、醇提取物能减轻CCl_4致大鼠的肝脏损害,有利于减轻肝纤维化。     

排钱草总生物碱对实验性肝纤维化动物相关指标的作用

目的 观察排钱草总生物碱对实验性肝纤维化的作用效果及其作用机制。方法 采用四氯化碳（CC14）诱导肝纤维化模型,分别按阻断肝纤维化实验研究方法和治疗肝纤维化实验研究方法,从而清相关指标、肝脏羟脯氨酸含量和病理组织学等观察排钱草总生物碱的疗效,以秋水仙碱作为阳性对照药。结果 排钱草总生物碱能显著降低肝纤维化大鼠血清ALT、HA、γ-球蛋白及肝组织羟脯氨酸含量。肝脏病理组织学检查亦显示良好的作用效果。结论 排钱草总生物碱具有较好的抗肝纤维化作用。     

养肝软坚方抗大鼠肝纤维化的实验研究

目的：探讨中药复方养肝软坚方对四氯化碳（CCl4）诱导的实验大鼠肝纤维化的治疗作用。方法：60只雄性SD大鼠随机分为：正常对照组、模型组及治疗组,除正常对照组外所有大鼠均给予皮下注射40%CCl4（每3天1次,共11周）。造模3周后治疗组大鼠给予养肝软坚方10ml.kg-1.d-1,正常对照组及模型组大鼠给予等量生理盐水,1次/d,共8周。实验结束时检测大鼠肝功能、血清透明质酸（HA）、层黏连蛋白（LN）、Ⅲ型前胶原（PCⅢ）和肝脏羟脯氨酸（Hyp）,采用光镜观察肝脏病理组织学改变。结果：养肝软坚方能改善肝纤维化大鼠的肝功能,可显著降低血清HA、LN、PCⅢ水平和肝组织中过高的Hyp,病理组织学观察表明其能显著改善肝纤维化程度。结论：养肝软坚方对CCl4诱导的大鼠具有较好的抗肝纤维化作用。     

银杏制剂对大鼠肝纤维化的作用

[目的]研究银杏制剂的抗大鼠肝纤维化作用及对血小板反应蛋白1(TSP-1)的影响。[方法]雄性大鼠70只,随机分为正常组,模型组,自然恢复组,治疗组。除正常组外,其余各组用四氯化碳(CCl4)为主的复合因素诱导肝纤维化模型,8周造模结束后治疗组予银杏制剂灌胃治疗8周,取各组大鼠肝组织苏木精-伊红、Masson染色作病理观察及纤维化分级,测定肝脏指数,血清透明质酸(HA),肝组织羟脯氨酸(Hyp)水平及肝组织TSP-1(免疫组化法)表达量。[结果]模型组、自然恢复组大鼠肝纤维化程度、肝脏指数、血清HA和肝组织Hyp较正常组显著升高(P<0.05),肝组织中TSP-1的表达量显著上升,治疗组与模型组、自然恢复组比较肝纤维化程度明显改善,肝脏指数、HA、Hyp显著下降,肝组织中TSP-1表达量亦显著降低(均P<0.05)。[结论]银杏制剂对肝纤维化有良好的治疗作用,对大鼠肝纤维化肝组织中TSP-1的有效调节可能是抗肝纤维化的又一作用机制。     

蓝莓对免疫性肝纤维化大鼠肝组织TLR4,TLR9表达的影响

目的:探讨蓝莓抗氧化作用对猪血清免疫性肝纤维化大鼠肝组织Toll样受体4(toll-like receptor 4,TLR4)和Toll样受体9(TLR9)蛋白表达的影响.方法:60只♂Wistar大鼠随机分为正常对照组(A组)、模型组(B组)、蓝莓低、中、高剂量防治组(C、D、E组)、复方鳖甲软肝片防治组(F组).除A组外,其余各组均腹腔注射猪血清制备大鼠肝纤维化模型.C、D、E、F组在造模同时分别给予蓝莓原浆或复方鳖甲软肝片灌胃,1次/d,共12wk.第12周末处死大鼠,计算大鼠肝脏指数,行肝脏病理组织学检查,测定各组大鼠血清ALT和AST水平、肝组织匀浆超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)及羟脯氨酸(hydroxyproline,Hyp)含量,免疫印迹法(western blot,WB)和免疫组织化学法检测TLR4和TLR9蛋白质在肝脏组织中的表达.结果:各组大鼠血清ALT、AST水平无明显差异(F=4.274,0.917,P>0.05);与B组比较,D,E组肝组织匀浆SOD活性、GSH含量明显升高(F=6.662,61.472,P<0.05);肝脏指数、MDA及Hyp含量明显降低(F=3.972,42.755和41.265,P<0.05);肝纤维化程度明显减轻(F=63.339,P<0.05),胶原表达减少;E组大鼠肝组织TLR4和TLR9蛋白质表达明显减少(F=6.932和7.534,P<0.05).结论:TLR4和TLR9蛋白质表达增加可能与免疫性肝纤维化的发生发展有关.蓝莓对大鼠免疫性肝纤维化有一定的预防作用.     

黄芪注射液对血吸虫病肝纤维化小鼠血清透明质酸和肝组织羟脯氨酸含量的影响

目的:观察黄芪注射液对血吸虫病肝纤维化小鼠血清透明质酸和肝组织羟脯氨酸含量的影响。方法:将90只小鼠分成3组,感染组和黄芪注射液组每只小鼠感染日本血吸虫尾蚴30条,于感染后第35天用吡喹酮除虫,同时对黄芪注射液组小鼠用黄芪注射液处理。正常组不感染尾蚴。于感染后42天、63天、84天和105天分别取每组小鼠各5只,用酶联免疫法测定其血清透明质酸含量;用紫外分光光度法测定其肝组织羟脯氨酸含量。结果:黄芪注射液组小鼠在感染后第63天、84天、105天血清透明质酸含量显著低于同期感染组(P<0.05～0.01);在感染后第84天和105天肝组织羟脯氨酸含量显著低于同期感染组(P<0.01)。结论:黄芪注射液有一定预防血吸虫病肝纤维化的作用。     

大黄(庶虫)虫丸抗慢性肝损伤及肝纤维化作用的实验研究

本文以CCl_4等因素所致大鼠肝损伤、肝纤维化为模型,以血清ALT活性、Alb含量、肝Hyp含量、肝组织HE和胶原染色光镜观察等为观察内容,分预防和治疗实验观察大黄廑虫丸的防治作用,并设西药秋水仙碱组对照。结果表明:大黄廑虫丸有较显著的抗慢性肝损伤作用及一定的抗肝纤维化作用。在抗肝损伤,保护肝功能方面,较秋水仙碱为优;但在抗肝纤维化方面,尚不及秋水仙碱作用强。     

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.     

Effect of Danshao Huaxian capsule on expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in fibrotic liver of rats

AIM: To investigate the effects of Danshao Huaxian (DSHX) capsules, a preparation of traditional Chinese medicine, on the expression of matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the fibrous livers of rats. METHODS: Eighty male Wistar rats were randomly divided into normal control group (group A), CCl4-induced hepatic fibrosis group (group B), non-DSHX-treated group (group C), low dose-treated group (group D), and high dose-treated group (group E). Fibrous liver models in rats were induced by subcutaneous injection of CCl4, oral administration of alcohol and high-lipid/low-protein diet for 8 wk. After the models were established, the rats in groups D and E were orally given a low dose (0.5 g/kg) and a high dose (1.0 g/kg) of DSHX daily for 8 wk, respectively. Then, the liver indexes, serum hyaluronic acid (HA) and alanine aminotransferase (ALT) were examined. The degree of hepatic fibrosis was evaluated by optical microscopy. Hydroxyproline (Hyp) in the urine was determined, and the expression of MMP-1 and TIMP-1 was detected by immunohistochemical techniques. RESULTS: In groups D and E, the liver indexes, levels of serum HA and ALT reduced and development of hepatic fibrosis weakened significantly. The urinary Hyp and expression of MMP-1 in the liver tissues elevated, but the expression of TIMP-1 decreased obviously, as compared to groups B and C. CONCLUSION: DSHX enhances the expression of MMP-1 but decreases that of TIMP-1 in liver tissues of CCl4-induced hepatic fibrotic rats, which may result in its elevated activity that contributes to fighting against hepatic fibrosis.     

柔肝抑纤饮对血吸虫性肝纤维化小鼠肝组织病理形态的影响

目的：观察柔肝抑纤饮对肝纤维化小鼠肝组织病理形态的影响，并与秋水仙碱组进行比较。方法：将60只小白鼠随机分为5组：A组（空白对照组）、B组（感染未治疗组）、C组（吡喹酮组）、D组（柔肝抑纤饮组）、G组（秋水仙碱组）。除A组外，各组小鼠均感染血吸虫尾蚴，分别灌服相应药物，检测血清PCⅢ、HA，肝组织Hyp，行HE染色，光、电镜观察肝脏病理形态，肝组织胶原染色（VG），观察胶原纤维增生情况并测定百分比含量。结果：D组与G组小鼠在降低HA方面比较，差异无显著性意义（P〉0．05）；D组小鼠的PCⅢ、Hyp以及VG染色百分比含量显著降低，优于G组（P〈0.05）；D组与G组小鼠肝脏的病理表现明显轻于B组、c组，D组略优于G组。结论：柔肝抑纤饮能够明显抑制小鼠肝纤维化的形成，疗效不低于秋水仙碱。