甘肃产藏药五脉绿绒蒿有效部位对肝纤维化疗效和TGF-β1表达的影响

目的:观察甘肃产藏药五脉绿绒蒿有效部位对肝纤维化大鼠TGF-β1表达的影响.方法:在给药的基础上,采用sc CCl4、喂饲高脂低蛋白复合饲料并饮用20％乙醇来复制肝纤维化动物模型,6周后对大鼠肝组织免疫组化染色,检测TGF-β1的表达,同时检测血清中AST、ALT和TGF-β1的水平以及肝组织中Hyp的含量.结果:复合因素肝纤维化造模结束后,与模型对照组比较,甘肃产藏药五脉绿绒蒿醇提物、黄碱组以及总黄酮能明显降低血清ALT、AST以及肝组织中Hyp与胶原蛋白的含量,显著降低血清与肝组织中TGF-β1的表达,同时发现总黄酮的作用有一定的量效关系.结论:甘肃产藏药五脉绿绒蒿醇提物及其中的总黄酮对CCl4复合因素诱导的肝纤维化大鼠具较好的保护作用,对TGF-β1表达的抑制作用可能是其作用机制之一.     

熊果酸对肝纤维化大鼠NOX2/ROS/NLRP3炎性小体活化的影响

目的观察熊果酸(UA)对肝纤维化模型大鼠肝内胶原沉积的改善作用及其对NADPH氧化酶2(NOX2)/活性氧簇(ROS)/NLRP3炎性小体活化的影响。方法将大鼠随机分为对照组、CCl4模型组及UA治疗组。用CCl4诱导构建SD大鼠肝纤维化模型,一半用作UA治疗组。用试剂盒检测血清ALT含量;HE染色观察肝脏病理;天狼星红染色观察肝内胶原沉积;RT-q PCR法检测Nox2、Nlrp3、caspase1及IL-1βmRNA表达量;Western blot及免疫组化检测肝脏中NOX2、NLRP3、casepase-1 p45、caspase-1 p10及IL-1β蛋白表达;DCFH-DA荧光探针法检测肝脏组织内ROS水平。结果与对照组相比,CCl4模型组血清ALT水平升高(P0.05),Ishak's肝纤维化评分明显上升,胶原沉积明显增多(P0.05),Nox2、Nlrp3、Caspase1及IL-1βmRNA的表达水平明显上升(P0.05);NOX2、NLRP3、caspase-1 p10及IL-1β蛋白的表达均出现明显增加,肝组织内ROS含量增加(P0.05);与CCl4模型组相比,UA治疗组血清ALT含量下降(P0.05),肝脏Ishak's肝纤维化评分及胶原沉积减少(P0.05),Nox2、Nlrp3、caspase1及IL-1βmRNA的表达水平明显下降(P0.05),NOX2、NLRP3、caspase-1 p10及IL-1β蛋白表达明显下降,肝脏组织内ROS水平显著改善(P0.05)。结论 UA减轻肝脏炎性反应并减少肝内胶原沉积,其机制可能与其抑制肝纤维化大鼠肝内NOX2/ROS/NLRP3炎性小体活化及IL-1β的释放减少有关。     

红花黄色素对大鼠中毒性肝纤维化血清和肝组织HA和LN及胶原含量的影响

目的本实验以透明质酸(HA)、层粘连蛋白(LN)为指标,观察CCl4诱导大鼠中毒性肝损伤和肝纤维化后肝组织内储脂细胞变化和胶原的沉积及红花黄色素对其变化的影响,以探讨红花黄色素对中毒性肝纤维化防治作用的机制.方法Wistar大鼠随机分为3组①病理模型组接受40%CCl4一橄榄油皮下注射,剂量为1.2mL/kg体重,每周2次,共12周,与治疗组等容量生理盐水灌胃;②红花黄色素治疗组接受40%CCl4一橄榄油注射,方法、剂量同病理模型组,同时红花黄色素550mg/kg体重灌胃,每日1次,共12周;③正常对照组接受橄榄油皮下注射,方法、剂量同上.各组分别于实验开始后,每隔3周随机处死5只大鼠,剩余大鼠于12周末全部处死.断头采血,分离血清,取1g新鲜肝组织匀浆,用放免法测定大鼠血清和肝匀浆中HA、LN含量.肝组织V-G染色,用病理图像分析系统进行胶原定量分析.用透射电镜观察肝组织内储脂细胞变化.结果红花黄色素治疗组大鼠血清和肝匀浆中HA、LN含量及肝组织内胶原含量和储脂细胞变化显著低于病理模型组.结论红花黄色素能抑制肝脏储脂细胞增殖转化及HA、LN的合成,减少胶原沉积,有防治CCl4诱发中毒性肝纤维化的作用.     

实验性肝纤维化TGF-β1／Smad的表达及γ-干扰素对其的作用CSCD

目的观察Y-干扰索（IFN-Y）对四氯化碳（CCl4）诱导的大鼠肝纤维化的治疗效果,并探讨其可能的机制。方法30只雄性大鼠用CCl4诱导致肝纤维化,随机分成2组（模型组、IFN-Y治疗组）,连续用药12周,观察肝组织病理、血清透明质酸（hyaluronicacid,HA）、血清转化生长因子B,（transforminggrowthfactorβ1,TGF—β1）、肝组织切片TGF—β1、转化生长因子BI型受体（transforminggrowthfactorBreceptor,T13R·I）、Smad2/3,,的表达。结果①肝组织病理：与正常组比较,模型组大鼠肝组织都有不同程度的炎症和纤维化产生。模型组纤维化程度较正常对照组明显,差异有统计学意义（P〈0．05）;Y-干扰素治疗组纤维化程度较模型组显著改善,差异有统计学意义（P〈0．05）;②肝纤维化指标（HA、TGF—β1）：Y-干扰素治疗组大鼠HA及TGF—β1较模型组均降低（P〈0．05）,③TGF—β1／Smad基因蛋白：免疫组织化学检测显示,与模型组相比,IFN-Y治疗组大鼠肝脏中TGF-β1、TβR—I和Smad,蛋白表达均显著减弱,差异有统计学意义（P〈0．05）。结论IFN-Y治疗组具有显著抗肝纤维化作用,对TGF—β1／Smad信号转导通路的影响可能为其作用机理之一。     

慢性肾功能衰竭模型大鼠血清干细胞因子测定

背景：干细胞因子是一种多功能细胞因子,其可能参与了肾间质纤维化的发生发展。 目的：检测慢性肾功能衰竭大鼠模型血清干细胞因子水平,探讨其与大鼠肾间质纤维化发生发展的关系。 方法：健康雄性Wistar大鼠36只,随机分为2组,模型组用腺嘌呤灌胃诱发大鼠慢性肾功能衰竭,对照组用等量生理盐水灌胃。分别于实验第4、8和12周各组随机处死6只大鼠,检测血液学及尿液学指标,ELISA检测大鼠血清干细胞因子水平,苏木精-伊红、Masson染色观察大鼠肾间质纤维化程度,计算肾间质纤维化指数,分析大鼠血清干细胞因子浓度与肾功能及肾间质纤维化指数之间的相关性。 结果与结论：模型组大鼠各时期血清尿素氮、肌酐、干细胞因子水平及肾间质纤维化指数均明显高于对照组(P < 0.01),且上述指标均随着灌胃天数的延长逐渐增加,血清干细胞因子浓度与尿素氮、肌酐及肾间质纤维化指数均呈明显正相关(P < 0.01)。提示干细胞因子可能是慢性肾功能衰竭肾间质纤维化发生发展过程中的重要参与者。     

重组人肝再生增强因子可逆转免疫损伤性肝纤维化

目的:了解重组人肝再生增强因子(hALR)抗免疫损伤性肝纤维化的活性。方法:建立人血白蛋白免疫损伤性大鼠肝纤维化模型。模型完成后予hALR 腹腔注射。观察肝纤维化大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH)水平,肝组织胶原蛋白含量及肝脏病理学改变。结果:重组人肝再生增强因子(hALR)可降低肝纤维化大鼠的ALT、AST、LDH水平;肝组织胶原蛋白含量的测定表明hALR治疗组大鼠肝组织胶原含量明显低于模型组及阴性对照组;病理组织切片也发现hALR治疗组大鼠肝纤维化程度较模型组及阴性对照组明显减轻。结论:重组人肝再生增强因子(hALR)可逆转免疫损伤性大鼠肝纤维化。     

间-α胰蛋白酶抑制因子重链H1、α-2抗纤溶酶、运甲状腺素蛋白对肝纤维化的诊断价值及复方汉防己对其影响

目的:探讨间-α胰蛋白酶抑制因子重链H1(ITIH1)、α-2抗纤溶酶(SERPINF2)、运甲状腺素蛋白(TTR)对大鼠肝纤维化的诊断价值;以及复方汉防己对肝纤维化ITIH1、SERPINF2、TTR的影响.方法:Fisher344大鼠随机分为对照组,造模组,低、中、高剂量复方汉防己干预组.采用RT-PCR和免疫组织化学检测大鼠肝组织ITIH1、SERPINF2、TTR的mRNA及蛋白表达,ELISA法检测其血清含量.H-E染色、Masson三色染色、网状纤维染色观察肝纤维化程度.结果:造模组大鼠血清及肝组织中ITIH1、SERPINF2、TTR蛋白和mRNA的表达较对照组显著减少.复方汉防己干预组大鼠血清及肝组织中3者的表达较造模组均有不同程度升高.病理结果也显示复方汉防己干预组大鼠肝纤维化程度均有不同程度减轻.结论:ITIH1、SERPINF2、TTR对肝纤维化的分级诊断及病情监测具有一定的价值;复方汉防己能明显降低CCl4诱导的大鼠肝纤维化程度并能升高ITIH1、SERPINF2、TTR蛋白和mRNA的表达.     

丹芍化纤胶囊治疗大鼠肝纤维化后肝星状细胞凋亡及细胞周期的变化

目的：观察复方制剂丹芍化纤胶囊治疗大鼠CCl4中毒性肝纤维化对HSC细胞凋亡及细胞周期的影响，以探讨丹芍化纤胶囊可能的作用机理。 方法： 雄性Wistar大鼠采用CCl4、饮酒、高脂低蛋白饮食等复合病因刺激制备肝纤维化动物模型8周，然后给予丹芍化纤胶囊（1g/kg）灌胃治疗8周。实验结束时测定肝脏指数、血清透明质酸（HA）及谷丙转氨酶（ALT）含量，光镜下观察肝组织纤维化程度，检测尿羟脯氨酸（Hyp）排出量，同时用流式细胞仪检测治疗前后肝星状细胞（HSC）凋亡并分析细胞周期各期细胞比例。 结果： 治疗组大鼠的肝脏指数、血清HA、ALT含量明显低于肝纤维化模型组；肝纤维化程度明显轻于肝纤维化模型组；尿Hyp排出量显著高于肝纤维化模型组及自然恢复组；HSC细胞凋亡、G0-G1期细胞比例明显高于肝纤维化模型组（分别为7.81±0.47/0.28±0.05，94.30±1.33/68.40±6.47,P<0.05），S期细胞比例显著低于肝纤维化模型组及自然恢复组（分别为3.11±1.27，9.83±1.81，11.87±1.92，P<0.05）。 结论： 丹芍化纤胶囊对大鼠CCl4中毒性肝纤维化有一定的治疗作用，这种治疗作用可能部分是通过抑制HSC细胞增殖及促进HSC细胞凋亡而致。     

复方红景天防治肝纤维化的实验研究

目的研究复方红景天对四氯化碳诱导的大鼠肝纤维化肝组织TGF-β1基因表达的影响。方法80只SD大鼠随机分组:①空白对照组;②肝纤维化模型组;③复方红景天高剂量组(简称H组);④复方红景天中剂量组(简称M组);⑤复方红景天低剂量组(简称S组)。每组各16只。以CCl4腹腔注射法诱导大鼠肝纤维化,干预组大鼠在造模的同时给予复方红景天灌胃,正常对照组给予橄榄油皮下注射和生理盐水腹腔注射,8周实验结束时处死动物。酶联免疫吸附法检测血清TGF-β1水平,HE染色及免疫荧光观察大鼠肝组织病理学变化和胶原沉积,免疫组化法检测TGF-β1基因表达情况。结果治疗组大鼠肝组织内纤维组织及胶原沉积明显减少。结论复方红景天干预性治疗能够有效地减少大鼠肝组织胶原沉积,使其血清TGF-β1水平下降,并抑制TGF-β1基因表达,干扰TGF-β1介导的肝纤维化信号转导。     

槲皮素对四氯化碳诱导的大鼠肝纤维化抑制作用和肝保护作用

目的:探讨槲皮素对四氯化碳(CCl4)诱导大鼠肝纤维化的保护作用,并阐明槲皮素的抗肝纤维化机制.方法:Wistar大鼠随机分为5组:对照组、模型组、低剂量组(EXP-L)、中剂量组(EXP-M)、高剂量组(EXP-H).HE染色检测肝组织病理损伤情况;试剂盒检测谷丙转氨酶(ALT)和谷草转氨酶(AST)活力;羟脯氨酸(...     

雷公藤甲素抗肿瘤血管新生的研究进展（英文）

雷公藤甲素(triptolide,TPL)是从中草药雷公藤中提取的一种有效活性物质,已被用来治疗多种疾病,包括系统性红斑狼疮,类风湿性关节炎,肾病综合征等,TPL甚至有很强的抑制肿瘤的活性。近些年的研究显示,TPL具有抗血管新生的能力,TPL不仅可以抑制肿瘤的增殖,诱导细胞的凋亡,还可以抑制肿瘤的转移,可以增加其它化疗药物的抗肿瘤活性。本综述将讨论TPL在抗肿瘤血管新生方面的研究进展,以及初步探讨其潜在的作用机制。     

Changes in activity of neutral proteases in tissues of ground squirrels in the dynamics of hibernation

Total activities of neutral proteases in the cerebral, hepatic, and myocardial tissues of ground squirrel vary during hibernation: in autumn (before hibernation) activities of the enzymes in the brain and myocardium start increasing, while in the liver they do not change. A common feature for all tissues is minimum activity of active neutral proteases in the middle of hibernation month 1 bout, while the maximum activity is recorded before awakening. Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 146, No. 9, pp. 278–280, September, 2008     

Kinetics of decline of maternal measles virus-neutralizing antibodies in sera of infants in France in 2006

The optimal age for measles vaccination is an important health issue, since maternal antibodies may neutralize the vaccine antigen before a specific immune response develops, while delaying vaccination may increase the risk of complicated diseases in infants. However, measles vaccination impacts the duration of protection afforded by transplacental transfer of maternal antibodies: vaccination-induced maternal antibodies disappear faster than disease-induced antibodies. In order to maintain protection against measles in infants, it is important to monitor the dynamics of this phenomenon in vaccinated populations. To assess the current situation in France, a multicenter, prospective seroepidemiological study was conducted in seven French hospitals between October 2005 and January 2007. Maternal measles antibody concentrations from 348 infants 0 to 15 months old were measured using the plaque reduction neutralization assay. Geometric mean concentrations and the percentage of infants with maternal measles antibody concentrations above the protection threshold (≥120 mIU/ml) were assessed according to age. Results show that after more than 20 years of routine measles vaccination in France, maternal measles-neutralizing antibodies decrease dramatically in French infants by 6 months of age, from 1,740 mIU/ml for infants 0 to 1 month old to 223 mIU/ml for infants 5 to 6 months old, and that 90% of infants are not protected against measles after 6 months of age. Infant protection against measles could be optimized both by increasing herd immunity through an increased vaccine coverage and by lowering the age of routine vaccination from 12 to 9 months.     

Effect of vitamin C in reducing the toxicity of endosulfan in liver in rabbits

In this study, the effect of endosulfan, an organochlorine pesticide, and the ameliorating effect of vitamin C on the livers of New Zealand white rabbits were studied. Livers of the rabbits were examined grossly and histopathologically, and caspase-3 activity was detected by immunohistochemical methods. A total of twenty-four rabbits were divided into four groups (n=6). Rabbits in Group I (END) were daily given a sublethal dose of endosulfan (1 mg/kg bw) in corn oil by oral gavage for 6 weeks. Group II (END+C) received the same dose of endosulfan and additionally Vit C (20 mg/kg bw) every other day during this period. Group III (OIL+C) received corn oil daily by oral gavage and vitamin C every other day for 6 weeks. Group IV (OIL), the control group, received only corn oil daily, by oral gavage throughout the experiment. The concentration of α-endosulfan in the END group was higher in livers (0.102±0.012 ppb) than the β-endosulfan (0.072±0.001 ppb). Decreased accumulation of α and β endosulfan was observed in the END+C group (0.025±0.003 and 0.016±0.002 ppb, respectively) (p<0.0001). The most prominent gross findings at the necropsy were seen in the END group, in which swollen and pale livers were commonly observed. Hemorrhages, degenerations, necrosis, and in some rabbits bile duct hyperplasia were the marked histopathological findings of the END group. Caspase-3 positive reaction was more severe in this group than in the others. An ameliorating effect of Vit C on gross, histopathological and immunohistochemical findings was observed in the END+C group. The results revealed that endosulfan is highly toxic for rabbit livers. However, toxicity was decreased by Vit C treatment, which reduced the accumulation of endosulfan in livers four-fold.