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目的:观察雷公藤甲素引起急性肝损伤时肝细胞自噬的情况。方法:采用LC3-GFP质粒尾静脉高压注射的方法在体监测雷公藤甲素诱导肝细胞自噬的发生;用腺病毒双荧光载体m RFP-GFP-LC3感染体外培养的HepG2细胞,通过激光共聚焦显微镜和蛋白印记的方法检测细胞自噬流的强度。结果:小鼠腹腔注射雷公藤甲素(0.25 mg/kg和0.5 mg/kg)24小时,血清中ALT和AST水平均显著升高;肝组织病理结果显示肝细胞肿胀、空泡化及坏死;激光共聚焦显微镜下可检测到LC3-GFP质粒表达所呈现的绿色荧光;离体细胞实验结果证实雷公藤甲素可诱导肝细胞发生自噬流,且表现为一定程度的剂量、时间依赖性。结论:雷公藤甲素可引发急性肝损伤并伴随明显的细胞自噬。 相似文献
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摘要 目的:观察雷公藤甲素诱导肝细胞选择性自噬的水平。方法:在雷公藤甲素给药处理小鼠的尾静脉高压注射GFP-LC3质粒,制备肝细胞自噬示踪模型,观察雷公藤甲素在动物体内诱导肝细胞自噬的水平。在GFP-LC3稳定表达的L02细胞株中转入RFP-P62质粒,用活细胞工作站和荧光显微镜动态观察雷公藤甲素诱导L02细胞选择性自噬的轮廓,同时也观察细胞自噬复合体LC3-P62的变化。结果:动物实验结果表明,雷公藤甲素可显著诱导肝细胞自噬体的形成,Western blot结果显示P62蛋白和LC3II蛋白的表达趋势一致。活细胞动态观察及免疫荧光双标记实验结果表明LC3-P62存在共定位,提示雷公藤甲素可诱导肝细胞自噬流的形成。结论:雷公藤甲素可诱导肝细胞选择自噬,其生物学意义可能与肝细胞损伤后修复相关。 相似文献
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《天然产物研究与开发》2017,(3)
本文研究雷公藤甲素致肝损伤作用机制。将雌性C57BL/6小鼠20只随机分为2组,并以雷公藤甲素造模,通过检测血清中谷丙转氨酶(ALT)水平变化,以及观察小鼠肝脏组织切片HE染色结果,了解肝脏损伤情况;RT-PCR法检测小鼠肝脏中白细胞介素(IL)-17、IL-6、维甲酸孤儿核受体(ROR-γt)mRNA表达水平,ELISA法检测IL-17、IL-6蛋白表达水平,Western blot法检测小鼠肝脏中TLR4蛋白表达水平。与对照组比较,雷公藤甲素模型组小鼠血清ALT水平显著升高(P0.005),HE染色切片显示较多的肝细胞坏死和炎症细胞浸润,IL-17、IL-6、ROR-γt mRNA表达水平和IL-17、IL-6蛋白表达水平显著升高(P0.005),此外,TLR4蛋白表达水平显著升高(P0.005)。结果表明,雷公藤甲素所导致的肝损伤可能通过激活TLR4信号,增加IL-17、IL-6的表达,影响Th17特异性转录因子ROR-γt,进而促进Th17细胞活化,增强其致炎功能。 相似文献
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摘要 目的:探究雷公藤甲素(Triptolide)对刀豆蛋白A(Concanavalin, Con A)诱导的小鼠急性肝损伤的保护机制。方法:雄性BALB/c小鼠30只,随机等分为正常对照组、Con A模型组和雷公藤甲素治疗组。通过尾静脉注射Con A构建小鼠急性肝损伤模型。微孔板法检测血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平,HE染色观察肝组织病理变化,免疫组化、实时荧光定量PCR(RT-qPCR)和酶联免疫吸附试验(ELISA)检测肝组织及血清中细胞因子水平。结果:与正常对照组比较,Con A诱导急性肝损伤小鼠血清ALT、AST水平显著增高(P<0.05),肝组织呈局灶性炎性浸润、坏死。与Con A模型组比较,雷公藤甲素治疗组小鼠血清ALT、AST水平显著下降(P<0.05);肝组织病理程度明显减轻;肝组织中CD4+T细胞的浸润降低,促炎细胞因子(IFN-γ、TNF-α、IL-1β、IL-2)的水平显著降低(P<0.05)。结论:雷公藤甲素可以通过抑制CD4+T细胞向肝脏募集,下调IFN-γ、TNF-α、IL-1β、IL-2的表达,有效防治Con A诱导的急性免疫性肝损伤。 相似文献
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自噬与凋亡被认为是细胞程序性死亡的两种重要途径,二者的交互联系对阐明药物的抗肿瘤机理有重要价值.众多的研究表明,雷公藤甲素对多种肿瘤细胞都具有显著的抑制作用.细胞凋亡与自噬可被相同的因素所诱导,p53蛋白可以同时对二者起调控作用,在自噬与凋亡的交互作用(crosstalk)中扮演着重要角色.本文以He La细胞为模型,研究雷公藤甲素诱导He La细胞发生自噬和凋亡的机制,并通过抑制p53依赖的转录,研究雷公藤甲素诱导He La细胞p53依赖的自噬和凋亡交互联系. 相似文献
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《基因组学与应用生物学》2017,(4)
探讨腺苷酸活化蛋白激酶(AMP activated protein kinase,AMPK)激活剂A-769662对肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)诱导的爆发性肝损伤中肝细胞凋亡的影响及机制。本研究在雄性BALB/c小鼠经腹腔内注射肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)及D氨基半乳糖胺(D-galactosamine,D-Gal),诱导爆发性肝炎模型。实验分为4组:正常对照组、A-769662单独处理组、模型组和A-769662干预组。采用比色法检测血浆转氨酶活性及肝组织中caspase-8、caspase-9、caspase-3的相对活性,Western blotting法检测肝组织中激活型caspase-3蛋白水平,TUNEL法检测肝细胞凋亡,HE染色观察肝组织病理变化,并记录各组小鼠生存情况。A-769662干预抑制了TNF-α/D-Gal诱导的肝组织中caspase-8、caspase-9、caspase-3的活性和激活型caspase-3蛋白表达水平的升高,显著减少肝细胞凋亡数目,明显下调血浆中天冬氨酸氨基转氨酶(aspartate transaminase,AST)与丙氨酸氨基转氨酶(alanine transaminase,ALT)水平,减轻肝组织病理学改变,提高小鼠生存率。AMPK激活剂A-769662在TNF-α诱导的爆发性肝损伤中,可发挥抗凋亡保护效应,这可能是其在保肝效应的新机制。 相似文献
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目的:探讨海兔素对刀豆蛋白A诱导的化学性肝损伤保护作用。方法:雄性Wistar大鼠随机分为4组。模型组与海兔素组给予15 mg/kg刀豆蛋白A尾静脉注射每周一次,制作化学性肝损伤模型,模型制作成功后,正常对照组、模型组每日给予大豆油灌胃,海兔素低、高剂量组给予100、150 mg/kg·d海兔素+大豆油灌胃。实验持续8周后,禁食12 h,处死大鼠。HE染色观察肝组织形态学改变;Masson Trichrome及天狼星红染色观察肝组织纤维化状况;全自动生化分析仪检测血清ALT、AST及LDH水平;ELISA实验测定血清TNF-α和TGF-β1水平。结果:与正常对照组相比,模型组大鼠肝小叶结构模糊紊乱,纤维组织增生明显,可见灶状坏死及炎性细胞浸润,胶原纤维明显增多,胶原指数明显升高。血清中ALT、AST、LDH及TNF-α和TGF-β1水平显著升高(P0.05)。海兔素干预后,肝小叶病变程度较模型组明显减轻,染色胶原显著减少,纤维增生明显改善,血清中ALT、AST、LDH及TNF-α和TGF-β1水平较模型组显著降低(P0.05),海兔素高剂量组与低剂量组相比,肝脏病变改善程度更为明显(P0.05)。结论:海兔素对刀豆蛋白A诱导的化学性肝损伤具有一定保护作用,其机制可能与下调TNF-α、TGF-β1水平有关。 相似文献
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目的本实验主要研究冬凌草甲素诱导多发性骨髓瘤发生自噬、凋亡,两者之间的关系以及所涉及的相关机制。方法利用MTT比色法检测冬凌草甲素对多发性骨髓瘤RPMI8226细胞的增殖活性影响;透视电镜观察细胞内凋亡和自噬的形态学改变;TUNEL检测细胞凋亡;分别利用以下技术检测处理后的细胞内的自噬变化:使用QDs605nm-Anti-LC3荧光探针以及免疫荧光技术定位细胞胞内LC3Ⅰ和LC3Ⅱ蛋白,利用western blot免疫印记技术检测Beclin 1蛋白表达水平;利用DCFH-DA探针以及流式细胞术检测细胞胞内ROS水平。结果冬凌草甲素能明显抑制RPMI8226细胞增殖,其抑制作用呈时间、剂量依赖性;冬凌草甲素能同时诱发细胞凋亡、自噬和胞内ROS产生;NAC完全抑制胞内ROS产生后冬凌草甲素诱导的细胞凋亡消失;3-MA抑制自噬后,冬凌草甲素诱导的胞内ROS产生进一步增多,凋亡增多。结论冬凌草甲素能明显抑制RPMI8226细胞增殖;冬凌草甲素同时诱发细胞凋亡和自噬;胞内ROS产生介导冬凌草甲素诱导的凋亡;凋亡为细胞死亡的主要途径,而自噬通过下调胞内ROS产生抑制凋亡。 相似文献
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雷公藤甲素诱导胰腺癌细胞凋亡 总被引:2,自引:0,他引:2
目的:观察雷公藤甲素对胰腺癌细胞BxPC-3和PANC-1生长抑制及诱导细胞凋亡作用,探讨雷公藤甲素抗胰腺癌的机制。方法:雷公藤甲素处理BxPC-3和PANC—1细胞后,用M1rr法检测细胞的生长抑制,用流式细胞术检测细胞的凋亡率,用罗丹明123和DCFH—DA染色方法测定细胞线粒体膜跨膜电位变化和活性氧(ROS)的产生,用Western印迹检测Bcl-2、Bax蛋白表达的变化。结果:雷公藤甲素对胰腺癌细胞BxPC-3和PANC—1具有生长抑制和诱导细胞凋亡的作用,且呈时间和剂量依赖关系;处理72h后,胰腺癌细胞线粒体跨膜电位明显下降,Bax表达上调,Bcl-2表达下降。结论:雷公藤甲素能有效抑制胰腺癌细胞增殖,通过增强线粒体通透性诱导细胞凋亡。 相似文献
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CCl4和脂多糖诱导的急性肝损伤中肝细胞凋亡病理特点比较 总被引:1,自引:0,他引:1
目的比较CCl4和脂多糖诱导的两种急性肝损伤模型中肝细胞凋亡的病理特点。方法雄性BABL/c小鼠随机分为正常组、CCl4模型组与脂多糖模型组。CCl4和脂多糖模型小鼠分别腹腔注射0.03 mL/kg 50?l4/橄榄油混合液和10μg/kg脂多糖与900μg/kg半乳糖胺。9 h后采集标本,检测肝细胞凋亡,血清ALT、AST活性,肝组织SOD活性、MDA含量。结果与正常组比较,CCl4和脂多糖模型小鼠血清ALT与AST活性均明显升高(P<0.01),且脂多糖模型高于CCl4模型(P<0.01);模型小鼠均有明显肝细胞凋亡(P<0.01),且两组间无显著差异,但CCl4模型呈局灶性,以中央静脉周围为主;脂多糖模型呈弥漫性,肝细胞坏死与肝组织炎症更显著(P<0.01)。CCl4和脂多糖模型肝组织均SOD活性升高、而MDA含量下降(P<0.01),但CCl4模型更显著(P<0.05)。结论CCl4与脂多糖诱导的急性肝损伤小鼠模型均有明显的肝细胞凋亡,但CCl4模型以中央静脉区为主,脂质过氧化损伤更为明显;脂多糖模型呈弥漫性,肝细胞坏死与肝组织炎性反应较重。 相似文献
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Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis
It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis. 相似文献
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RICHARD E. NORRIS 《Botanical journal of the Linnean Society. Linnean Society of London》1991,106(1):1-40
Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera. 相似文献
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JOAN VALUÈS MONTSERRAT TORRELL NÚRIA GARCIA JACAS 《Botanical journal of the Linnean Society. Linnean Society of London》2001,137(4):399-407
Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted. 相似文献
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肝癌中HBV和HCV基因和抗原的分布及意义 总被引:1,自引:0,他引:1
采用原位分子杂交方法检测HCV
RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV
RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV
RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV
X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV
C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细 相似文献
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H.-R. GREGORIUS 《Biological journal of the Linnean Society. Linnean Society of London》1984,23(2-3):157-165
For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment. 相似文献
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment. 相似文献