TGF-β诱导CTGF表达的信号转导途径及与纤维化形成

转化生长因子-β(transforming growth factor-β,TGF-β)是一种具有多重生物学效应的细胞因子,参与了多种组织器官纤维化的形成。结缔组织生长因子(connective tissue growth factor,CTGF)是一种富含半胱氨酸的多肽,是介导TGF-β致纤维化作用的重要下游因子之一。TGF-β可通过多种信号途径诱导CTGF表达,本文就这一领域的研究进展及与纤维化形成的关系做一简要综述。     

激动素对大鼠肝纤维化后TGF—β1和CTGF变化的影响

目的 检测激动素（kinetin）对大鼠肝纤维化后转化生长因子β1（transforming growthfactor-β1,TGF-β1）和结缔组织生长因子（connective tissue growth factor,CTGF）含量变化的影响。方法将大鼠随机分为3组,模型组,用CCl4诱导形成肝纤维化模型;激动素组,CCl4造模同时给予0．1％激动素溶液0．5ml／100g／d（每天每100克体重大鼠注射0．5ml0．1％激动素溶液）皮下注射;对照组,给予生理盐水皮下注射,治疗12周。应用免疫组化和图像分析技术对3组中TGF-β1和CTGF含量及分布特点进行观察。结果激动素组TGF-β1为（1．339±0．244）％较模型组（1．904±0．367）％显著降低（P〈0．01）,CTGF为（2．689±0．534）％较模型组（4．242±1．612）％显著降低（P〈0．01）,上述两组TGF-β1和CTGF含量较正常对照组（0．926±0．277）％和（1．608±0．644）％显著升高（P〈0．01）。结论 激动素对实验性大鼠肝纤维化具有抑制作用。     

转化生长因子-β与器官纤维化

本文综述了转化生长因子-β(TCF-β)的生物学效应、信号转导途径、影响其效应的因素、TGF-β在器官纤维化中的作用以及围绕TGF-β信号转导途径所进行的抗纤维化治疗的最新进展。     

瘦素和转化生长因子β1在大鼠肝纤维化过程中的作用

目的探讨瘦素和转化生长因子β1（transforming growthβ1,TGF-β1）在肝纤维化发生、发展过程中的作用。方法雌性Wistar大鼠随机分为正常对照组和纤维化模型1周组、2周组、4周组、6周组。纤维化模型各组以CCl4造成化学性肝损伤。常规HE染色观察肝脏病变;检测血浆和肝组织瘦素及TGF-β1水平;天狼猩红胶原染色和肝组织羟脯氨酸（Hyp）含量测定观察肝纤维化程度,并对肝组织瘦素水平、TGF-β1水平及肝纤维化指数（FI）进行相关性分析;赖氏法测定血浆丙氨酸氨基转移酶（ALT）。结果与正常对照组比较,纤维化模型各组血清和肝组织瘦素和TGF-β1水平显著升高（P〈0.05）,且纤维化模型各组肝组织瘦素水平、TGF-β1水平及FI之间两两均呈显著正相关。结论肝组织瘦素在肝纤维化发病过程中具有独立的致病作用,并可能通过激活TGF-β1通路导致肝维化的形成。     

转化生长因子TGF-1β1／结缔组织生长因子CTGF对骨创伤愈合的调控机理研究

转化生长N子TGF—β1和结缔组织生长因子CTGF是骨形成过程中不可或缺的重要生长因子。研究发现TGF-β1和CTGF具有协同生物效应,CTGF可能作为TGF-β1的下游信号发挥作用。本文对近年来TGF-β1／CTGF通路在骨发育与创伤愈合中相关信号转导调控及分子机制研究进行讨论。尤其是对成骨细胞增殖、分化和功能的调控机理进行综述。     

川芎嗪对转化生长因子β1刺激肝星状细胞CTGF及I型胶原表达的影响

研究川芎嗪对大鼠肝星状细胞株（hepatic stellate cell—T6,HSC—T6）结缔组织生长因子CTGF（connec tivetissue growth factor）及I型胶原表达的影响．培养HSC—T6细胞,不同浓度川芎嗪与转化生长因子-β1（transforming growth factor-β1,TGF-βl）刺激的HSC—T6共同孵育．用MTT（3-（4,5-Dimethyhhiazol-2-yl）-2,5-diphenyltetrazolium bromide）法检测HSC-T6增殖：免疫细胞化学法观察川芎嗪对CTGF表达的影响;Western印迹法检测CTGF蛋白的表达．ELISA（enzyme linked immunosorbent assay）法测定I型胶原表达．结果表明,一定浓度（100、200、400、600mg／L）川芎嗪能抑制HSC—T6增殖,且呈剂量依赖性．免疫细胞化学结果显示随着川芎嗪浓度的升高,CTGF表达依次递减,与正常对照纽比较,具有显著性差异（t=4．216,P〈0．01）．川芎嗪还可以明显抑制CTGF蛋白的表达,并可抑制I型胶原合成,二者抑制程度呈正相关关系（r=0．861,P〈0．01）．川芎嗪可能通过抑制HSC—T6细胞增殖,下调CTGF的表达,阻断I型胶原合成,从而发挥其抗肝纤维化的作用．     

HSC的活化、增殖与TGF-β1及其Ⅰ型受体在中晚期纤维化肝组织中的改变及护肝片对其的影响

目的 探讨护肝片对中、晚期纤维化大鼠肝组织肝星状细胞（HSC）的活化与增殖及转化生长因子-β1（TGF-β1）及其工型受体（TβRⅠ）表达的影响。方法 采用12．5％CCh诱导的大鼠肝纤维化模型,自造模之日起,大鼠分组灌胃给药（护肝片921mg·kg^-1）或溶媒,每日一次,直至8或13周末,分别处死动物,取左叶肝组织石蜡包埋,制作组织芯片,免疫组化S-P法检测大鼠肝组织α-平滑肌肌动蛋白（α-SMA）、TGF-β1及TβRⅠ蛋白的表达,并用Meta Morph图像分析系统计数α-SMA阳性细胞数、对TGF-β1。及TβRⅠ蛋白表达量进行定量分析。结果 1．模型复制8周和13周,模型组的肝损伤及其纤维化分级均明显高于正常组（P〈0．01）,护肝片组的肝损伤及其纤维化分级均轻于模型组。2．模型复制8周和13周,模型组活化的HSC（即α-SMA阳性细胞）数量较正常组明显增多、TGF-β1及TβRⅠ蛋白的表达较正常组明显增强（P〈0．01）;3．护肝片显著抑制8、13周纤维化肝组织HSC的活化与增殖和TGF-β1及TβRⅠ蛋白的表达（P〈0．01）。结论 抑制HSC的活化与增殖和TGF-β1及TβRⅠ的表达可能是护肝片抗肝纤维化作用的靶点之一。     

肝心宁对肝纤维化大鼠肝组织病理及PDGF-BB、TGF-β、MMP-1的影响

目的：从肝纤维化的病理学和血清标志物方面,探讨肝心宁对肝纤维化大鼠肝组织病理的影响。方法：将60只SD大鼠随机分成正常对照组,肝纤维化模型组和肝心宁干预纤维化组。采用改良式复合因素法复制大鼠肝纤维化模型。正常对照组与肝纤维化模型组给予生理盐水10mL/kg灌胃,肝心宁干预纤维化组给予10g/kg治疗。6周后,取各组大鼠肝脏组织,HE染色比较各组大鼠肝脏组织的病理学变化,检测比较不同组大鼠血清中肝纤维化指示物血小板生长因子-BB（PDGF-BB）、转化生长因子-β1（TGF-β）、基质蛋白酶-1（MMP-1）的含量。结果：肝组织病理学：与肝纤维化模型组相比,干预组炎症坏程度减轻,肝纤维化程度明显改善,血清PDGF-BB、TGF-β1含量显著下降,而MMP-1含量显著升高。结论：肝心宁能有效改善肝纤维化血清学指标和病理学指标。     

柞蚕雄蛾液对酒精肝纤维化小鼠的预防作用及其机制研究

目的:观察柞蚕雄蛾液对酒精诱导的小鼠肝纤维化的预防作用并探讨其可能的机制。方法:选择40只SPF级C57BL/6J小鼠,随机分为对照组、模型组、柞蚕雄蛾液低剂量组、柞蚕雄蛾液高剂量组,每组各10只。除对照组外,其他各组均通过酒精灌胃建立酒精性肝纤维化模型。柞蚕雄蛾液低剂量组、柞蚕雄蛾液高剂量组每天先予柞蚕雄蛾液灌胃,两小时后予以酒精灌胃。16周后,所有小鼠禁食12 h后通过眼球取血后处死,取出肝脏。采用HE和Masson染色观察肝组织病理改变并进行肝纤维化分级;检测血清中ALT及AST的含量,免疫组化法检测肝组织转化生长因子β1(TGF-β1)、基质金属蛋白酶抑制剂-1(TIMP-1)、结缔组织生长因子(CTGF)的表达,Western blot法测定肝组织中Smad2/3的蛋白表达。结果:柞蚕雄蛾液低剂量组镜下只见少量点状坏死和炎细胞浸润,肝组织损伤比模型组明显减轻。与对照组比较,模型组TGF-β1、TIMP-1、CTGF、Smad2/3的表达均明显增高(P0.001),血清ALT及AST水平显著升高(P0.001);与模型组比较,柞蚕雄蛾低剂量组TGF-β1、TIMP-1、CTGF、Smad2/3表达明显降低(P0.001),血清ALT及AST水平显著下降(P0.001)。结论:柞蚕雄蛾液对酒精诱导的小鼠肝纤维化具有显著的预防作用,低剂量柞蚕雄蛾液较高剂量柞蚕雄蛾液可能更有效,其机制可能与调控TGF-β1/Smad2/3信号转导通路,下调TIMP及CTGF抑制HSC的活化与增殖有关。     

胆道闭锁患儿肝组织TGF-β1、CD34在肝纤维化中的作用及血清TGF-β1的诊断价值研究

摘要 目的：探讨转化生长因子-β1（transforming growth factor-β1，TGF-β1）和白细胞分化抗原34（Cluster of Differentiation，CD34）在胆道闭锁患儿肝组织中的表达及在肝纤维化中的作用，验证血清TGF-β1浓度对该病患儿肝纤维化的诊断价值。方法：选取2016年4月-2019年1月我院收治的胆道闭锁（Biliary atresia，BA）患儿66例作为研究组、胆管扩张症患儿30例作为对照组，比较两组肝组织中TGF-β1及CD34因子的免疫组化检测结果，以及研究组不同肝纤维化分级患儿的TGF-β1及CD34因子表达情况及其与肝纤维化分级的相关性。比较两组血清TGF-β1浓度，以及研究组不同肝纤维化分级患儿血清TGF-β1浓度情况及其与肝纤维化分级的相关性，最后绘制ROC曲线检测血清TGF-β1浓度对该病患儿肝纤维化的诊断价值。结果：研究组肝组织TGF-β1 IOD值及CD34因子表达面积均高于对照组，差异有统计学意义（P＜0.05）；随着研究组患儿的肝纤维化程度不断加重，TGF-β1及CD34因子的阳性表达率均不断增加，差异有统计学意义（P＜0.05），且分别与肝纤维化程度呈正相关（ρ=0.594，P＜0.05；ρ=0.616，P＜0.05）。研究组血清TGF-β1浓度高于对照组，差异有统计学意义（P＜0.05）；随着研究组患儿肝纤维化程度不断加重，血清TGF-β1浓度不断增加，差异有统计学意义（P＜0.05），且与肝纤维化程度呈正相关（ρ=0.944，P＜0.05）。血清TGF-β1对胆道闭锁患儿肝纤维化有诊断意义（AUC=0.917，P＜0.001），诊断的最佳界值为436.4 ng/L（敏感度为0.879，特异度为0.867）。结论：TGF-β1及CD34在胆道闭锁患儿肝组织的表达显著升高，提示可能通过抑制患儿TGF-β1及CD34表达进而阻止或延缓胆道闭锁所致肝纤维化进展；血清TGF-β1可用于诊断患儿胆道闭锁所致肝纤维化。     

Sex-specific somatic–otolith growth relationship in two Gadidae

Otolith and somatic mass of two Gadidae ( Merlangius merlangus and Trisopterus minutus ) were compared in order to analyse the sex-specific relationship between otolith and somatic growth at age. In the present study, otolith mass appeared a reliable indicator of age in both species. Otolith growth reflected somatic growth, but the relationship between these characters varied and differed between species and sexes.     

Control of animal cell proliferation

Present understanding of the control of animal cell proliferation is summarized briefly. Major gaps in present knowledge are listed. Models of growth control are discussed.     

生长激素分泌促进剂及构效关系研究进展

生长激素分泌促进剂是一类作用于垂体和下丘脑的具有专一性促生长激素释放作用的寡肽及其类似物.由于其分子质量小、活性高、可口服、作用专一而有可能成为新的生长激素治疗药物.目前已经发展了很多具有此类活性的多种结构的化合物,如肽、环肽、肽醇及非肽类似物等.尽管这类化合物的作用机制尚未完全明确,但已有证据表明存在新的调节生长激素分泌的途径和新的调节因子.     

Light-, nitrogen-, and phosphorus-limited growth of Phaeodactylum tricornutum Bohlin strain TFX-1: Chemical composition,carbon partitioning,and the diel periodicity of physiological processes

Phaeodactylum tricomutum Bohlin (strain TFX-1) was grown under light-, nitrogen-, and phosphorus-limited conditions in continuous or semicontinuous cultures under a 12L-12D light regime. The C, N, and P contents were determined at each steady state, as was the partitioning of cellular organic carbon into protein, lipids, polysaccharides, and metabolic intermediates. All determinations were made at the beginning and again at the end of the light period. The rates of nutrient assimilation and of synthesis of biochemical constituents during the light and dark periods were calculated from the above data, and the periodicities of these processes characterized. The elemental composition of the cells was different under each limitation. In particular, phosphorus limitation severely restricted the ability of the cell to store nitrogen in non-protein forms. Biochemical composition and the diel periodicity of cellular processes also differed between limitations. Nutrient uptake was most strongly periodic under light limitation. Protein synthesis showed increased periodicity under nitrogen limitation, relative to the other limitations, while the periodicity of lipid synthesis was reduced under phosphate limitation. Polysaccharide was synthesized at high rates during the light period and consumed in the dark under all limitations.     

The growth ring concept: seeking a broader and unambiguous approach covering tropical species

The concept of growth rings is little discussed in the literature and their treatment remains somewhat confusing in terms of the diversity of structures described. This situation has a major impact on the study of growth rings in tropical species, in which variations and complexity are greater and accuracy of identification less good. The rigid conceptual delimitations used by dendrochronologists and wood anatomists of temperate regions cannot be applied to the study of growth rings in most tropical species, which has led to neglect of this subject. With the objective of discussing the concept of growth rings, the present study consists of a survey of anatomical, periodicity, causal and evolutionary aspects of the treatment of these structures as evidenced in previous studies, and the evaluation of their application and limitations to the development of this concept. Anatomical aspects arise through radial integrity, or the presence of early and late wood; the degree of distinction of the rings, which may vary from well to poorly defined; and tangential continuity, meaning that rings may form a complete circle in the transverse section of the trunk, or instead be tangentially discontinuous, lens‐shaped or in wedges. In addition there are a diversity of anatomical markers which enable us to recognize growth rings. Regarding periodicity, the rings may be annual, infra‐annual or supra‐annual. Causal aspects include genetic, endogenous and environmental components. Evolutionary aspects continue to be insufficiently investigated, and although most comparative studies treat growth rings recognized by different markers as though they were a single character, it remains questionable whether they can be regarded as homologous or the result of homoplasy. We conclude that the elaboration of a robust but broad definition which can include all the variation observed in growth rings of tropical species is a complex task, which is only possible by overcoming the restrictions adopted by dendrochronologists and wood anatomists of temperate regions for whom growth rings are essentially annual, strongly demarcated, tangentially continuous and restricted to the most pronounced markers.     

Validation and implications of a growth model for brown trout, Salmo trutta, using long-term data from a small stream in north-west England

Summary 1. The objectives were: (i) to check the validity of a new growth model; (ii) to examine the relationship between population density and both mean mass and mean growth rate and (iii) to discover if compensatory growth occurred. First (0+) and second (1+) year‐old juvenile sea‐trout were sampled by electrofishing at the beginning and end of the summer from 1967 to 2000. Additional samples were taken in some years in winter and in the critical period for survival when the fry first emerge from the gravel. The trout left the stream as pre‐smolts in May, soon after their second birthday. 2. A growth model ( Elliott, Hurley & Fryer, 1995 ) estimated the mean mass of the trout over the 2 years spent in fresh water. The date and mean mass at the start of the growth period were defined as the median date for fry emerging from the gravel and their mean mass at emergence, both being estimated from individual‐based models ( Elliott & Hurley, 1998a, b ). 3. The variation in mean mass among year‐classes was small for newly‐emerged fry (CV = 6.2%), maximum at the start of the first summer of the life cycle (CV = 38.1%), and then decreased gradually for successive life‐stages to a low value for pre‐smolts (CV = 10.8%). Mean mass was not related to population density and, therefore, mean growth rate was density‐independent. Growth in the first, but not the second, winter of the life cycle was lower than model prediction, but when it was assumed in the model that there was no first‐winter growth, there was good agreement in most year‐classes between model estimated values and observed mean mass. Exceptions were that mean masses and growth rates for 0+ trout after four summer droughts were lower than expected, but compensatory growth followed, so that observed and expected masses were similar for 1+ trout. 4. Pre‐smolt mean mass on 30 April measured total growth achieved in the freshwater phase of the life cycle. This was significantly related to mean mass at the end of the first and second summers of the life cycle, but not to the emergence date and mean mass of emerging fry. 5. These juvenile sea‐trout were growing at their maximum potential in most year‐classes but when this was not achieved, compensatory growth soon restored their mass to values expected from the model. This ensured a low variation in the mean mass of pre‐smolts just before they migrated to the sea. However, the latter mass was higher in more recent year‐classes (1987–98) than in previous ones (1967–86), demonstrating the effect of slightly higher stream temperature. This study has shown the importance of developing realistic growth models in order to detect departure from maximum potential growth, and the more subtle effects of temperature change, possibly due to the effects of climate change.     

The strain energy function in axial plant growth

A model for axial plant growth is formulated based on conservation of energy. The model derivation assumes that a strain energy function exists to describe the dissipation of potential energy associated with water uptake, mechanical deformation, and biosynthesis during growth. The derivation does not, however, make any further assumption on the mathematical form of this constitutive relation. The model is employed to investigate possible forms of the strain energy function as applied to steady root growth. Solutions of the nonlinear partial differential equations governing growth are given for cases when the third derivative of the strain energy function is >, <, or =0. These three cases encompass a multitude of mathematical forms of the strain energy function. The resulting solutions are compared with the realization of steady axial root growth. The results of this analysis indicate that a quadratic form of the strain energy function best described steady growth. This conclusion is consistent with previous assumptions on the form of constitutive relations for growth, and allows further interpretation on the water relations, mechanical, and biosynthetic energies associated with plant growth.Research support provided by state and federal funds appropriated to the OSU/OARDC. Journal article no. 12–88     

Growth of the Brown Alga <Emphasis Type="Italic">Laminaria japonica</Emphasis> in a Laboratory Environment

The growth of an individual thallus of the brown alga Laminaria japonica was studied in a laboratory environment. It was found that daily accretion of the Laminaria thallus can remain constant for a long time. The blade grew in length at a distance from 0 to 15–25 cm from the stipe-blade border, which makes up 60% of the blade length. In width, the blade grew both in the central and in the lateral parts of the blade, 0 to 7–10 cm from the stipe-blade border, which makes up 30% of the frond length. The transposition of a perforation hole mark from the stipe-blade border toward the blade tip evidenced the formation of new tissue in the growth zone even when the thallus diminished in size due to destruction of the blade tip. Based on the results of this observation, it was concluded that both restraint of accumulation and even reduction of the algal thallus in biomass and size cannot be taken as an indication of algal growth cessation.Original Russian Text Copyright ¢ 2005 by Biologiya Morya, Skriptsova, Leletkin.     

Production of a biologically active novel goldfish growth hormone in Escherichia coli

Goldfish pituitary contains two types of growth hormones. One with five cysteine residues (type-I) similar to other Cyprinid GHs, and the other with four Cys residues (type-II) similar to those of other fish and tertapod species. Recombinant goldfish type II GH (gfGH-II) was produced in Escherichia coli using the pRSETB expression vector. The gfGH-II was produced fused to a leader sequence, which sequestered into inclusion bodies after expression. The inclusion bodies were solubilized using sodium hydroxide and the fusion protein purified by chelating affinity chromatography. Subsequently, gfGH-II was cleaved and analyzed by Western blotting, using a specific antiserum. For comparison we also produced recombinant common carp GH (cGH) which has 95% similarity to gfGH-II, and tested their growth promoting activity in goldfish. Both forms of GH significantly increased the growth rate of goldfish (P<0.05), although cGH was found to have a somewhat higher potency than gfGH-II.