转化生长因子β1 mRNA在实验性肝癌间质差异形成中的意义

目的 :应用原位分子杂交技术观察TGF β1mRNA在实验性大鼠胆管细胞性肝癌 (CC)和肝细胞性肝癌 (HCC)中的表达 ,探讨肝癌间质差异形成的可能机制。方法 :大鼠肝癌组织经HE和AlcianBlue染色确认CC或HCC ,用TGF β1反义RNA探针检测TGF β1mRNA的表达 ,同时以TGF β1正链 ,β actin反义RNA探针分别作为阴性和阳性对照。结果 :CC中多数癌细胞内TGF β1mRNA有较强表达 ,HCC中仅少部分癌细胞胞浆内TGF β1mRNA呈弱到中等强度的表达 ;少数CC的间质细胞也有TGF β1mRNA表达。结论 :由于TGF β1是促进间质形成的重要因子 ,因此CC癌细胞及间质细胞合成并分泌的TGF β1可能是CC间质多于HCC间质的原因     

转化生长因子β(TGF-β)在实验性动脉粥样硬化发生中的作用

目的：研究TGF－β与动脉粥样硬化形成的关系。方法：用10％胆固醇脂肪乳剂复制大鼠和家兔的高脂血症模型,免疫组织化学和ELIA等技术检测其动脉和周围血的TGF－β1、β2、β3及其受体,观察比较两种动物动脉粥样硬化形成的情况和血清中的脂蛋白及总胆固醇水平。结果：实验组家兔100％形成动脉粥样斑,血清高密度脂蛋白在正常范围;实验组大鼠未见动脉粥样斑形成,但其血TGF－β和高密度脂蛋白随实验时间（鼠龄）的延长而升高。结论：ITGF－β可能在动脉内膜被高脂血症损伤后的炎性增生反应过程中起作用。     

快速实验性动脉粥样硬化模型的建立及相关分析

目的 建立快速实验性动脉粥样硬化模型.方法 40只雄性新西兰家兔,随机均分为二组:1)对照组:喂食普通颗粒兔饲料;2)AS模型组:喂食含胆固醇(1.5g/兔/天)颗粒兔饲料.分别于0周末、4周末和8周末记录家兔体重,同时采血测定血清总胆固醇(TC)和甘油三酯(TG)含量;并取若干兔的主动脉制作大体和显微标本,观察病变进展情况.结果 4周末,家兔高脂血症迅速形成:AS斑块出现,且斑块形成率为100%,至8周末,病变程度明显加重.其血脂改变及病变特点与文献报道的模型相比基本相似,但造模时间缩短.并且所用剂量胆固醇末对家兔的一般情况及体重带来明显的不良影响.结论 此模型是成功的.     

转化生长因子β1及其2型受体在实验性大鼠升主动脉瘤中的表达

目的 研究转化生长因子β1(TGFβ1)及其2型受体(TGFβRⅡ)在实验性大鼠升主动脉瘤中的表达及其意义. 方法 缩窄幼年Wistar大鼠升主动脉制作升主动脉瘤模型,4个月后处死动物,用免疫组织化学和Western blotting方法 检测动脉瘤壁TGFβ1和TGFβRⅡ的表达. 结果 免疫组织化学显示,TGFβ1表达于动脉瘤和对照组动脉全层;TGFβRⅡ大量表达于动脉瘤增生的内膜和中膜平滑肌层,而对照组表达很弱.Western blotting显示,动脉瘤组织中TGFβ1和TGFβRⅡ表达均强于对照组. 结论 TGFβ1和TGFβRⅡ在动脉瘤中表达强于对照组,TGFβ信号通路可能在动脉瘤形成过程中起重要作用.     

家兔实验性动脉粥样硬化血管重塑的形态定量分析

目的 :探讨AS血管重塑的几何形态变化规律。方法 :将 40只新西兰雄性家兔随机等分为正常对照组 (C组 )和动脉粥样硬化模型组 (AS组 ) ,分别于实验的第 4、8、12周末取各组家兔的胸主动脉进行定性观察及定量分析。结果 :随时间延长 ,AS组斑块面积逐渐增大 ,斑块检出率逐渐增加。管腔面积在早期斑块形成时并无改变 ,晚期则明显缩小。斑块面积及管腔面积均分别与内弹性膜包围面积 (IELA)、外弹性膜包围面积 (EELA)呈正相关关系 (P <0 .0 5 ) ,IELA和EELA间也呈显著正相关关系 (P <0 .0 1) ,但斑块面积与管腔面积间并无直线相关关系 (P >0 .0 5 )。结论 :家兔AS病变随时间延长逐渐加重 ,且在斑块形成时伴内弹性膜和外弹性膜的同时扩张 ,管腔狭窄与否主要与IELA和EELA相关。IELA和EELA可作为判断管腔狭窄及评价血管重塑的指标。     

实验性家兔动脉粥样硬化血管外器官的病理学变化

对50办家兔实验性动脉粥样硬化的血管及血管以外心、肝、脾、肺、肾等脏器,进行了系统的病理形态学观察,试图探讨动脉粥样硬化形成过程中高脂血症对内脏器官的影响。结果表明,高脂血症不仅可以诱发家兔动脉粥样硬化,也可使受试动物产生肺炎,肝细胞广泛脂变和水变,以及全身单核巨噬细胞系统反应。并着重讨论了内脏器官病变的发病机理。     

大鼠与家兔内脏共振频率对比研究

目的 研究低频振动条件下大鼠和家兔肠、肺、肾、胃、心、肝的共振频率和振动特点,为生物体器官共振损伤及其反应研究奠定基础.方法 SD大鼠和家兔各8只,1.5％戊巴比妥钠麻醉后,将加速度传感器固定于脏器表面.大鼠以仰卧位固定在用橡皮绳水平悬挂的胶合板上,从下往上锤击板底部,测量分析频谱响应,其最大值对应的频率即为共振频率；...     

实验性肺纤维化大鼠组织整合素α5β1和转化生长因子—β的表达

目的 研究纤维连接蛋白受体整合蛋白受体整合素α５β１在大鼠肺纤维化中的作用。方法 用免疫组化方法观察实验性大鼠肺纤维化纤维连接蛋白及其受体整合素α５β１和转化生长因子－β表达的动态变化：用Ｎｏｒｔｈｅｍ印迹杂交和免疫细胞化学方法观察ＴＧＦ－β对体外培养的大鼠肺成纤维细胞整合素α５β１ ｍＲＮＡ和 白表达的影响。结果 （１）实验组１￣３天,病灶内上皮细胞和骨皮细胞整合素α５β１表达明显增强,炎细胞及     

干扰素γ对实验性大鼠肺纤维化、肺组织干扰素γ和转化生长因子β表达的影响

目的：研究干扰素γ（IFN-γ）对博莱霉素诱导的大鼠肺纤维化实验模型肺泡炎和肺纤维化的影响,并探讨其对肺纤维化影响的可能机制。方法：60只SD大鼠随机分为正常对照组（N组）、模型对照组（M组）和干扰素γ组（R组）,每组各20只大鼠。于造模后3、7、14、28天分批处死动物,留取肺组织,观察肺泡炎和肺纤维化的程度,测定肺组织中的羟脯氨酸含量、IFN-γmRNA、转化生长因子β（TGF-β）mRNA的表达。结果：M组、R组大鼠肺泡炎3、7、14、28天均较N组严重,7天时最重,R组14天时肺泡炎显著高于M组;M组、R组肺纤维化评分及肺羟脯氨酸含量14、28天均高于N组,于28天最重;R组肺组织IFN-γmRNA表达3、7、14、28天均显著高于M组;R组肺组织中TGF-βmRNA表达在3天显著高于M组（P〈0.05）。结论：在博莱霉素诱导大鼠肺纤维化早期给予干扰素γ并不能减轻肺部炎症和肺纤维化,可能与其促进肺组织IFN-γ、TGF-β基因表达有关。     

Localisation of neuronal nitric oxide synthase-immunoreactivity in rat and rabbit retinas

The distribution of neuronal nitric oxide synthase (NOS) immunoreactivity was examined in rat and rabbit retinas and was compared with the distribution of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactivity and vasoactive intestinal peptide (VIP) immunoreactivity. An antibody raised against a C-terminal fragment of a cloned rat cerebellar NOS was used to localise NOS immunoreactivity. NOS immunoreactive cells were not detected in rat retinas at postnatal day 1 or 4, but were seen from postnatal day 7 onwards. NOS immunolabelling was seen in a small population of cells in the proximal inner nuclear layer. Most of the labelled cells had the position of amacrine cells and were seen to send processes into the inner plexiform layer. A few labelled cells were at times also seen in the ganglion cell layer, which are likely to correspond to displaced amacrine cells. The same NOS-labelling pattern was seen in rat and rabbit retinas.NADPH-diaphorase staining was observed in both species, in photoreceptor inner segments, in cells with the position of horizontal cells, in a subset of amacrine and displaced amacrine cells, in large cell bodies in the ganglion cell layer, in both plexiform layers, and in endothelium. Colocalisation of NOS immunoreactivity and NADPH-diaphorase staining was only observed among amacrine cells. However, not all NADPH-diaphorase-reactive amacrine cells were found to be NOS immunoreactive. VIP immunoreactivity was also localised in rat retinas in a subpopulation of amacrine cells, but no colocalisation of NOS and VIP immunoreactivity was observed.Our observations indicate that only amacrine cells contain the NOS form recognisable by the antibody used, and suggest that different isoforms of neuronal NOS may be present in retinal cells. Further, the onset of NOS expression in rat amacrine cells appears to occur independently of neuronal activity.Paper in honour of Professor Rolf Elofsson on the occasion of his retirement from the chair of Zoology at the University of Lund     

内皮脂酶在动脉粥样硬化及冠心病中的研究进展

内皮脂酶(endothelial lipase,EL)是近年来发现的三酰甘油脂肪酶基因家族的新成员,它是HDL代谢的关键酶。EL通过降解HDL而在冠心病发病过程中起着重要作用。近年来的基础研究发现:EL参与了脂质代谢、内皮损伤、炎症反应这三个动脉粥样硬化(atherosclerosis,AS)形成的关键过程,因此EL可能是AS形成的枢纽及媒介。临床研究也表明EL可能是冠心病的重要危险因素。但目前EL与冠心病关系的研究多为基础研究,临床研究尚刚刚起步。     

大鼠及家兔脑动脉的比较及其在脑缺血模型中的应用

目的　观察和比较大鼠、家兔脑动脉的形态特点。方法　利用墨汁、乳胶混合液灌注的 45只鼠和 5 0只兔脑标本 ,在光镜下观察脑动脉的起始、行程和分布。结果　大鼠和家兔的椎 基底动脉系血管起始、行程基本相同。大鼠的脑底动脉环闭锁型的出现率是 97 78% ,组成环的两侧血管等粗 ,对称者是 80 0 0 %。而家兔脑底动脉环闭锁型出现率是 80 0 0 % ,环两侧血管对称者占 2 8 0 0 %。大鼠的大脑中动脉均是 1枝型 ,起始、行程恒定。兔的大脑中动脉 1～ 2枝不等 ,行程短 ,其分布范围内尚有 1～ 2枝梨状区动脉存在。结论　与家兔相比 ,大鼠的脑动脉更接近人类 ,是制做脑缺血模型理想的实验动物。     

Cardioventilatory coupling in the anaesthetised rabbit, rat and guinea-pig

 Cardioventilatory coupling is a temporal coherence of respiratory and cardiac rhythms, seen in humans at rest, and during sleep and anaesthesia. In this study we compared the cardioventilatory coupling of anaesthetised rabbits, rats and guinea-pigs. Breathing two successive anaesthetic concentrations (1 or 2% isoflurane) we compared the effect of anaesthetic depth and species on (1) heart rate, (2) heart rate variability, (3) ventilatory rate (f), (4) ventilatory variability, (5) ratio HR/f, (6) degree of coupling (Shannon entropy of the distribution of intervals between inspiration and the preceding electrocardiographic R wave – the RI interval) and (7) coupling pattern, classified into four sub-patterns (I-IV) based upon inspection of the RI interval time series. Rabbits exhibited significantly less ventilatory variability and coupling than rats or guinea-pigs. The sub-pattern of coupling also differed between the three species. Rabbits showed coupling only when HR and f were close to integer ratios whereas other species coupled at non-integer ratios. Ventilatory variability in the rat and guinea-pig differed according to the pattern of coupling observed. Of the three species studied, the rat and guinea-pig demonstrated coupling most similar to that of anaesthetised human subjects. Anaesthetic concentration did not influence the pattern or degree of coupling. Received: 28 July 1998 / Received after revision: 24 November 1998 / Accepted: 8 January 1999     

胰岛素样生长因子结合蛋白2、4在实验性肝细胞损伤中的表达及意义

目的：通过观察肿瘤坏死因子α (TNF -α)和转化生长因子β1（TGF-β1）两种细胞因子所致体外培养的肝细胞损伤时胰岛素样生长因子结合蛋白2、4(IGFBP2、IGFBP4)的表达变化,探讨IGFBP2和IGFBP4在肝损伤中的作用机制。方法：对人肝细胞株HL-7702分别给予不同浓度的TNF-α、TGF-β1两种处理因素作用24 h,采用免疫细胞化学染色法观察其IGFBP2和IGFBP4的表达变化,再在相同处理培养条件下用MTT比色法检测两种细胞因子对肝细胞抑制率的影响。根据MTT及预实验结果选择TNF-α 20 μg/L作用于人肝细胞株48h,采用Annexin-Ⅴ/PI双染色流式细胞分析法和TUNEL法检测肝细胞凋亡发生率。结果：与对照组相比,各处理组IGFBP2、IGFBP4的表达均显著增加(P<0.05),其中在TNF-α 20 μg/L组和TGF-β1 4 μg/L组表达最强,且与肝细胞抑制率呈正相关关系(P<0.05 or P<0.01)。TNF-α 20 μg/L处理48 h后肝细胞凋亡率明显增加(P<0.01)。结论：IGFBP2、IGFBP4参与了肝细胞的损伤过程,在TNF-α、TGF-β1介导的肝细胞损伤中具有重要作用。     

NOS-like immunoreactive neurons express GABA-like immunoreactivity in rabbit and rat retinae

In rabbit and rat retinae, wholemounted preparations and 40 μm thick vibratome sections were processed for nitric oxide synthase (NOS) immunoreactivity and consecutive semithin sections were immunostained with anti-NOS and anti-GABA antisera, respectively. Two types of NOS-labelled amacrine cells were identified: type 1 cells with larger somata were intensely stained, and type 2 cells with smaller somata were weakly stained. A few displaced amacrine cells also showed NOS-like immunoreactivity. All these NOS-like immunoreactive neurons also expressed GABA-like immunoreactivity. Thus, nitric-oxide-containing neurons might constitute a subpopulation of GABAergic neurons in rabbit and rat retinae. Received: 18 August 1997 / Accepted: 15 October 1997     

Acquired thymic tolerance and experimental allergic encephalomyelitis in the rat. I. Parameters and analysis of possible mechanisms

Intrathymic injection of guinea pig myelin basic protein (MBP) or the immunodominant, ence phalitogenic fragment of MPB, 68 – 86, without otherwise compromising the peripheral lymphocyte pool in adult LEW rats, dramatically inhibits onset of experimental allergic encephalomyelitis (EAE) caused by the usual peripheral inoculation with MBP in complete Freund's adjuvant. This surprising finding demonstrates that interaction of antigen and one or more components of an intact thymus can down-regulate systemic responses by mature T cells already existing in the peripheral lymphocyte pool. How this happens is not known. In studies designed to explore possible mechanisms: (a) adult thymectomized animals remain susceptible to active EAE, thus EAE cannot be attributed solely to recent thymic emigrants that might be inactivated by antigen deposited in the thymus; (b) heterotopic isografts of injected thymic lobes transfer thymic tolerance to secondary recipients, thus the tolerance effect is dominant over an intact, non-treated thymus; (c) T cells from made thymic tolerant but not immunized donors are less effective in causing EAE following adoptive transfer into, and active immunization of, secondary, irradiated recipients; and (d) animals resistant to active EAE as a consequence of thymic tolerance are fully vulnerable to adoptive EAE caused by already activated MBP-specific T cell subpopulations. These results rule out a possible mechanism previously proposed for acquired thymic tolerance, i. e., that potentially pathogenic T cells traffic to the antigen-injected thymus where they are inactivated or eliminated.     

肺纤维化大鼠中基质金属蛋白酶-2的表达

目的：研究基质金属蛋白酶－2（MMP2）在肺纤维化中的作用。方法：（1）用免疫组织化学方法（ABC法）观察博莱霉素所诱导的实验性大鼠纤维化肺组织内MMP2表达的动态变化;（2）用逆转录－聚合酶链反应（RT－PCR）观察博莱霉素所诱导的肺纤维化不同时期间质成纤维细胞MMP2 mRNA的动态变化。（3）用Northern印迹杂交和免疫细胞化学方法观察转化生长因子β1（TGFβ1）对体外培养的大鼠肺成纤维细胞MMP2mRNA和蛋白表达的影响。结果：（1）诱导纤维化组1－7d,病灶内浸润的单核巨噬细胞及肺泡间质细胞数量增多,MMP2免疫组织化学染色阳性,14d以后,阳性单核巨噬细胞减少,用博莱霉素28d时,阳性间质细胞亦减少。（2）博莱霉素作用后1d,肺成纤维细胞MMP2基因转录即明显增强,为对照组的2．05倍,28d时下降。（3）TGFβ1作用后,大鼠肺成纤维细胞MMP2mRNA及其蛋白表达增强。结论：肺组织内MMP2的过度表达,可能是肺纤维化启动的重要原因。     

大鼠视上核、室旁核肠三叶因子表达与实验性胃溃疡的关系

目的探讨大鼠实验性胃溃疡自愈期间肠三叶因子(ITF)在下丘脑视上核(SON)、室旁核(PVN)的表达及其与实验性胃溃疡愈合的关系。方法以免疫组织化学染色、酶联免疫吸附实验分别检测溃疡组(42只)和正常组(6只)大鼠下丘脑和血清及ITF的表达及含量变化,RT-PCR检测ITFmRNA的转录情况。结果 ITF免疫反应阳性物质主要位于视上核和室旁核大细胞部。溃疡1d视上核和室旁核ITF积分吸光度略增高,2d、4d和6d逐渐升高,6d达高峰(P0.01),10～23d均维持在较高水平(P0.05)。血清ITF的变化与免疫组织化学法结果相似;溃疡组ITF/3-磷酸甘油醛脱氢酶(GAPDH)吸光度比值在溃疡2～23d均高于正常组(P0.01,或P0.05)。结论胃溃疡自愈期间可能通过下丘脑和血清ITF的高表达参与溃疡愈合的调节。