实验性糖尿病大鼠胸腺的形态学研究

用四氧嘧啶诱导复制的大鼠实验性糖尿病动物模型，在光，电镜下，观察了糖尿病大鼠胸腺的形态学变化。结果表明：糖尿病大鼠胸皮质明显就薄，皮质淋巴细胞大量减少，细胞分裂盯计数显著降低。细胞退化。明上皮细胞呈明显的退行性变，其胞质内张力细丝束和溶酶体样致密颗粒明显增多，出现空泡化，自噬体及较多的含颗粒状物质的囊泡。     

实验性糖尿病大鼠胸腺的免疫组化研究

<正> 胰岛素依赖型糖尿病的发病与胸腺T细胞亚群分化异常有关,但对其在发病过程中的分化规律和作用机理尚未完全清楚.本实验给予SD大鼠一次性腹腔注射链脲佐菌素(STZ,65mg/kg)以诱导实验性糖尿病,做常规形态学及免疫组织化学染色观察实验性糖尿病状态下大鼠胸腺的形态结构、胸腺上皮细胞角蛋白(CK)表达及胸腺细胞表面CD4、CD8分子表达的变化.结果表明:本实验所诱导的实验性糖尿病大鼠均均出现典型的糖尿病症状,血糖值均在20.25mmol/L以上,远高于糖尿病大鼠的血糖标准值16.0mmol/L,说明本实验所用的建模方法效果较好.糖尿病大鼠胸腺发生病理性萎缩,CK8+的胸腺皮质上皮细胞相互联结构成的网中存在空洞状缺失,胸腺细胞表面的CD4、CD8表达呈区域状分布,主要分布于胸腺皮质部,髓质部较少见阳性反应细胞.结论:STZ诱导的实验性糖尿病大鼠伴有胸腺萎缩、胸腺皮质上皮缺失及胸腺细胞表面CD4、CD8的表     

绒毛膜促性腺激素对大鼠胸腺实质影响的形态学研究

应用光镜和电镜对绒毛膜促性腺激素(HCG)诱发幼年大鼠胸腺实质细胞的退化进行了观察.光镜观察发现:HCG引起胸腺皮质变薄.皮质淋巴细胞密度下降,细胞有丝分裂相数目显著减少.电镜下见胸腺上皮性网状细胞退行性变.明细胞变化尤为明显,细胞变性,空泡化、多数细胞器减少;一些细胞充满低电子密度的囊泡.淋巴细胞也呈退化现象.此外巨噬细胞增多,吞噬功能活跃.文中讨论了内分泌腺、性腺和胸腺的关系.     

放线菌酮诱导大鼠胸腺细胞凋亡的电镜观察

利用透射电镜详细观察了放线菌酮体内诱导大鼠腺细胞凋亡的形态学变化。观察显示，腹腔注射放线菌酮４小时后，大鼠胸腺细胞发生凋亡，凋亡胸腺细胞胞核和胞质发生一系列形态学变化，产生凋亡小体。主要表现为染色质断裂、浓缩、边集、大部分细胞核变成花瓣状，其它细胞核变成半月状、黑洞样和空泡状；粗面内质网大量增殖，并包裹细胞成分形成自噬体；线粒体增多，嵴紊乱并空泡化。凋亡细胞及其形成的凋亡小体被其它细胞吞噬清除。结     

绒毛膜促性腺激素对大鼠胞腺实质影响的形态学研究

应用光镜和电镜对绒毛膜促性腺激素（ＨＣＧ）诱发幼年大鼠胸腺实质细胞的退化进行了观察。光镜观察发现：ＨＣＧ引起胸腺皮质变薄，皮质淋巴细胞密度下降，细胞有些分裂相数目显著减少。电镜下见胸腺上皮性网状细胞退行性变，明细胞变化尤为明显，细胞变性，空泡化，多数细胞器减少；一些充满低电子密度的囊泡。淋巴细胞也呈退化现象。此外巨细胞增多，吞噬活跃。文中讨论了内分泌腺，性腺和胸腺的关系。     

大剂量雌二醇对大鼠胸腺的影响

本研究用大剂量苯甲酸雌二醇,诱导性成熟前SD大鼠的胸腺迅速退化,可见皮质明显变薄,皮、髓质比例降低,皮质内淋巴细胞大量减少。电镜下见胸腺的上皮性网状细胞(ERC)为一异质性细胞群,它们对雌二醇的反应性也各不相同。其典型的改变为:1.一部分明ERC呈明显的退行性变;2.另一部分明ERC内则充满低电子密度的囊泡;3.暗ERC明显增多,该细胞胞体及其突起的周围,都有许多胶原原纤维。血管周围间隙内也呈类似改变。淋巴细胞的超微结构虽未见异常,但胸腺内酸性非特异性酯酶(ANAE)阳性的T细胞数,明显低于对照组。胸腺皮质内有大量浆细胞聚集,其粗面内质网多高度扩张。本文在上述形态学观察基础上,就雌二醇诱导胸腺退化的机制进行了讨论。     

新生乳鼠胸腺的超微结构研究

本文研究新生乳鼠胸腺形态学特点,结果表明:1.胸腺小叶尚未完好形成,皮、髓质分界不甚清晰;2.髓质常可见由上皮细胞构成的囊性结构;3.内皮质有少数淋巴细胞胞浆含有糖原颗粒;4.胸腺小体少而小。本文描述了胸腺淋巴细胞、上皮性网状细胞、巨噬细胞、指突细胞等细胞成分和血胸屏障等结构的超微结构特征。     

Fabry病2例临床及病理特征分析

目的 探讨Fabry病的临床病理特征、诊断及鉴别诊断.方法 回顾性分析2例Fabry病患者的临床表现,并对其肾活检组织进行光镜、免疫荧光及超微结构观察,对皮肤活检组织进行常规病理学检查.结果 2例患者均出现蛋白尿、镜下血尿,皮肤黏膜出现散在出血点;光镜下见肾小球足细胞空泡变性,体积增大;肾小管上皮及间质亦出现泡沫样变;电镜下见肾小球足细胞体积增大,胞质内含大量具有嗜锇性髓鞘样包涵体,表现为髓样小体和斑马小体,足突部分融合,肾小球壁层上皮细胞、肾小管上皮细胞和间质可见上述现象.结论 Fabry病多见于青少年男性,常伴有肾外表现.肾小球足细胞内出现嗜锇性髓鞘样小体是Fabry病特征性的形态学改变,确诊需依靠电镜及测定血清α-半乳糖苷酶A（α-GalA）水平.     

新生儿胸腺的透射电镜观察

应用透射电镜观察了１１例人新生儿胸腺的超微结构，其中基本正常胸腺５例，萎缩胸腺６例。结果显示正常新生儿胸腺小叶已基本完成形成，皮、髓质分界清楚，胸腺外皮质区胸腺细胞分裂增殖旺盛；胸腺实质上皮细胞至少可分为四种类型，上皮细胞与胸腺细胞紧密直接接触，两者共生发育。萎缩胸腺见巨噬细胞吞噬大量坏死的胸腺细胞，重度萎缩胸腺基本结构紊乱，上皮细胞变性、崩解，上皮网架受损。     

胸腺小体在胸腺发育中的形态发生及其功能探讨

用组织化学与免疫组织化学技术对８例人胎的胸腺进行研究，观察在其发育过程中胸腺小体的形态变化有增殖细胞核抗原，花生凝集素和细胞角蛋白等的表达特征。结果显示：胸腺小体是在胸腺发育阶段由胸腺上皮细胞呈同心圆状排列而成，且胎儿胸中单个和融合状的胸腺小体部较成体胸明显增多。围成胸腺小体的上皮细胞从周边中央，角蛋白明显减少，增殖能力逐渐减弱，表现为逐渐退化的过程。证实胸腺小体是处理退变的上皮细胞的场所。另外，     

Electron microscopic study of involuting thymus of “lethargic” mutant mice

The thymus, which undergoes spontaneous involution three weeks after birth in “lethargic” mutant mice, was studied by electron microscopy. Ultrastructural alterations observed in the involuting thymus of “lethargic” mice resemble those of acute thymic involution induced by the administration of adrenal corticosteroids. The responsive cells in thymic involution of “lethargic” mice were cortical thymocytes, macrophages, and epithelial cells. The first indication of the involution was the appearance of a large number of degenerating thymocytes in the cortex. Pyknotic nuclei of degenerating thymocytes were observed within the macrophages. Macrophages of the involuting thymus were characterized by their content of thymocyte pyknotic nuclei as well as a variety of cytoplasmic inclusions. Cytoplasmic inclusions were also found in the epithelial cells. The inclusions were of two different types: (a) tonofibrils in markedly increased numbers in relation to a non-involuted thymus, and (b) large vacuoles with dense bodies and/or myelin figures, as found in a normal cell, but several times the number one would expect to find. A large number of lipid-laden cells were found in the involuted thymus. This type of cell was not seen in the normal thymus. Numerous Hassall's corpuscles were also found in the involuted thymus of “lethargic” mice.     

Ultrastructural study of the FVB/N mouse thymus: presence of an immature epithelial cell in the medulla and premature involution

FVB/N inbred mice have been widely used to generate a variety of transgenic lines, but their physiology and especially their immunological characteristics are poorly documented. We therefore studied the ultrastructure of the thymus and the distribution of thymocyte subpopulations in FVB/N mice at several ages. In young FVB/N mice the stromal microenvironment exhibits the three types of epithelial cells and the two types of bone-marrow derived cells (macrophages and interdigitated cells) previously described in other strains of mice. Moreover, in the thymic medulla of young FVB/N mice, a fourth cell type with the morphological characteristics of an immature epithelial cell was present in relatively high number. Furthermore, thymocyte subpopulations distribution shows an earlier thymocyte maturation than in other strains. Finally, changes associated with thymic involution were observed about 5 months earlier than in many other mouse strains. Our results demonstrated that the FVB/N strain has a specific immunological status.     

Apoptosis and the thymic microenvironment in murine lupus.

The thymus of New Zealand black (NZB) mice undergoes premature involution. In addition, cultured thymic epithelial cells from NZB mice undergo accelerated preprogrammed degeneration. NZB mice also have distinctive and well-defined abnormalities of thymic architecture involving stromal cells, defined by staining with monoclonal antibodies specific for the thymic microenvironment. We took advantage of these findings, as well as our large panel of monoclonal antibodies which recognize thymic stroma, to study the induction of apoptosis in the thymus of murine lupus and including changes of epithelial architecture. We studied NZB, MRL/lpr, BXSB/Yaa, C3H/gld mice and BALB/c and C57BL/6 as control mice. Apoptosis was studied both at basal levels and following induction with either dexamethasone or lipopolysaccharide (LPS). The apoptotic cells were primarily found in the thymic cortex, and the frequency of apoptosis in murine lupus was less than 20% of controls. Moreover, all strains of murine lupus had severe abnormalities of the cortical network. These changes were not accentuated by dexamethasone treatment in cultured thymocytes. However, the thymus in murine lupus was less susceptible to LPS-induced apoptosis than control mice. Finally we note that the number of thymic nurse cells (TNC) was lowest in NZB mice. Our findings demonstrate significant abnormalities in the induction of apoptosis and the formation of TNC-like epithelial cells in SLE mice, and suggest that the abnormalities of the thymic microenvironment have an important role in the pathogenesis of murine lupus.     

Cellular mechanism of thymic involution

Involution of the thymus and alterations in the development of thymocytes are the most prominent features of age-related immune senescence. We have carried out a comparative analysis of thymocyte and stroma in rapid thymic involution DBA/2 (D2) strain of mice compared with slow involution C57BL/6 (B6) strain of mice. Analysis of mice at 15 months of age suggested an age-related decrease in the thymocyte cell count, a block in the development of T cells and cortical involution in D2 mice compared with 3-month-old mice. TUNEL (terminal-deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling) staining and fluorescence-activated cell sorter (FACS) analysis showed that there was a significant increase in apoptotic cells in the cortex region of thymus in 15-month-old D2 mice compared with the same aged B6 mice. The thymocyte proliferation rate, as assessed by bromodeoxyuridine (BrdU) staining and [3H]-thymidine incorporation assay, was lower in 3-month-old D2 mice compared with the same age B6 mice. Immunohistochemical staining showed that the arrangement of MTS (mouse thymus stromal)-10+ epithelial cells and MTS-16+ connective tissue staining pattern had become disorganized in 15-month-old D2 mice but remained intact in B6 mice of the same age. These results suggest that, in D2 mice, both the thymocytes and stromal cells exhibit age-related defects, and that the genetic background of mice plays an important role in determining age-related alterations in thymic involution.     

The thymus in the mouse changes its activity during pregnancy: a study of the microenvironment

The mouse thymus changes dramatically during pregnancy. It shrinks in size, and the cortex is extensively reduced from midpregnancy onwards. Despite this, there is surprisingly little evidence for any increase in apoptosis, and considerable evidence that mitosis of thymocytes continues throughout pregnancy. In spite of overall involution the thymic medulla actually expands in midpregnancy due to a combination of mitosis of epithelial cells and an accumulation of lymphocytes. The extent and nature of these changes are examined in this study at the ultrastructural level. The epithelial cells of the subcapsular cortex (type 1 cells) become wrinkled and exhibit powers of phagocytosis, whilst the other cortical epithelial cells are relatively unchanged, although the formation of epithelial/thymocyte rosettes and thymic nurse cells is more clearly seen in midpregnancy than usual. Other changes associated with pregnancy involve the medullary epithelial cells that undergo an increased level of mitosis. Their greater numbers surround accumulations of lymphocytes to form the characteristic medullary epithelial rings. Cell movement through blood vessel walls was clearly observed in midpregnancy, but not at other times. Interdigitating cells in the medulla become more conspicuous as pregnancy proceeds and the cells become phagocytic. The endoplasmic reticulum in plasma cells becomes expanded, indicating increased secretory activity. These results highlight the active nature of the thymus in pregnancy in spite of its involution. This picture contradicts the conventional notion that an involuted thymus is inactive.     

Induction of Apoptosis and p53 Expression in Immature Thymocytes by Direct Interaction with Thymic Epithelial Cells

Apoptosis of normal thymocytes was shown to be triggered by several mechanisms (e.g. glucocorticoids, γ-irradiation). In the present study the authors report on thymocyte apoptosis that is induced by thymic epithelial cells. The thymocytes undergo a massive apoptotic death within 24 h of cocultivation with thymic epithelial cell monolayers derived from primary cultures (PTEC) or from a thymic epithelial cell line (TEC). Non-thymic monolayers were inactive. Apoptosis induction in this experimental model requires direct contact between the thymocytes and the thymic epithelial monolayer and can be blocked by anti-CD2 and anti-LFA-1 antibodies. The immature CD3^−/+dull CD4⁺CD8⁺ thymocytes were the cells which undergo apoptosis. The fact that the authors are dealing with a massive apoptotic process of immature cells in the absence of exogenous antigen suggests that it involves the nonselected thymocytes. The apoptotic pathway selected by thymocytes following their culturing on TEC involves p53 expression. Indeed it was found that TEC-induced apoptosis, led to the accumulation of p53 protein that preceded the step of DNA fragmentation in freshly isolated thymocytes as well as in a glucocorticoid resistant thymoma cell line. Since glucocorticoid-induced thymocyte apoptosis is p53-independent, glucocorticoids are conceivably not involved in TEC-induced thymocyte death. The in vitro experimental model presented here may reflect the physiological sequence of events leading to thymocyte death in the thymus.     

Effects of neonatal treatment with estrogens on the development of the thymus in rats

In order to study the effects of sex hormones administered during the neonatal period on the thymic development we have injected 5 days old female rats with a single dose (0.1mg) of estradiol benzoate. The evolution of the thymus gland after treatment was morphometrically analyzed. The thymus of the estrogen-injected animals diminished in size between the 7th and the 15th day, increasing afterwards. The cortex was the most sensitive compartment in the thymus to estrogenic treatment. Both thymic involution and enlargement were associated to changes in the frequency of large lymphoid cells in the subcapsular region and variations in the thymic cortex weights. The observed effects are tentatively attributed to alterations in the thymocyte differentiation probably due to modifications in the secretion of thymic hormones.