淋巴组织内的性激素受体

性激素包括雌激素(estrogen,E)、雄激素(androgen,A)和孕激素(progesterone,P),它们在免疫调节中具有重要作用。A和E都可诱使胸腺和外周淋巴器官萎缩,相反,雌、雄性腺切除能引起淋巴组织肥厚。性激素的免疫调节作用是否通过其相应的特异性受体介导的?此问题促使人们在淋巴组织内寻找性激素受体(sex hormone receptor,SHR)。目前已在大鼠、小鼠、豚鼠、鸡及人类的淋巴组织内发现SHR,研究最多的是大鼠胸腺。现就淋巴组织内的SHR有关方面作一简述。     

性激素对抗体分泌细胞表面分子表达和抗体分泌的影响

目的：探讨性激素调控抗体分泌细胞游走到生殖道的分子机制和对局部抗体分泌的影响。方法：以鼠源杂交瘤细胞SG2和PA4为对象，检测其性激素受体、CXCR4的mRNA和CD31的表达；用流式细胞术和ELISA检测不同浓度性激素作用下，抗体分泌细胞表面与细胞游走相关分子的表达和抗体分泌的变化。结果：SG2和PA4细胞表达雄激素受体和雌激素受体β，表达CXCR4，但不表达CD31。性激素对抗体分泌细胞表面分子的表达和抗体分泌量并没有明显的影响。结论：性激素对抗体分泌细胞游走的调控作用与细胞自身相关黏附分子的变化关系不大，推测可能主要是通过对内皮细胞地址素表达的影响来实现的。     

人类卵巢淋巴孔的发现及其意义

目的　研究人类卵巢淋巴孔的超微结构 ,并与动物卵巢或卵巢囊淋巴孔比较以探讨其功能。　方法取手术切除的新鲜卵巢组织 ,进行常规和NaOH消化扫描电镜观察 ,应用Elescope计算机图像处理软件对人类卵巢淋巴孔作定量处理。　结果　在扫描电镜下 ,人类卵巢上皮细胞可区分为扁平细胞和立方细胞。在立方细胞间、立方和扁平细胞之间有成簇或散在分布的淋巴孔 ,其直径 1 80± 0 82 μm ,周长 6 2 7± 2 6 5 μm。同时发现卵巢囊腺瘤瘤壁外表面也存在淋巴孔。　结论　人类正常卵巢上皮细胞之间 ,以及卵巢囊腺瘤瘤壁外表面都存在卵巢淋巴孔 ,藉卵巢淋巴孔使卵巢内淋巴管与腹膜腔相沟通 ,并为解释卵巢肿瘤早期腹腔转移提供了形态学依据     

金仓鼠卵巢囊及卵巢囊淋巴孔的研究进展

卵巢系膜（ｍｅｓｏｔｕｂａｒｉｕｍ　ｓｕｐｅｒｉｕｓ,　ＭＴＳ）的发展程度有很大的种属差异。大多数啮齿类的卵巢系膜高度发展形成一个（几乎）完全闭口、包裹卵巢的囊,这个囊称卵巢囊（ｏｖａｒｙ　ｂｕｒｓａ）。淋巴孔是毛细淋巴管在间皮面的微小开口。金仓鼠的卵巢囊围绕卵巢形成完全的包裹,并且其内壁存在卵巢囊淋巴孔。本文综述了金仓鼠卵巢囊的形态结构、出生后卵巢囊及囊腔的发育以及卵巢囊淋巴孔的形态、功能,囊腔内液的引流等研究结果。     

雌激素缺乏状态下牙周组织中核转录因子κB及白细胞介素17的表达变化北大核心

背景:绝经期后骨质疏松症与牙周组织疾病有着十分密切的关系,而其作用机制尚不清楚。目的:通过切除卵巢建立雌激素缺乏状态下骨质疏松小鼠模型,观察在此状态下牙槽骨组织中核转录因子κB以及血清与牙龈组织中白细胞介素17的表达变化。方法:将3月龄雌性C3H小鼠随机分为卵巢切除组及假手术组。术后10周,苏木精-伊红染色观察下颌骨及股骨组织学改变;RT-PCR检测下颌骨中成骨相关因子OCN及Runx2表达变化;免疫组化染色及Western Blot检测下颌骨中核转录因子κB表达;CBA流式液相多重蛋白定量技术检测血清及牙龈组织匀浆中白细胞介素17水平。结果与结论:(1)卵巢切除组小鼠股骨的骨皮质变薄,骨髓腔扩大,骨小梁变细、数目减少、密度降低、结构不完整,骨吸收陷窝样结构增多;(2)卵巢切除组牙槽骨组织中OCN及Runx2相对表达量较假手术组低;(3)卵巢切除组小鼠下颌骨中核转录因子κB活化形式P65蛋白呈阳性表达;(4)卵巢切除组牙槽骨组织中核转录因子κB活化形式P65相对表达量高于假手术组;(5)卵巢切除组小鼠血清中白细胞介素17表达水平高于假手术组,但牙龈组织中白细胞介素17表达水平与假手术组相比无明显变化;(6)实验表明,雌激素缺乏导致的核转录因子κB信号通路激活可能在牙周骨吸收中发挥一定作用;而牙周局部组织内的白细胞介素17可能并非此状态下牙周组织破坏的关键因子。     

性激素雌激素受体与红斑狼疮的免疫失调

性激素(特别是雌激素)与SLE 密切相关,它可通过与胸腺、免疫活性细胞、中枢神经系统及骨髓中的雌激素受体结合,导致胸腺素产生减少、Ts 细胞活性受抑制、免疫复合物清除降低。雄激素则通过减少雌激素受体维持Ts 细胞活性、增加免疫复合物的清除。故应用雄激素制剂和雌激素拮抗剂治疗SLE,可望缓解。     

NO对小鼠腹膜淋巴孔的调控作用与腹膜透析失超滤机理研究

目的:研究一氧化氮(NO)对腹膜淋巴孔的调控作用, 探讨腹膜透析(PD)失超滤机理。方法:①应用Baxter腹透液建立腹膜透析小鼠模型;②小鼠腹腔注射NO供体硝普钠(SNP)和NOS的抑制剂N^G-单甲基-L-精氨酸(L-NMMA);③全自动酶标仪测定血清NO₂^-量;④腹膜淋巴孔的扫描电镜观察和计算机图像处理。结果:①随着腹膜透析进行, 大量巨噬细胞经腹膜淋巴孔游出, 进入腹膜腔形成乳斑;血清NO₂^-量逐渐增高, 腹膜淋巴孔孔径增大、分布密度增高。停止腹膜透析、乳斑减少, NO₂^-量逐渐降低, 腹膜淋巴孔渐趋正常。②随SNP剂量增加, 小鼠血中NO₂^-浓度显著提高, 淋巴孔的直径和密度明显增加。③随着L-NMMA剂量增加, 小鼠血中NO₂^-浓度明显降低, 腹膜淋巴孔开放数量减少, 淋巴孔密度降低, 淋巴孔孔径变小。结论:NO有调控腹膜淋巴孔的作用;长期腹膜透析使血清NO₂^-浓度逐渐增高, 高浓度NO₂^-可舒张腹膜淋巴孔, 使腹膜淋巴孔对腹透液吸收增加, 导致腹膜透析失超滤。     

血管紧张素Ⅱ对心包积液淋巴转归的实验研究

目的:观察血管紧张素Ⅱ(ANGⅡ)对蛙心包淋巴孔、心包间皮的作用,研究其对心包淋巴孔的调控和间皮通透性的影响,探讨心包积液淋巴转归途径。方法:经蛙腹膜腔注射ANGⅡ,扫描电镜观察,计算机图象处理。结果:心包淋巴孔为环状开口,ANGⅡ组淋巴孔的平均直径为1.81μm,显著大于正常对照组0.73μm(P<0.05);ANGⅡ组淋巴孔的分布密度为12.74个/0/1mm~2,也显著大于正常对照组3.59个/0.1mm~2(P<0.01);经计算机图象处理,ANGⅡ组心包壁层间皮血窦状结构的面积为2140.76μm~2/0.1mm~2,明显多于正常对照组的986.18μm~2/0.1mm~2(P<0.01)。结论:ANGⅡ可使淋巴孔开放数目增多,孔径增大,分布密度增高,对心包淋巴孔有显著调控作用,并可增加心包间皮通透性,加速心包腔内物质转归,提示心包的淋巴引流作用与心包积液(生理)的产生和心包积液(病理)的吸收有关。     

二参泽术汤对腹膜淋巴孔的影响及腹水转归机理的研究

目的:研究二参泽术汤对腹膜淋巴孔的调控作用和治疗腹水的意义,并应用NO供体 (硝普钠)和一氧化氮合酶 (NOS)抑制剂 (N^G-单甲基-L-精氨酸),观察NO的淋巴孔舒张作用和对腹水转归影响,探讨二参泽术汤对腹膜淋巴孔的调控机制。方法:应用CCl4 法建立小鼠肝纤维化模型;用扫描电镜观察,并使用计算机与扫描电镜联机的图像处理系统测定腹膜淋巴孔的变化;用全自动生化分析仪测定尿离子浓度。结果:①二参泽术汤可明显促进腹膜淋巴孔开放面积增大,周长和分布密度增加 (P <0.01),尿中Na⁺ 、K⁺ 、Cl^-排出增多 (P <0.05或P <0.01);②二参泽术汤对腹膜淋巴孔的调控和对腹水转归的作用可以被NO供体和NOS抑制剂增强或抑制。结论:①二参泽术汤能调控腹膜淋巴孔,促进腹膜腔内液体转归,使尿中Na⁺ 、K⁺ 、Cl^-排出增加,减轻水钠潴留,具有良好的消腹水作用;②二参泽术汤调控腹膜淋巴孔,促腹水转归机制,可能与内源性NO的变化存在着密切的关系.     

雌激素刺激活动性狼疮肾炎外周血单个核细胞的IL-10表达

探讨性激素对活动性狼疮肾炎外周血单个核细胞 (PBMC)Th2细胞活化的影响。采用ELISA、RT PCR等方法检测了雌激素对 19例活动性狼疮肾炎和 16例健康人外周血单个核细胞 (PBMC)IL 10表达的调节作用。活动期狼疮肾炎PBMCIL 10mRNA和蛋白含量明显高于正常人 (P <0 0 5 ) ;与正常对照相比 ,雌激素明显提高了活动性狼疮肾炎PBMCIL 10蛋白和mRNA水平 (P <0 0 5 ) ,雄激素的加入明显抑制了雌激素诱导的活动性狼疮肾炎PBMCIL 10蛋白和mRNA水平 (P <0 0 5 )。雌激素、雄激素比例失调可能参与了活动性狼疮肾炎IL 10的高效表达     

Ultrastructure and Estrogen Regulation of the Lymphatic Stomata of Ovarian Bursa in Mice

The ovarian bursa is a key player in maintaining adaptive ovarian microenvironment for ovulation. The lymphatic stomata are believed to be a major contributor to execute the function of the ovarian bursa, whereas little is known about their ultrastructure and regulation. Here, we examined the ultrastructure of lymphatic stomata in mouse ovarian bursa by scanning electron microscopy and transmission electron microscopy and investigated its regulation by estrogen. We found that the mesothelium on the visceral layer of mouse ovarian bursa was composed of the cuboidal and flattened cells. The lymphatic stomata with round and oval shapes were mainly among the cuboidal cells. The particles, cells, and fluid passed through the stomata and entered into the lymphatic drainage unit composed of connective tissue and lymphatic endothelial cells beneath the stomata. We also used trypan blue as a tracer and found that the absorption of trypan blue through the lymphatic stomata was increased by estrogen that enlarged the average opening area of lymphatic stomata. Furthermore, we detected that there existed estrogen receptors in the nuclei of the mesothelial cells on the visceral ovarian bursa by using immunoelectron microscopy. Taken together, these data suggest that both the absorption and opening area of the lymphatic stomata in mouse ovarian bursa may be influenced by estrogen. Anat Rec, 290:1195‐1202, © 2007 Wiley‐Liss, Inc.     

Ultrastructural study of pleural lymphatic drainage unit and effect of nitric oxide on the drainage capacity of pleural lymphatic stomata in the rat.

The objective of this study was twofold: first to investigate the ultrastructure of the lymphatic drainage unit on the costal pleura of rats by electron microscopy, and secondly to examine the effect of nitric oxide on the pleural lymphatic stomata and fluid absorption from the pleural cavity. The lymphatic drainage unit of the rat costal pleura is composed of three special components: the lymphatic stomata between the mesothelial cells, the initial part of the lymphatic vessels and the underlying connective tissue containing many foramina. The unit is the main passage to drainage fluid, particles and cells in the pleural space. To investigate the regulator of the lymph drainage, nitric oxide synthase inhibitor and nitric oxide donor were injected into the peritoneal cavity of the rats, respectively. Trypan blue was used as tracer. The ultrastructural changes of pleural lymphatic stomata were observed under scanning electron microscope and analyzed by a computer image processing system. It turned out that the area and density of the pleural lymphatic stomata were positively correlated with the nitric oxide quantity (p < 0.05). After the tracer was injected into the pleural cavity, the nitric oxide donor group exhibited a higher trypan blue concentration than the control group (p < 0.05). The ability of the pleura to absorb trypan blue was enhanced because of the larger opening of the lymphatic stomata (p < 0.05). It is suggested that nitric oxide can increase lymphatic absorption of the pleura by opening pleural lymphatic stomata.     

大鼠膈腹膜间皮孔的电镜观察

用扫描电镜和透射电镜观察了正常大鼠膈腹膜间皮，并观察了腹膜腔内注射中国墨汁和兔血液后大鼠膈腹膜间皮的变化以及腹膜腔和间皮下毛细淋巴管的关系。     

人体腹膜孔淋巴引流单位的超微结构研究

用电镜和锇酸－二甲基亚砜－锇酸（ＯｓＯ４－ＤＭＳＯ－ＯｓＯ４，ＯＤＯ）冷冻断裂技术观察了人体腹膜孔淋巴引流单位的超微结构，淋巴引流单位位于腹膜孔内，由３种结构组成，即立方形间皮细胞、淋巴陷窝内皮细胞和两者之间的结缔组织。上述３种结构相互并置，但其间无特殊的连接结构。立方形间皮细胞常伸出瓣膜状胞质突起，使腹膜下小管呈蜿蜓曲折状。间皮下结缔组织中成纤维细胞的胞质突起可与淋巴陷窝内皮细胞相贴，而结缔组织     

The presence of lymphatic stomata in the ovarian bursa of the golden hamster

The histology and function of the lymphatic system in the ovarian bursa of the golden hamster were examined at each day of the estrous cycle. The lymphatic passage from the ovarian bursa to a para-aortic lymph node was stained black by india ink injected into the bursal cavity. This suggests that bursal fluid drains from the cavity via lymphatic vessels. Lymphatic stomata connecting the bursal cavity with the lymphatic lumen were consistently present throughout the cycle. However, the stomata were more frequently observed in the bursae on day 1 than on day 4 of the cycle. Also, they were more frequently observed in the bursa injected with 5 microliters of chick erythrocytes than in the contralateral (not injected) bursa in hamsters on day 4 of the cycle. These results suggest that the stomata are openings the patency of which varies in response to changes in the bursal cavity. There were regions where the lymphatic lumen was separated from the bursal cavity only by lymphatic endothelial cells. These regions were present throughout the estrous cycle. They may be patent stomata; dehiscence of junctions between the endothelial cells may give rise to stomata or widen the stomata orifices that are already present.     

Scanning and transmission electron microscopic study of visceral and parietal peritoneal regions in the rat

The visceral peritoneum of intraabdominal organs (spleen, stomach, liver, small intestine), omentum majus and the parietal peritoneum of the anterior abdominal wall and the diaphragm were studied in adult Wistar rats by combined scanning and transmission electron microscopy (SEM, TEM). In general, the peritoneal surface consisted of a mesothelium composed of cubic, flat or intermediate cell types delimited by a basal lamina. Cubic mesothelial cells predominated in parenchymal organs (spleen, liver) and were characterized by prominent and indentated nuclei, a cytoplasm richly supplied with organelles, a dense microvillous coat, basal invaginations and elaborate intercellular contacts. Flat mesothelial cells were observed in the intestinal, omental and parietal peritoneum (tendinous diaphragm, abdominal wall) and showed elongated nuclei, scant cytoplasm, a poorly developed organelle apparatus and sparsely distributed microvilli. An intermediate mesothelial cell type was described within the gastric peritoneum characterized by a central cytoplasmic protrusion at the nuclear region containing most of the cytoplasmic organelles and by thin finger-like cytoplasmic processes. The submesothelial connective tissue layer was composed of collagen fiber bundles, fibroblasts and free cells (macrophages, granulocytes, mast cells) and contained blood and lymphatic vessels. In the spleen, elastic fibers formed a membranous structure with intercalated smooth muscle cells. Mesothelial openings were observed as tunnel-like invaginations within the hepatic peritoneum and as clusters of peritoneal stomata within the parietal peritoneum of the anterior abdominal wall and the muscular diaphragm. The round or oval openings of the peritoneal stomata were frequently occluded by overlapping adjacent mesothelial cells and their microvillous coat or obstructed by cellular material. At the side of the peritoneal stomata the mesothelial cell layer was interrupted to allow a direct access to the underlying submesothelial lymphatic system. The mesothelium and lymphatic endothelium shared a common basal lamina. The endothelial cells were discontinuous and displayed valve-like plasmalemmatic interdigitations facilitating an intercellular transport of fluids and corpuscular elements from the peritoneal cavity to the submesothelial lymphatic lacunae. The findings underline the morphological heterogeneity of the peritoneum in visceral and parietal regions, suggesting different functional implications, and further support the presence of extra-diaphragmatic peritoneal stomata.     

On the presence and function of closed lymphatic stomata in the diaphragm of the golden hamster

The peritoneal surface of the golden hamster diaphragm was examined for closed lymphatic stomata by scanning electron microscopy (SEM) and serial sectioning. Closed stomata were absent on SEM but present on serial sectioning. Some closed stomata in the serial sections were reconstructed using a computerized image analysis system. They were less than 10 microns in diameter and consisted of an outer mesothelial margin and an inner lymphatic wall. The lymphatic wall was formed by several endothelial cells adjoined with various junctional abutments. The discrepancy of results between SEM and serial sectioning, and the functional aspects of lymphatic stomata are discussed.     

Acute injury and regeneration of the mesothelium in response to asbestos fibers.

The mesothelium is a target of the toxic and carcinogenic effects of asbestos fibers. Fibers greater than 8 mu in length and less than 0.25 mu in diameter have been found to be highly tumorigenic in rodents, while shorter asbestos fibers or spherical mineral particles have not been shown to produce mesotheliomas. For investigation of early mesothelial reactions associated with the development of mesotheliomas, C57BL/6 mice were given intraperitoneal injections of 200 micrograms of short or long crocidolite asbestos fibers, toxic silica particles, or nontoxic titanium dioxide particles. At intervals between 3 hours and 21 days after a single injection, the mesothelial surface of the diaphragm was examined by stereomicroscopy, scanning electron microscopy, and autoradiography. Within 6 hours after injection of asbestos fibers, mesothelial cells in the lacunar regions of the diaphragm retracted opening stomata 10.7 +/- 2.3 mu in diameter leading to the submesothelial lymphatic plexus. Short asbestos fibers (90.6% less than or equal to 2 mu in length), silica, or titanium dioxide particles (less than or equal to 5 mu in diameter) were cleared through these stomata without provoking an inflammatory reaction or mesothelial injury. In contrast, long asbestos fibers (60.3% greater than or equal to 2 mu in length) were trapped at the lymphatic stomata in the lacunar regions on the peritoneal surface of the diaphragm. At these sites, an intense inflammatory reaction developed with accumulation of activated macrophages and a 5.5-fold increase in albumin recovered in the peritoneal lavage fluid after 3 days. As early as 12 hours after injection of long asbestos fibers, the adjacent mesothelial cells were unable to exclude trypan blue and lost their surface microvilli, developed blebs, and detached. Recovery of lactate dehydrogenase activity in the peritoneal lavage fluid was increased 5.8-fold after 3 days and returned to normal levels after 14 days. Regenerating mesothelial cells appeared at the periphery of asbestos fiber clusters 3 days after injection. Maximal incorporation of 3H-thymidine by mesothelial cells occurred after 7 days, followed by partial restoration of the mesothelial lining after 14-21 days. As late as 6 months after a single injection of crocidolite asbestos fibers, clusters of fibers remained in the lacunar regions, partially covered by mesothelium but surrounded by macrophages and regenerating mesothelial cells. The anatomic distribution and size of lymphatic stomata on the peritoneal surface of the diaphragm account for the selective accumulation of long asbestos fibers in these regions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Recent Advances in the Research of Lymphatic Stomata

Lymphatic stomata are small openings of lymphatic capillaries on the free surface of the mesothelium. The peritoneal cavity, pleural cavity, and pericardial cavity are connected with lymphatic system via these small openings, which have the function of active absorption. The ultrastructure of the lymphatic stomata and their absorption from the body cavities are important clinically, such as ascites elimination, neoplasm metastasis, and inflammatory reaction. The lymphatic stomata play an important role in the physiological and pathological conditions. Our previous study indicated for the first time that nitric oxide (NO) could regulate the opening and absorption of the lymphatic stomata. It could decrease the level of free intracellular calcium [Ca²⁺] through increasing the cyclic guanosine monophosphate (cGMP) level in the rat peritoneal mesothelial cells, thus regulating the lymphatic stomata. This process is related with the NO‐cGMP‐[Ca²⁺] signal pathway. In this review, we summarize the recent advances in understanding the development and the function of the lymphatic stomata. The ultrastructure and regulations of the lymphatic stomata are also discussed in this review. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.     

Development of the peritoneal lymphatic stomata and lymphatic vessels of the diaphragm in mice

The generation and development of the peritoneal lymphatic stomata (PLS) and lymphatic vessels of the diaphragm were studied in mice at gestational ages from the embryonic to the postnatal period with TEM, SEM and enzyme histochemistry and the PLS data were quantitatively analyzed with computer-assisted image processing technology (Elescope image analysis software). The results showed that the diaphragmatic mesothelium was covered only by flattened mesothelial cells (FMC) at the 13th embryonic day (ED 13). At ED 15, some cuboidal mesothelial cells (CMC) and immature lymphatic stomata (NLS) were found scattered on the diaphragmatic mesothelium. The sub-peritoneal lymphatic capillaries did not appear until ED 18. However, no absorptive function was observed in NLS when trypan blue granules were injected into the peritoneal cavity. At postnatal day 1 (PND 1), the endothelial cytoplasm processes of the diaphragm lymphatic capillaries span the connective tissue fibers and the basal membrane of CMC to form the subperitoneal channels. These channels were connected with NLS and serve as the absorptive route between the peritoneal cavity and the sub-peritoneal lymphatic vessels. The trypan blue absorption test demonstrated that postnatal PLS possessed an absorptive function and had transformed to mature lymphatic stomata (MLS) by PND 1. Thus, NLS were renamed of MLS. At PND 5, the cuboidal mesothelial cell ridge (CMCR) appeared with increased CMC areas. At PND 10, CMCR were fused to form the band-like CMC area with much more MLS distributed in the muscular portion of the diaphragm. With distribution area and density of PLS increasing and growth of lymphatic vessels, an increased absorptive function from the peritoneal cavity was observed in the experiment.