米酵菌酸中毒小鼠顶叶皮质超微结构观察

目的观察米酵菌酸对小鼠顶叶皮质毒性作用的超微结构改变,探讨米酵菌酸的中毒作用机理。方法小鼠腹腔注射米酵菌酸,2h后取其大脑皮质,常规透射电镜样品制备,电镜观察其组织的超微结构。结果米酵菌酸主要损伤皮质神经元、胶质细胞和毛细血管内皮细胞的线粒体、粗面内质网及突触等结构。可见线粒体肿胀,嵴断裂或消失,部分线粒体髓样变和空泡变性;粗面内质网数量减少;核周间隙局部增宽;血脑屏障毛细血管周间隙扩张,呈空亮的囊泡样结构,内皮细胞微绒毛减少;突触小泡减少。结论米酵菌酸可造成脑组织亚细胞结构的损伤,为米酵菌酸中毒引起的神经中毒机理提供形态学依据。     

糖尿病大鼠味腺超微结构的研究

目的观察2型糖尿病大鼠味腺超微结构变化。方法雄性Wistar大鼠18只,随机分为对照组和实验组,高脂喂养加小剂量链脲佐菌素(STZ)腹腔注射制备2型糖尿病模型,饲养8周后取轮廓乳头,应用透射电镜观察味腺超微结构。结果与对照组大鼠比较,实验组大鼠味腺腺泡细胞的核膜凹陷、核固缩;线粒体嵴断裂、空泡变性;粗面内质网扩张,脱颗粒。结论糖尿病可导致味腺组织出现一系列超微结构病理改变,为进一步探讨糖尿病发生机制提供了形态学依据。     

景垂片对小白鼠四氯化碳中毒后肝细胞的电镜观察

本文主要研究景垂片对小白鼠四氯化碳中毒后肝细胞超微结构的变化,实验结果如下:四氯化碳中毒后肝细胞的超微结构中以细胞核、线粒体、内质网及糖元等为主要变化。细胞核的核膜不规则呈锯齿状,染色质浓集成块状,甚至核溶介。线粒体广泛变性肿胀,嵴不清楚,有的嵴消失,基质透明甚至空泡化。粗面内质网呈囊状扩张,其膜上附着的核蛋白体脱落,滑面内质网也轻度扩张。其周围糖元明显减少。用景垂片治疗的小白鼠肝细胞接近正常,核圆形,核膜光滑,线粒体嵴清楚,细胞间可见清楚的桥粒结构,粗面内质网平行排列,膜上附着大量核蛋白体颗粒,滑面内质网分散于细胞质中,糖元颗粒丰富,所以景垂片对肝细胞有保护作用。     

酒精对大鼠胚胎肝脏超微结构的影响

本文应用透射电镜技术，研究和观察了酒精对大鼠胚胎肝细胞超微结构的影响。结果发现，酒精对大鼠胚胎肝细胞有明显的损伤作用。主要表现为：粗面内质网扩张，数量明显减少，并有脱颗粒现象；滑面内质网扩张呈空泡状；线粒体肿胀、变形，结构遭到破坏；糖原颗粒明显减少，甚至消失。     

氨对培养胚鼠大脑神经元形态的影响

为研究氨对培养神经元的影响，并探讨神经元形态改变在肝性脑病发生中的作用。通过对胚胎大鼠大脑神经元的分散培养，结合光镜，透射电镜及免疫组织化学法，观察了氨对分散培养胚鼠大脑神经细胞的影响，发现氨可引起神经元胞体肿胀，尼氏小体溶解，胞质内出现颗粒及空泡变性，甚至突起崩解，核固缩，细胞坏死脱落；电镜下示细胞内内质网，线粒体扩张及囊性变，粗面内质网脱颗粒，大量致密小体出现，突起肿胀，微丝减少；神经微丝蛋白及突触体素的表达减少。实验结果表明，氨对培养神经元具有一定毒性作用，神经元的病变可能影响了其正常功能，促使肝性脑病的发生。     

假密环菌多糖Y-HW抗ConA诱导小鼠实验性肝损伤的形态学研究

目的 验证假密环菌多糖Y-HW的护肝作用.方法 应用光镜和电镜技术对假密环菌多糖Y-HW对ConA诱导的小鼠实验性肝损伤的拮抗作用进行形态学观察.结果ConA诱导的肝损伤模型组超微结构表现为肝细胞肿胀,脂肪变性;胞浆疏松和粗面内质网脱颗粒;线粒体数目增多且呈现出明显肿胀和嵴少,而预先用假密环菌多糖组超微结构表现:肝细胞的上述各种变性坏死明显减轻,肝细胞除少数线粒体轻度肿胀外,粗面内质网接近正常未见脂肪变性.结论 假密环菌多糖Y-HW对ConA引起的肝损伤有拮抗作用,为临床筛选护肝药物提供了形态依据.     

异叶青兰作用后的缺氧大鼠海马超微结构的定量分析

本文采用图像定量分析和形态测量方法,对缺氧及服用中草药异叶青兰的大鼠海马CA3区超微结构进行形态定量观察.结果表明,缺氧组海马锥体细胞肿胀;粗面内质网脱颗粒、网池扩张、断裂,并且失去正常的绕核或平行成层的分布形式;线粒体明显肿胀、嵴断裂,数量减少,平均截面积增大;髓鞘变性,轴突和树突内线粒体肿胀明显;轴棘、轴树突触间隙宽度变窄.缺氧给药组海马锥体细胞无明显肿胀;线粒体数量增多,平均截面积无明显增大,线粒体嵴结构完整.本文对各组形态变化的差异进行了探讨.     

海马CA1区锥体细胞的衰老性变化：——超微结构定量分析

本文应用光镜和电镜观察结合形态计量学及体视学的研究方法对青年组。老年组。ＳＤ大白鼠海马ＣＡ１区锥体细胞进行研究。结果显示老年组ＣＡ１区２５ｕｍ区段锥体细胞数、核仁体积、粗面内质网面密度均比青年组减少，脂褐素体密度比青年组增加。电镜下见老年组海马ＣＡ１区锥体细胞内的粗面内质网出现脱颗粒、双层膜之间间隔增宽、线粒体肿胀等细胞器的变化，表明海马ＣＡ１区锥体细胞退变化其它脑区更严重。本文并对锥体细胞丢失退     

大鼠松果体衰老的形态学研究

目的 探讨松果体形态结构的衰老性变化,为进一步研究松果体与衰老的关系提供形态学基础。方法 随机选取3月龄和34月龄SD大鼠10只分别作为青年组和老年组,用光镜和电镜结合形态计量学分法分析松果体细胞和神经胶质细胞密度及其指数;松果体细胞线粒体的Vv、Sv、Nv,高尔基器的Vv、Sv、粗面内质网的Sv、溶酶体的Vv;松果体神经终末的Vv及其线粒体的Vv、Sv、Nv、小颗粒囊泡的NA。结果 与青年组相比,老年组松果体细胞核形状不规则,核膜皱褶增多和加深。细胞浆内粗面内质网减少,排列紊乱,分散,脱颗粒明显;线粒体结构不清、肿胀、嵴断裂、消失、空泡化等。老年组松果体细胞密度比青年组减少,而神经胶质细胞密度增加,差异有高度显著性(P<0.01)。老年组神经胶质细胞指数比青年组高(P<0.01)。老年线粒体Vv与青年组无差别,但老年组线粒体Sv、Nv均比青年组减少(P<0.01)。老年组高尔基器的Vv、Sv均比青年组减少(P<0.01);老年组粗面内质网Sv比青年组减少,而老年组溶酶体Vv比青年组增加(P<0.01);老年组神经终末Vv比青年组减少(P<0.01);老年组神经终末中小颗粒囊泡NA比青年组减少(P<0.01);老年组线粒体Sv、Nv比青年组减少(P<0.05),两组神经终末中线粒体Vv无差别(P>0.05)。结论 老年大鼠松果体已发生衰老性变化,这可能与机?     

异叶青兰作用后的缺氧大鼠海马超微结构的定量分析

本文采用图像定量分析和形态测量方法，对缺氧及服用中草药异叶青兰的大鼠海马ＣＡ３区超微结构进行形态定量观察。结果表明，缺氧组海马锥本细胞肿胀；粗面内质网脱颗粒、网池扩张、断裂，并且失去正常的绕核或平行成层的分布形式；线粒体明显肿胀、嵴断裂、数量减少，平均截面积增大；增鞘变性，轴突和树突内线粒体肿胀明显；轴棘、轴树突触间隙宽度变窄。缺氧给药组海马锥体细胞无明显肿胀，线粒全数量增多，平均截面积无明显增大     

Spontaneous development of autoimmune sialadenitis in aging BDF1 mice.

This study reports that spontaneous autoimmune sialadenitis developed in aging female, rather than male, BDF1 mice. The lesions first appeared in 6-month-old female BDF1 mice and were aggravated with advancing age, especially in 24-month-old and 30-month-old senescent mice. In contrast, significant inflammatory changes did not develop in aging male BDF1 mice. The presence of antisalivary duct antibody was found in sera from mice with sialadenitis. The infiltrating cells in the lesions of submandibular salivary glands were mainly composed of T cells, especially Lyt 1+ and L3T4+ cells. Moreover, mild inflammatory lesions were observed in parotid, sublingual salivary glands, pancreas, or kidneys in some mice that developed spontaneously occurring sialadenitis.     

Class II MHC antigens in the rat digestive system. Normal distribution and induced expression after interferon-gamma treatment in vivo

The normal and interferon-gamma induced expression of class II MHC antigens was investigated immunohistologically in the digestive system of LEW rats. In the normal state class II molecules were present in interstitial dendritic cells, B lymphocytes and epithelial cells. Epithelial class II expression was restricted to enterocytes in certain portions of the small intestine and to some duct epithelia in salivary glands. After continuous intravenous infusion of interferon-gamma (IFN-gamma) for 3 days, class II MHC antigens were induced in large vessel endothelium and in the surface epithelia of the tongue, oesophagus and proventricle. In the gastric glands class II molecules appeared in mucous neck cells and in parietal cells, while adjacent mucous surface cells and chief cells did not acquire class II reactivity. All enterocytes, including the previously negative colonic epithelium, were induced to express class II antigens. In the salivary glands class II antigens appeared in all duct epithelia. Serous acinar cells were induced in the parotids, but in the submandibular glands and in the pancreas the serous gland epithelium stayed negative. Our study thus shows that the effects of IFN-gamma on class II MHC antigen expression in vivo depend on the differentiation pathway of the individual cell. The normal distribution in rats suggest that class II MHC antigens may play a role in peptide transport across specialized epithelia. It remains to be determined whether such a function is enhanced after IFN treatment.     

Aquaporins in the digestive system

Fluid transfer such as secretion and absorption is one of the major functions of the digestive system. Aquaporins are water channel proteins providing water transfer across the cellular membrane. At least six aquaporin isoforms are expressed in the digestive system. Aquaporin-1 (AQP1) is widely distributed in endothelial cells of capillaries and small vessels as well as in the central lacteals in the small intestine. AQP1 is also present in the duct system in the pancreas, liver, and bile duct. AQP3 is mainly expressed in the epithelia of the upper digestive tract from the oral cavity to the stomach and of the lower digestive tract from the distal colon to the anus. AQP4 is present in the parietal cells of the stomach and in the intestinal epithelia. AQP5 is expressed in acinar cells of the salivary, pyloric, and duodenal glands. AQP8 is expressed in the intestinal epithelia, salivary glands, pancreas, and liver. AQP9 is present in the liver and intestinal goblet cells. Aquaporins have important roles in the digestive system, such as AQP5 in saliva secretion, as shown by the studies on AQP5-null mice. In addition, water transfer across the digestive epithelia seems to occur not only via aquaporins but also via other transporter or channel systems.     

Pathology of the pancreas and other organs in the diabetic LEW.1AR1/Ztm-<Emphasis Type="Italic">iddm</Emphasis> rat,a new model of spontaneous insulin-dependent diabetes mellitus

We studied the histo- and immunopathology of the endocrine and exocrine pancreas and a number of other organs in a new insulin-dependent diabetes mellitus (IDDM) rat model (LEW.1AR1/Ztm-iddm rat). The pancreas of the acutely diabetic animals showed an inflammatory infiltrate, involving all islets and ducts. The islet infiltrate was composed mainly of ED1-positive macrophages and T lymphocytes, comprising a large number of CD8⁺ lymphocytes and a few CD4⁺ lymphocytes. In addition, the islets displayed apoptotic cells, characterized by condensation and fragmentation of nuclear chromatin. These cells were identified as beta cells by insulin immunostaining. Other endocrine and exocrine glands, including adrenals and thyroid, as well as salivary and submandibular glands, were unaffected. Organs from the digestive tract or systemic circulatory system, including small intestine, liver, heart, and lung also showed no involvement. The kidney was intact in acutely diabetic rats. However, 6 months after diabetes manifestation, pathological changes compatible with a diabetic nephropathy had developed, affecting both the glomerula and the proximal tubular segments. It was concluded that the autoimmune process in this new IDDM rat model is restricted to the endocrine pancreas and leads to apoptotic beta cell destruction.     

Immunohistochemical localization of translationally controlled tumor protein in the mouse digestive system

Translationally controlled tumor protein (TCTP) is a housekeeping protein, highly conserved among various species. It plays a major role in cell differentiation, growth, proliferation, apoptosis and carcinogenesis. Studies reported so far on TCTP expression in different digestive organs have not led to any understanding of the role of TCTP in digestion, so we localized TCTP in organs of the mouse digestive system employing immunohistochemical techniques. Translationally controlled tumor protein was found expressed in all organs studied: tongue, salivary glands, esophagus, stomach, small and large intestines, liver and pancreas. The expression of TCTP was found to be predominant in epithelia and neurons of myenteric nerve ganglia; high in serous glands (parotid, submandibular, gastric, intestinal crypts, pancreatic acini) and in neurons of myenteric nerve ganglia, and moderate to low in epithelia. In epithelia, expression of TCTP varied depending on its type and location. In enteric neurons, TCTP was predominantly expressed in the processes. Translationally controlled tumor protein expression in the liver followed porto‐central gradient with higher expression in pericentral hepatocytes. In the pancreas, TCTP was expressed in both acini and islet cells. Our finding of nearly universal localization and expression of TCTP in mouse digestive organs points to the hitherto unrecognized functional importance of TCTP in the digestive system and suggests the need for further studies of the possible role of TCTP in the proliferation, secretion, absorption and neural regulation of the digestive process and its importance in the physiology and pathology of digestive process.     

不同移植途径对人脐带间充质干细胞防治NOD鼠糖尿病的影响

目的观察不同移植途径对人脐带间充质干细胞(hUCMSCs)预防非肥胖型糖尿病(NOD)小鼠糖尿病发病的影响并进一步探索其机制。方法通过胰腺包膜下和尾静脉向4周龄雌性NOD小鼠注射hUCMSCs-EGFP/luc,活体成像观察hUCMSCs的分布。动态监测NOD小鼠血糖水平变化以及Treg/Th17细胞变化,在30周龄时处死小鼠进行胰腺炎评级。结果胰腺移植组在30周龄时糖尿病发病率显著低于尾静脉移植组和对照组。2种途径移植组小鼠Treg细胞呈升高趋势,明显高于对照组,而Th17细胞明显低于对照组,2种移植途径组间无明显差异。病理学发现胰腺组胰腺炎评分最低,对照组最高,移植组胰腺炎性损伤明显减轻。结论 hUCMSCs经2种途径移植后,均能明显降低NOD鼠糖尿病的发生率和延缓发病时间,且胰腺移植组效果显著。除hUCMSCs主要通过诱导Treg细胞抑制Th17细胞发挥免疫抑制作用,阻止自身免疫对胰岛β细胞的攻击外,可能与到达胰腺组织的细胞对胰腺β细胞的保护和损伤修复作用也具有一定关系。     

Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells

The emergence of cells with hepatocellular properties in the adult pancreas has been described in several experimental models. To determine whether adult pancreas contains cells that can give rise to therapeutically useful and biochemically normal hepatocytes, we transplanted suspensions of wild-type mouse pancreatic cells into syngeneic recipients deficient in fumarylacetoacetate hydrolase and manifesting tyrosinemia. Four of 34 (12%) mutant mice analyzed were fully rescued by donor-derived cells and had normal liver function. Ten additional mice (29%) showed histological evidence of donor-derived hepatocytes in the liver. Previous work has suggested that pancreatic liver precursors reside within or close to pancreatic ducts. We therefore performed additional transplantations using either primary cell suspensions enriched for ducts or cultured ducts. Forty-four mutant mice were transplanted with cells enriched for pancreatic duct cells, but only three of the 34 (9%) recipients analyzed displayed donor-derived hepatocytes. In addition, 28 of the fumarylacetoacetate hydrolase-deficient mice were transplanted with cultured pancreatic duct cells, but no donor-derived hepatocytes were observed. Our results demonstrate for the first time that adult mouse pancreas contains hepatocyte progenitor cells capable of significant therapeutic liver reconstitution. However, contrary to previous reports, we were unable to detect these cells within the duct compartment.     

Predominance of T lymphocytes in pancreatic islets and spleen of pre-diabetic non-obese diabetic (NOD) mice: a longitudinal study.

We examined sequential changes in the subsets of mononuclear cells infiltrating the pancreatic islets and splenic lymphocytes in pre-diabetic non-obese diabetic (NOD) mice, an animal model for type I diabetes, using immunofluorescent techniques. In the pancreas, a predominant infiltration by activated T lymphocytes, including helper inducer and cytotoxic suppressor T cells, was observed in the early stage of insulitis. Natural killer cells were also detected in the lesions. Immunoglobulin bearing cells tended to increase in number with the progression of insulitis. T lymphocytes were localized close to islet cells, while immunoglobulin bearing cells appeared adjacent to blood vessels and around T cell clusters. Immunoglobulin deposition or Ia expression on islet cells was not observed. The percentage of splenic T lymphocytes was markedly increased in the initial stage of insulitis as compared with control ICR mice and this elevated proportion of T cells continued throughout the observation period. As for splenic T cell subsets, cytotoxic suppressor T cells were increased in NOD mice. These results suggest that T lymphocytes play an important role in the initiation of insulitis long before the onset of overt diabetes. Moreover, NOD mice seem to have characteristic immunological features different from the BB rat or a reported case with human type I diabetes.     

糖尿病小鼠胰岛β细胞结构的光镜和电镜研究

目的观察2型糖尿病模型db/db小鼠胰岛β细胞的超微结构、胰岛素表达及数量变化,探讨β细胞的病理改变与2型糖尿病病因的关系。方法分别选取3、5、8月龄尾静脉空腹血糖高于10.1mmol/L,且肥胖的db/db自发性糖尿病小鼠,每组8只,作为糖尿病组;选取相应年龄段尾静脉空腹血糖低于6.0mmol/L,体重正常的db/+m表型正常小鼠,每组8只,作为对照组。于相应年龄段取胰尾,用于透射电镜观察、免疫组织化学观察和图像分析。结果电镜下随病情进展,db/db小鼠胰岛β细胞内的分泌颗粒数量明显减少,有的细胞甚至缺如,致密芯电子密度降低,β细胞可见凋亡的早期改变以及细胞核和细胞器的病理改变,细胞间髓样小体增多。免疫组织化学显示同月龄糖尿病组小鼠胰岛β细胞阳性率和胰岛素蛋白平均光密度值(OD值)低于相应对照组(p<0.05),且随着病程的进展,db/db小鼠胰岛β细胞阳性率和胰岛素表达呈现递减趋势(p<0.05)。结论2型糖尿病β细胞的超微结构遭到破坏,引起β细胞合成分泌胰岛素障碍和数量减少,与2型糖尿病病情的轻重有关,反映了2型糖尿病病程不同阶段的病机特点。