四氯化碳诱导性肝纤维化大鼠肝组织骨形态发生蛋白-7的表达

目的 探讨四氯化碳(CCl4)诱导性肝纤维化大鼠的肝组织纤维化与骨形态发生蛋白-7(BMP-7)表达的相互关系.方法 将健康雄性 Wistar 大鼠随机分为对照组和肝纤维化组.对照组大鼠每周一、四背部皮下注射橄榄油(0.12ml/100g),肝纤维化组每周一、四背部皮下注射60% CCl4橄榄油(0.3ml/100g),连续注射6、10、16 和21周.实验结束时处死大鼠,取肝中叶,石蜡包埋、切片.行天狼猩红染色,观察肝组织胶原纤维的增生情况;行BMP-7免疫组织化学染色和 Western blotting 检测,观察肝组织.BMP-7的表达.结果 天狼猩红染色显示对照组大鼠仅在肝门静脉及门管区看到少量的胶原纤维,各肝纤维化组大鼠均可见肝组织呈明显的胶原纤维增生,且随着时间的延长,肝纤维化程度逐渐加重;免疫组织化学染色显示,对照组大鼠肝组织中可见极少量的BMP-7表达阳性的细胞,6周肝纤维化组大鼠可见较多的BMP-7阳性表达细胞,但随着实验时间的延长,BMP-7阳性细胞呈递减的趋势,至21周肝纤维化组大鼠肝组织中基本呈阴性表达;Western blotting 法检测大鼠肝组织BMP-7的表达结果与免疫组织化学的结果基本一致.结论 CC14诱导性肝纤维化大鼠肝组织BMP-7的表达与肝纤维化的程度呈负相关的趋势,推测BMP-7可能对肝纤维化具有一定的保护作用.     

MORPHOGENESIS OF SEPTA IN HEPATIC FIBROSIS INDUCED BY CHOLINE DEFICIENCY IN RATS

Examination of hepatic fibrosis Induced by choline deficient diet showed the histogenesis of early flbrosis and septa formation. Male rats were fed a choline deficient diet. Groups of three were sacrificed after 1, 2, 3, 6, 8, 12, and 13 weeks. Control groups of three rats were sacrificed after 6, 8, and 12 weeks. All choline deficient rats showed initial steatosis around the portal tracts. The fat droplets were small at first and gave a microvesicular appearance. As they grew, they gathered around the terminal hepatic venule by the 3rd week. Then, retlcular fibers developed around the hepatocytes in the centrolobular area and fibroses connected the terminal hepatic venules. The fat droplets became larger and made nodular masses around the portal tract. These compressed the fibroses to the periphery where they formed septa. After 12 weeks, regenerating nodules developed. Electron microscopy showed that fat storing cells helped cause pericellular fibrosis.     

内霉素诱发肝性脑病大鼠脑超微结构观察

目的：观察内毒素诱发肝硬化大鼠发生肝性脑病时血脑屏障超微结构变化。方法：用小剂量内毒素（３ ｍｇ／ｋｇＢＷ）一次性腹腔内注射诱发肝硬化大鼠发生肝性脑病。取部分大脑皮层组织制备超薄切片,在电子显微镜下观察其超微结构变化。结果：肝性脑病大鼠脑微血管明显扩张,内皮皱折增多,内皮下基底膜电子密度降低,甚至局部溶解消失。微血管周围星状胶质细胞突起及皮层内胶质细胞明显肿胀,细胞器成分减少,基质解聚。结论：内毒素诱发肝性脑病时,脑超微结构确有明显变化。这些变化提示,肝性脑病发生时,血脑屏障通透性增加;同时,脑胶质细胞呈现水肿。内毒素血症有可能是各种肝性脑病发生机制学说的共同基础。     

根皮苷对日本血吸虫感染小鼠肝纤维化的抑制作用

探讨根皮苷对日本血吸虫感染所致小鼠肝纤维化的保护作用。随机将未感染和感染日本血吸虫尾蚴昆明小鼠分成4组A—D,每组10只：未感染空白对照组（A）、模型组（B）、复方鳖甲软肝片阳性组（C）、根皮苷治疗（40mg/（kg·d））组（D）。感染后第42d,B、C、D组均用吡喹酮驱虫治疗500113tg／（kg·d）,2日疗法,之后各组开始灌胃给药持续治疗60d,A和B组生理盐水灌胃对照。实验结束处死小鼠,留取肝脏组织和血清,测定血清中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、透明质酸（HA）含量,计算肝体指数,测定肝组织中羟脯氨酸（HYP）含量。苏木素-伊红和Masson胶原纤维染色观察小鼠肝组织变性、虫卵肉芽肿与胶原沉积等病理改变。结果显示,与A组相比,B、C、D组小鼠肝脏有明显虫卵肉芽肿形成、胶原沉积与肝纤维化,伴有不同程度肝细胞炎性损伤坏死。血清中ALT、AST、HA和肝组织中HYP含量均明显升高（P〈0．05或P〈0．01）。与B组相比,根皮苷组ALT、AST、HA和HYP含量和肝体指数均明显降低（P〈0．05或P〈0．01）,肝组织坏死与胶原沉积明显减轻,虫卵肉芽肿面积减小。结果表明根皮苷具有抗血吸虫性肝纤维化的作用。     

切断大鼠交感神经对动脉粥样硬化形成的影响

将雄性Ｗｉｓｔｒ大鼠１２只分成实验组和对照组，实验组行手术切断左侧颈交感干，两天后与对照组同时腹腔注射维生素Ｄ６０万单位／ｋｇ体重，存活２０天后取双侧颈总动脉作石蜡切片，ＨＥ染色，光镜下观察，结果发现：实验组颈总动脉壁明显增厚，相当于正常血管壁的３－５倍，弹性纤维结构不清，甚至消失，内膜一层水肿并有胶原纤维增生，中膜有大量平滑肌细胞增生，其细胞核排列紊乱。     

EXPERIMENTAL ANALYSIS ON PATHOGENESIS OF THE SECONDARY NODULE LESIONS IN LYMPH NODES INDUCED BY SHOCK

Various animal experiments were undertaken with the object of clarifying the pathogenesis of cellular destruction and resultant atrophy of secondary nodules in lymphatic tissues appearing in shock. Reproduction of such changes were successfully performed in the experiments of hemorrhagic shock and endotoxin shock. From the results of experiments on various types of hypoxia, it was deduced that the karyorrhetic phenomenon and sequential atrophy of secondary nodules are closely related to such a hypoxia. Vascular ligation of the lymph node and experiment under high oxygen pressure led to a conclusion that lymphatic tissue anoxia usually occurring during shock plays a more important role in production of such a phenomenon in the secondary nodules than the direct effect of oxygen supply from the secondary nodule arterioles.     

Fos蛋白在血管加压素诱发急性心肌缺血大鼠脑内的分布

目的 研究与急性心肌缺血功能有关的神经元在大鼠脑内的分布。方法 股静脉注射管加压素诱发大鼠急性心肌缺血,用免疫组织化学ＡＢＣ法,观察Ｆｏｓ蛋白在脑内的表达和分布。结果 Ｆｏｓ阳性产物分布于梨状皮质、伏核、终纹床核、扣带回、斜角带核、下丘脑室旁核、视上核、视交叉上核、弓状核、中央杏仁核、穹窿下器、丘脑室帝核、外侧缰核、中脑中央灰质腹外侧区、脑桥臂旁外侧核、蓝斑、延髓内脏带等脑区,而在大脑白质及小脑中     

A ROLE FOR APOPTOSIS INDUCED BY ACUTE HERPES SIMPLEX VIRUS INFECTION IN MICE

Acute herpes simplex virus (HSV) infection causes apoptosis in the adrenal cortex and myenteric plexus of the gut, ovary, pituitary gland, and liver of mice. Apoptosis of infected cells is increased in immunosuppressed regions of the adrenal cortex and liver of macrophage-depleted mice. HSV carries the US3 gene which interferes with host cell apoptosis. When the livers of macrophage-depleted mice are infected with a US3-null virus, apoptosis occurs in the narrow areas of inflammatory cell infiltration, restricting viral replication and spread. Thus, these data suggest that apoptosis may function as a primitive immune response to HSV infection in mice.     

DIISOPROPANOLNITROSAMINE (DIPN) INDUCED RAT THYROID LESIONS

DIPN induced localized lesions of the rat thyroid gland are described histologically and classified into three major types: type 1, foci of cellular alteration; type 2, proliferative nodules; and type 3, overt carcinomas. Follicular, papillary and mixed papillofollicular subtypes are recognized in the type 2 lesions, and follicular, papillary, anaplastic and mixed subtypes in the type 3 lesions. The nature of the individual lesions is discussed.     

DIISOPROPANOLNITROSAMINE (DIPN) INDUCED RAT THYROID LESIONS

An ultrastructural study was carried out on DIPN induced lesions of rat thyroid glands, in order to characterize in detail each type or subtype as classified by light microscopy in our previous report. Organelles closely related to the endocrine function of the thyroid epithelium such as apical or subapical vesicles, lysosomal granules, colloid droplets, Golgi apparatus, rER, and microvilli on the apical surface, were found to decrease in parallel with structural and cellular atypism of the thyroid lesion under examination, suggesting impairment of their function in the malignant lesions. On the other hand, observations of transitional forms among the lesions in term of the subcellular structure were considered to support the possibility that transformation from one type to another could occur.     

AN ULTRASTRUCTURAL STUDY ON PRECANCEROUS AND CANCEROUS LESIONS OF THE GLANDULAR STOMACH IN RATS INDUCED BY N-METHYL-N'-NITRO- N-NITROSOGUANIDINE

Electron microscopic study was made on precancerous and cancerous lesions in glandular stomach of rats induced by MNNG. Three types of lesions, were found; regenerative glandular hyperplasia, adenomatous hyperplasia and adenocarcinoma. These were compared with the fine structure of similar lesions produced by X-irradiation in the glandular stomach of mice. The precancerous lesion in the present study demonstrated formation of adenomatous hyperplasia by epithelial cells which included mucoid cells characterized by sparce surface microvilli, a few erratic terminal webs, small number of mucous granules, many small mitochondria, and a bizarre nucleus. The development of these mucoid cells seems to be related with the growth of gastric carcinoma. The ultrastructure of adenocarcinomas revealed many structural variations or abnormalities of cellular differentiation. They were classified into 1) surface and pit mucous cell type, 2) pyloric gland cell type, 3) goblet cell type, 4) paneth cell type, 5) intestinal epithelial cell type, 6) endocrine cell type, 7) oncocyte type, 8) filament-rich cell type, and 9) anaplastic cell type involving intracellular microcyst cells. Filament-rich cells were found in poorly differentiated adenocarcinoma or scirrhous carcinoma and may be derived from metaplasia of tumor cell.     

人肝干细胞移植增加四氯化碳诱导性肝硬化大鼠白蛋白表达

目的 旨在研究人胚胎肝干细胞移植入四氯化碳(CCl4)诱导性肝硬化大鼠的肝组织后,大鼠血清及肝组织血清白蛋白(ALB)表达的变化情况.方法 将健康雄性Wistar大鼠随机分为对照组和肝硬化组.对照组背部皮下注射橄榄油,CCl4组背部皮下注射CCl4橄榄油.连续注射6周后,肝硬化组再随机分为肝干细胞假移植组和肝干细胞移植组.对照组和假移植组在大鼠肝中叶注射细胞培养液,而移植组则在相应部位注射人胚胎肝干细胞2×106,移植4周后处死所有大鼠.右心室取血离心观察ALB的含量;肝中叶取材,免疫组织化学染色观察人表皮生长因子受体(EGFR)的表达,免疫荧光染色和免疫印迹法(Western blotting)法观察和测定肝组织ALB的表达变化.结果 对照组和肝干细胞假移植组未见人EGFR阳性表达的细胞,肝干细胞移植组则可见大量排列成环状的EGFR阳性表达的细胞.在肝干细胞移植组的血清ALB含量、免疫荧光染色及Western blotting法检测肝组织ALB表达,均明显高于假移植组,而与对照组无明显著异.结论 将人胚胎肝干细胞移植入肝硬化大鼠肝内可以长期存活,并可改善大鼠ALB的表达和分泌.     

EXPERIMENTAL STUDIES ON TUMORS OF THE URINARY SYSTEM OF RATS INDUCED BY CHEMICAL CARCINOGENS*

Tumors in rats were induced in the urinary system of rats with basic lead acetate (BLA), N-nitrosodimethylamine (DMN), N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), N-nitrosodibutylamine (DBN), 3-methylcholanthrene (3-MC) and 4-nitroquinollne 1-oxide (4NQO). These kidney, ureter and urinary bladder tumors were studied by histopatho-logy, histochemistry, autoradiography and electron microscopy. The tumors of the kidney were classified into the following 4 types; renal cell tumors, embryonal cell tumors, transitional cell tumors and hemangioendotheliomas. However, the tumors of all other regions were of one type, transitional cell tumors. Studies by light and electron microscopy and autoradiography and histochemlcal studies on the histogenesis of tumors of the urinary system in rats showed that renal cell tumors may originate from the renal tubular epithelium and from a part of the metanephrogenic tissue, embryonal cell tumors originate from metanephrogenic tissue and hemangioendotheliomas may originate from blood capillaries. Transitional cell tumors of the kidney, renal pelvis, ureter and bladder originate from transitional epithelium.     

EXPERIMENTAL AMYLOIDOSIS INDUCED BY SAPONIN

White male rabbits, weighing about 3 kg, were injected intravenously with 5 ml of 0.1% saponin solution dissolved in physiological saline once a week for six months. The sequential histological changes in the kidneys were observed by repeated biopsies and, in addition, the animals were subjected to necropsy for light and electron microscopic examinations. Amyloid protein was purified from the animal tissues, estimated at approximately 6,300 daltons in molecular weight by SDS-PAGE and considered as an AA type protein based on its amino acid sequence study. The antibody against the purified amyloid protein was produced in guinea pigs and was used for immunohistochemical studies. The deposition of amyloid started initially in mesangial matrices and subendothelial regions of the glomeruli, but at the end the spleen, kidney and bowels were found to be frequent sites of deposition. The amyloid deposited in the tissues was specifically positive by the indirect immunohistochemistry using the prepared antibody. This antibody also reacted positively to human materials with secondary amyloidosis. These results indicate that amyloidosis induced by saponin is a good model of secondary amyloidosis.     

PULMONARY LESIONS IN RATS CAUSED BY INTRAVENOUS INJECTION

Sprague-Dawley rats in a chronic toxicity test revealed specific pulmonary lesions after 180 days of intravenous injection of samples via the tail vein. Microscopically, thickening of arterial walls, periarteritis, edema of perivascular sheath, arteriosclerosis, vasodilatation, arteriofibrosis, abscess and necrosis of arterial walls, embolism and thrombus of small muscular artery or alveolar capillary, and granulomas sometimes accompanying giant cells were found in the lungs. The emboli consisted of hair of the rats, and granulomas with multinucleated giant cell formation and cellular infiltration were prominent around the emboli. The thrombi was characterized by perivascular cuffing, fibrinous and cellular components. These pulmonary lesions are thought to be caused by hair brought from the tail when intravenous injection was carried out.     

SCANNING ELECTRON MICROSCOPIC STUDY OF PRECANCEROUS and CANCEROUS PANCREATIC LESIONS INDUCED BY N-NITROSOBIS (2-OXOPROPYL) AMINE IN SYRIAN GOLDEN HAMSTERS

Sequential alteration of Syrian golden hamster pancreatic ducts and ductules was investigated by scanning electron microscope during and subsequent to 10 weekly subcutaneous injections of N-nitrosobis (2-oxopropyl) amine (BOP). By examining surface morphology of ductal cells and resin casts of the secretory branches arising from the common duct, a series of lesions ranging from slight derangement of the luminal dimensions and loss of cilia to marked projections of "finger-like" processes accompanied by pleomorphism at the cellular and microvilli levels and increase in numbers of goblet cells could be established. A ductal histogenesis is proposed on the basis of the present scanning electron microscopic and earlier light microscopic findings. ACTA PATHOL. JPN. 36: 1359–1366, 1986.