【作者】 刘鹏；

【导师】 李黎明；

【作者基本信息】 天津医科大学 ， 外科学， 2008， 硕士

【摘要】 背景与目的原醛症是继发性高血压的常见原因之一,在亚洲高血压患者群中原醛症的发病率为5%～13%,而至少一半的受试者血钾浓度正常。肾上腺皮质腺瘤(APA)和增生(IHA)是原醛症最常见的两种亚型。肾上腺皮质腺瘤患者手术方法能治愈,而皮质增生需要以药物治疗为主结合手术但复发率较高。因此,鉴别肾上腺皮质腺瘤和增生对于临床工作有重要的意义。但是其临床表现相似,多呈高醛固酮血症、高血压或低血钾等,明确鉴别依据术后病理。我们前期研究已经有效地筛选出原醛症中肾上腺皮质腺瘤和增生的差异表达基因,并确定一些基因的身份及功能,国内首次构建原发性醛固酮增多症基因文库。此外,我们还发现,在光学显微镜下两者的病理有一些差异;同时这两种病变的激素分泌有较多不同,因此可能这两者病变的发生、发展和不同超微病理结构相关联。方法组织标本均分为两份,一份行光学显微镜病理学检查,病理组织切片HE染色由两位有经验的临床病理学专家阅片作出病理诊断。另一份经过取材、固定、脱水、浸透、包埋、切片及染色等步骤,制成超薄切片,行透射电镜扫描,明确这两种病变的超微结构的差异。本实验对原醛症这两种亚型分别进行光镜及电镜的比较,获得肾上腺皮质腺瘤和增生之间的超微结构的差异。结果肾上腺皮质腺瘤的光镜特点:主要部分由“杂交细胞”构成,多见大透明细胞,另一种细胞体积小胞浆中见有颗粒,还可见有嗜酸性细胞。电镜特点:细胞表面微绒毛增多,瘤细胞核以常染色质为主,核仁明显;胞质中见管泡状滑面内质网,短股的粗面内质网,细胞间关系密切见中间连接;球形、长形线粒体并具有长管泡状嵴、高尔基复合体明显、小堆状平行排列的粗面内质网,富于脂滴,直径1～2nm,明显的脂褐素颗粒,细胞器密度较高,主要为线粒体。可见着色较浅的嗜酸性细胞质包涵体可见嗜酸性细胞质包涵体——螺内酯小体,是细胞质内呈同心圆状排列的细胞器结构,直径约25 u m。肾上腺皮质增生的光镜特点:结节都无包膜,分布大都是呈散发性,以双侧皮质增生为主;增生的细胞主要为富含脂质的透明细胞,夹杂成堆的致密细胞,球状带弥漫性或灶性增宽。电镜特点:细胞胞核以常染色质为主,核仁明显、突出,胞质内有成堆排列的细长的滑面和粗面内质网,线粒体多见,呈球形或球面形且具有长管泡状嵴,脂滴较多,可见脂褐素颗粒。结论1.肾上腺皮质腺瘤的光镜特点:主要部分由所谓“杂交细胞”构成,兼有球状带细胞和束状带细胞的特点;多见大透明细胞,胞浆呈空泡状或颗粒状,核呈圆形、肾形或杆形,瘤细胞呈巢状,索状或腺样排列;另一种细胞体积小,胞浆中见有颗粒;还可见有嗜酸性细胞,位于纤维间隔。肾上腺皮质增生的光镜特点:结节都无包膜,分布大都呈散发性,病变以双侧皮质增生为主。增生的细胞主要为富含脂质的透明细胞,夹杂成堆的致密细胞,球状带弥漫性或灶性增宽。2.肾上腺皮质腺瘤的肿瘤细胞在电镜下显示:细胞表面微绒毛增多;瘤细胞核以常染色质为主,核仁明显;胞质中见管泡状滑面内质网,短股的粗面内质网,细胞间关系密切见中间连接;球形、长形线粒体并具有长管泡状嵴、高尔基复合体明显、小堆状平行排列的粗面内质网,富于脂滴,细胞器密度较高,主要为线粒体,有明显的脂褐素颗粒。可见嗜酸性细胞质包涵体——螺内酯小体,是细胞质内呈同心圆状排列的细胞器结构,直径约25 u m。肾上腺皮质增生的细胞电镜特点:细胞核以常染色质为主,核仁明显、突出,胞质内有成堆排列的细长的滑面和粗面内质网,线粒体多见,呈球形或球面形且具有长管泡状嵴,脂滴较多,可见脂褐素颗粒。结合文献资料,肾上腺皮质线粒体显示了一种普遍的形态适应功能的能力,产生醛固酮的细胞出现大量的长管状的线粒体伴内膜架桥,形成层状嵴。3.本研究应用透射电镜等技术研究原醛症肾上腺皮质腺瘤和增生两种亚型的超微结构,对于深入研究原醛症肾上腺皮质腺瘤和增生两种亚型临床表现差异提供组织病理学及亚细胞超微病理学的基础科研资料。更多还原

【Abstract】 Background and ObjectivePrimary aldosteronism is one of the most reason of symptomatic hypertension, recently in hypertensive populations suggested that the prevalence may be 5%～13% in Asia. The most common clinical subtypes of primary aldosteronism are APA and adrenal cortical hyperplasia (or IHA). The patients of APA can be cured by operation. But the patients of IHA should be treated by both drug treatment and operation,and the recurrence rate of IHA is also very high. So the discrimination of these two disease has very important significance in clinic. The clinical manifestation of these two diseases both are high blood pressure, hyperaldosteronemia, and hypokalemic,so it made the clinic diagnos difficultly. At present, we only depend on pathobiology of specimen after operation to discriminate. Because they have highly discrimination in pathology of optical microscope and hormone secretion, we think that the occurrence and the development of these two diseases must be related by different ultrastructure.MethodsThe APA and IHA specimens are divided into two pieces. One is undertaked by the optic-microscope pathology study for pathological diagnosis. Another is made into ultrathin section by draw the materials, fixation, dehydration, soak, embedment, slice and dyeing and so on; then we can get some images by the transmission electron microscopy; at last we can clear the different ultrastructure of these two diseases. In my experiment, these two diseases were compared with the same normal adrenal gland, so we could compare the APA to IHA by using these data. Then,the different ultrastructure of these two diseases is clear.ResultsThe APA,in the histology, the majority of tumor cells are similar to the normal zona glomerulosa or zona fasciculata cells. But in the electron microscope,these cells have the special characters: the plastosome of globular or long and of long tracheid crista, obvious Golgi complex, a heap of parallel disposed rough endoplasmic reticulum, many lipid droplets,obvious lipofuscin granulation, sometimes intranuclear pseudo-inclusion body also can be see. Adrenal cortical hyperplasia cells are mainly abundant of lipidic cellule clear. In the electron microscope, a heap of smooth endoplasmic reticulum and rough endoplasmic reticulum in the hyperplastic cells and tracheid crista plastosome. We thought, plastosome of the adrenal cortex shows a common adaptive function and these aldosterone- producing tumor cells have a mass of lamellar crista of plastosome.Conclusions1. The adrenocortical adenoma, in the optical microscope, most of are hybrid cells: hyaline cell often is the most and another cell also exist. Adrenal cortical hyperplasia, in the optical microscope, has a characteristic of no envelope, sporadic tubercle and bilateral pathological changes.2. The adrenocortical adenoma, in the electron microscope,these cells have the special characters: the plastosome of globular or long and of long tracheid crista, obvious Golgi complex, a heap of parallel disposed rough endoplasmic reticulum, many lipid droplets,obvious lipofuscin granulation, sometimes intranuclear pseudo-inclusion body also can be see. Adrenal cortical hyperplasia cells in the electron microscope, a heap of smooth endoplasmic reticulum and rough endoplasmic reticulum in the hyperplastic cells and tracheid crista plastosome. We thought, plastosome of the adrenal cortex shows a common adaptive function and these aldosterone- producing tumor cells have a mass of lamellar crista of plastosome.3.Transmission electron microscopy can effiectively find out different ultrastructure of the subtypes in primary aldosteronism. It is important significance to investigate the subtypes. It gives us great scientific research information to investigate the diseases.更多还原