胰岛素抵抗大鼠血糖正常阶段多器官形态学研究
发布时间：2018-10-25 06:48
【摘要】： 研究背景 2型糖尿病(T2DM)是一种常见的代谢性内分泌疾病,其发病率、死亡率、致残率高,严重危害人类健康。胰岛素抵抗(IR)是T2DM发病的病理生理基础。1995年Stern提出了著名的“共同土壤”学说,认为糖尿病(DM)、高血压、冠心病、脂代谢异常、肥胖是在胰岛素抵抗这个共同土壤中“生长”出来的,即胰岛素抵抗为这些疾病的共同发病因素。IR是指需要超过生理量的胰岛素才能在胰岛素的效应器官产生生理效应。胰岛素抵抗持续存在可导致糖耐量异常和糖尿病的发生。 DM是引起终末期肾病、失明、非创伤性截肢的重要原因,因此DM慢性并发症严重影响患者的生活质量,给患者、家属及社会造成沉重的负担。我们前期的研究表明,高糖高脂(2H)和高糖高脂高盐(3H)饮食成功诱导IR大鼠动物模型,在IR发生后且血糖正常阶段,外周神经病变已经发生。我们推测在糖尿病前期胰岛素抵抗血糖正常阶段,多种器官已经存在病理改变。因此我们在前期高糖高脂(2H)和高糖高脂高盐(3H)饮食成功诱导IR大鼠动物模型的基础上,研究血糖正常时期多脏器的形态学改变,探讨其形态的变化与糖尿病并发的脏器损伤的关系。 目的 我们在成功地建立IR且血糖正常的大鼠模型的基础上,观察大鼠肾脏、晶状体及肝脏的形态结构变化情况。旨在为糖尿病引起的脏器损伤的预防提供实验基础,为糖尿病前期的治疗提供理论依据。 方法 成功制作IR抵抗大鼠模型,采用光镜、透射电镜、扫描电镜技术,研究肾脏、晶状体、肝脏的形态学变化。 结果 1. 2H组肾小球、肾小管基底膜明显增厚,分别为(2.23±0.88)μm,(0.86±0.25)μm,P0.01,系膜区增宽,足突明显肿胀,部分融合,部分内皮窗孔消失,屏障结构破坏,肾脏间质水肿,有炎细胞浸润;足突融合成片。3H组肾小球、肾小管基底膜明显增厚,分别为(1.88±0.41)μm,(0.96±0.22)μm ,P0.01,足突明显肿胀,大部分融合,部分内皮窗孔消失,屏障结构破坏严重,间质有炎细胞浸润,肾小管上皮细胞有大量脂滴沉积;肾间质可见浆细胞,部分区域有明显髓样结构形成;肾小管刷状缘排列不整齐,微绒毛倒伏;管腔皱缩,局部细胞变性脱落,管壁空洞,足突大部分融合成片,裂孔消失。 2.透射电镜下观察,2H组,晶状体纤维细胞线粒体溶解、断裂、嵴消失,空泡化,细胞质有脂滴沉积。3H组,晶状体纤维细胞间缝隙连接结构破坏,细胞间隙变宽,并有脂滴沉积。扫描电镜下观察,2H组和3H组浅层皮质纤维细胞体积增大,形状、排列紊乱,大范围融合;深层皮质纤维细胞表面不规则;细胞之间的间隙均明显扩大。 3. 2H组出现弥漫性肝细胞脂肪变性,肝小叶内有炎细胞浸润,肝窦周围、汇管区见红染的胶原纤维。3H组发现肝索排列紊乱,肝细胞点状坏死,炎细胞浸润;弥漫性肝细胞脂肪变性,大小不一的脂滴呈弥漫性聚集在肝细胞内,脂褐素沉积。肝细胞间、肝窦周围、汇管区见大量红染的胶原纤维。2H组和3H组透射电镜观察发现肝Kupffer细胞增生,肝细胞胞质内有许多大小不一的脂滴,Disse间隙内胶原纤维多见,有淋巴细胞、浆细胞活化增生,另外,观察到浆细胞和肝星状细胞联系紧密。 结论 1.胰岛素抵抗大鼠血糖正常阶段,肾脏形态学存在病理改变。肾小球滤过屏障,肾小管存在的病理结构改变,可能是形成糖尿病肾病的病理基础。 2.胰岛素抵抗大鼠血糖正常阶段,晶状体的超微结构存在病理结构的改变,有发生白内障的可能性。 3.胰岛素抵抗大鼠血糖正常阶段,肝脏形态学发生早期纤维化现象,可能与免疫系统激活有关。
[Abstract]:Background of study Type 2 diabetes mellitus (T2DM) is a common metabolic endocrine disease, its morbidity, mortality, disability rate and serious harm. Class health. Insulin resistance (IR) is the pathophysiological basis of the pathogenesis of T2DM. The famous" common "The" same soil "theory that diabetes mellitus (DM), hypertension, coronary heart disease, lipid metabolism abnormality, obesity are insulin resistance. in the same soil" Growth ", that is, insulin resistance, is common to these diseases Disease factor. IR refers to insulin that requires more than a physiological amount to produce a birth in the effect organ of insulin The persistent existence of insulin resistance can lead to abnormal glucose tolerance and diabetes. The occurrence of DM is an important cause of end-stage renal disease, blindness and non-invasive amputation, so DM chronic complications seriously affect the quality of life of patients, and give patients, families and society Heavy burden is caused. Previous studies have shown that high sugar high fat (2H) and high sugar high fat (3H) diet have successfully induced an animal model of IR, The lesions have taken place. We speculate that insulin resistance in the early stage of diabetes is normal, and multiple organs have The morphological changes of multiple organs during normal blood glucose were studied on the basis of the successful induction of the animal model of IR rats with high sugar (2H) and high sugar and high fat (3H) diet. Visceral The purpose of this study was to establish a rat model of IR and normal blood glucose, and to observe the kidney of rats. The invention provides an experimental basis for preventing organ injury caused by diabetes, To be sugar A theoretical basis was provided for the treatment of uropathy. The model of IR-resistant rats was successfully made. electrogram The morphological changes of the kidney, the lens and the liver were studied. The results showed that the glomerular and tubular basement membrane of the glomerulus and the renal tubular basement membrane were significantly thickened (2.23 vs 0. 88). m, (0. 86, 0. 25). m and P 0.01 respectively. Swelling, partial fusion, disappearance of partial endothelial window holes, destruction of barrier structure, interstitial edema of kidney, infiltration of inflammatory cells, fusion of feet into pieces. The basement membrane of renal tubular basement membrane was obviously thickened in group 3H group, respectively (1.88% 0. 41). m, (0. 96, 0. 22). m, P0.05). There are obvious swelling, most fusion, disappearance of partial endothelial window hole, destruction of barrier structure, infiltration of inflammatory cells in stroma, large amount of lipid drop deposition in renal tubular epithelial cells, plasmacyplasmacytoma in renal interstitial cells, obvious myeloid structures in some regions, and tubular brush-like structure. The rim arrangement is not neat, the microvilli are lodging, the tube cavity It was observed that the mitochondria were lysed, broken, disappeared, vacuolated, and lipid droplets were deposited in cytoplasm. In 3H group, the gap junction structure was destroyed, the cell gap became wider, and lipid droplets were deposited. The volume of shallow cortical fibroblasts in 2H and 3H groups was observed under scanning electron microscope, and the shape and arrangement were observed. Disorder, large-range fusion; irregular surface of deep cortical cells; clearance between cells was significantly enlarged. There were diffuse hepatocellular fat degeneration in the liver lobules, inflammatory cell infiltration in the hepatic lobule, peripheral blood flow around the liver, and red-stained collagen in the cross-section of the liver. Fiber. 3H group found hepatic cable arrangement disorder, liver cell punctate necrosis, inflammatory fine Cell infiltration; diffuse hepatocellular fat degeneration, diffuse aggregation in hepatocytes, lipofuscin deposition; between hepatocytes, around the liver and around the liver, with a large number of red-stained collagen fibers in the cross-section of the cell; and the transmission electron microscope of 3H group and 3H group showed that the proliferation of the hepatic Kupffer cells was found, and there were many in the cytoplasm of the hepatocytes. Fat drops of different sizes, Disse gap inner glue fibril Vidosee, lymphocytes, plasmacyplasmacyactivations, in addition, observe plasma cells and Conclusion 1. Insulin resistance to normal blood glucose in rats, kidney The pathological changes of glomerular filtration barrier and renal tubules may be the pathological changes of diabetic nephropathy. On the basis of insulin resistance in rats during normal blood glucose, there was a pathological change in the ultrastructure of the lens, and there was a change in the ultrastructure of the lens.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R587.2;R361.2
本文编号：2292943
[Abstract]:Background of study Type 2 diabetes mellitus (T2DM) is a common metabolic endocrine disease, its morbidity, mortality, disability rate and serious harm. Class health. Insulin resistance (IR) is the pathophysiological basis of the pathogenesis of T2DM. The famous" common "The" same soil "theory that diabetes mellitus (DM), hypertension, coronary heart disease, lipid metabolism abnormality, obesity are insulin resistance. in the same soil" Growth ", that is, insulin resistance, is common to these diseases Disease factor. IR refers to insulin that requires more than a physiological amount to produce a birth in the effect organ of insulin The persistent existence of insulin resistance can lead to abnormal glucose tolerance and diabetes. The occurrence of DM is an important cause of end-stage renal disease, blindness and non-invasive amputation, so DM chronic complications seriously affect the quality of life of patients, and give patients, families and society Heavy burden is caused. Previous studies have shown that high sugar high fat (2H) and high sugar high fat (3H) diet have successfully induced an animal model of IR, The lesions have taken place. We speculate that insulin resistance in the early stage of diabetes is normal, and multiple organs have The morphological changes of multiple organs during normal blood glucose were studied on the basis of the successful induction of the animal model of IR rats with high sugar (2H) and high sugar and high fat (3H) diet. Visceral The purpose of this study was to establish a rat model of IR and normal blood glucose, and to observe the kidney of rats. The invention provides an experimental basis for preventing organ injury caused by diabetes, To be sugar A theoretical basis was provided for the treatment of uropathy. The model of IR-resistant rats was successfully made. electrogram The morphological changes of the kidney, the lens and the liver were studied. The results showed that the glomerular and tubular basement membrane of the glomerulus and the renal tubular basement membrane were significantly thickened (2.23 vs 0. 88). m, (0. 86, 0. 25). m and P 0.01 respectively. Swelling, partial fusion, disappearance of partial endothelial window holes, destruction of barrier structure, interstitial edema of kidney, infiltration of inflammatory cells, fusion of feet into pieces. The basement membrane of renal tubular basement membrane was obviously thickened in group 3H group, respectively (1.88% 0. 41). m, (0. 96, 0. 22). m, P0.05). There are obvious swelling, most fusion, disappearance of partial endothelial window hole, destruction of barrier structure, infiltration of inflammatory cells in stroma, large amount of lipid drop deposition in renal tubular epithelial cells, plasmacyplasmacytoma in renal interstitial cells, obvious myeloid structures in some regions, and tubular brush-like structure. The rim arrangement is not neat, the microvilli are lodging, the tube cavity It was observed that the mitochondria were lysed, broken, disappeared, vacuolated, and lipid droplets were deposited in cytoplasm. In 3H group, the gap junction structure was destroyed, the cell gap became wider, and lipid droplets were deposited. The volume of shallow cortical fibroblasts in 2H and 3H groups was observed under scanning electron microscope, and the shape and arrangement were observed. Disorder, large-range fusion; irregular surface of deep cortical cells; clearance between cells was significantly enlarged. There were diffuse hepatocellular fat degeneration in the liver lobules, inflammatory cell infiltration in the hepatic lobule, peripheral blood flow around the liver, and red-stained collagen in the cross-section of the liver. Fiber. 3H group found hepatic cable arrangement disorder, liver cell punctate necrosis, inflammatory fine Cell infiltration; diffuse hepatocellular fat degeneration, diffuse aggregation in hepatocytes, lipofuscin deposition; between hepatocytes, around the liver and around the liver, with a large number of red-stained collagen fibers in the cross-section of the cell; and the transmission electron microscope of 3H group and 3H group showed that the proliferation of the hepatic Kupffer cells was found, and there were many in the cytoplasm of the hepatocytes. Fat drops of different sizes, Disse gap inner glue fibril Vidosee, lymphocytes, plasmacyplasmacyactivations, in addition, observe plasma cells and Conclusion 1. Insulin resistance to normal blood glucose in rats, kidney The pathological changes of glomerular filtration barrier and renal tubules may be the pathological changes of diabetic nephropathy. On the basis of insulin resistance in rats during normal blood glucose, there was a pathological change in the ultrastructure of the lens, and there was a change in the ultrastructure of the lens.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R587.2;R361.2
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相关期刊论文 前4条
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