胰島素抵抗大鼠血糖正常階段多器官形態(tài)學研究
發(fā)布時間：2018-10-25 06:48
【摘要】： 研究背景 2型糖尿病(T2DM)是一種常見的代謝性內分泌疾病,其發(fā)病率、死亡率、致殘率高,嚴重危害人類健康。胰島素抵抗(IR)是T2DM發(fā)病的病理生理基礎。1995年Stern提出了著名的“共同土壤”學說,認為糖尿病(DM)、高血壓、冠心病、脂代謝異常、肥胖是在胰島素抵抗這個共同土壤中“生長”出來的,即胰島素抵抗為這些疾病的共同發(fā)病因素。IR是指需要超過生理量的胰島素才能在胰島素的效應器官產生生理效應。胰島素抵抗持續(xù)存在可導致糖耐量異常和糖尿病的發(fā)生。 DM是引起終末期腎病、失明、非創(chuàng)傷性截肢的重要原因,因此DM慢性并發(fā)癥嚴重影響患者的生活質量,給患者、家屬及社會造成沉重的負擔。我們前期的研究表明,高糖高脂(2H)和高糖高脂高鹽(3H)飲食成功誘導IR大鼠動物模型,在IR發(fā)生后且血糖正常階段,外周神經病變已經發(fā)生。我們推測在糖尿病前期胰島素抵抗血糖正常階段,多種器官已經存在病理改變。因此我們在前期高糖高脂(2H)和高糖高脂高鹽(3H)飲食成功誘導IR大鼠動物模型的基礎上,研究血糖正常時期多臟器的形態(tài)學改變,探討其形態(tài)的變化與糖尿病并發(fā)的臟器損傷的關系。 目的 我們在成功地建立IR且血糖正常的大鼠模型的基礎上,觀察大鼠腎臟、晶狀體及肝臟的形態(tài)結構變化情況。旨在為糖尿病引起的臟器損傷的預防提供實驗基礎,為糖尿病前期的治療提供理論依據(jù)。 方法 成功制作IR抵抗大鼠模型,采用光鏡、透射電鏡、掃描電鏡技術,研究腎臟、晶狀體、肝臟的形態(tài)學變化。 結果 1. 2H組腎小球、腎小管基底膜明顯增厚,分別為(2.23±0.88)μm,(0.86±0.25)μm,P0.01,系膜區(qū)增寬,足突明顯腫脹,部分融合,部分內皮窗孔消失,屏障結構破壞,腎臟間質水腫,有炎細胞浸潤;足突融合成片。3H組腎小球、腎小管基底膜明顯增厚,分別為(1.88±0.41)μm,(0.96±0.22)μm ,P0.01,足突明顯腫脹,大部分融合,部分內皮窗孔消失,屏障結構破壞嚴重,間質有炎細胞浸潤,腎小管上皮細胞有大量脂滴沉積;腎間質可見漿細胞,部分區(qū)域有明顯髓樣結構形成;腎小管刷狀緣排列不整齊,微絨毛倒伏;管腔皺縮,局部細胞變性脫落,管壁空洞,足突大部分融合成片,裂孔消失。 2.透射電鏡下觀察,2H組,晶狀體纖維細胞線粒體溶解、斷裂、嵴消失,空泡化,細胞質有脂滴沉積。3H組,晶狀體纖維細胞間縫隙連接結構破壞,細胞間隙變寬,并有脂滴沉積。掃描電鏡下觀察,2H組和3H組淺層皮質纖維細胞體積增大,形狀、排列紊亂,大范圍融合;深層皮質纖維細胞表面不規(guī)則;細胞之間的間隙均明顯擴大。 3. 2H組出現(xiàn)彌漫性肝細胞脂肪變性,肝小葉內有炎細胞浸潤,肝竇周圍、匯管區(qū)見紅染的膠原纖維。3H組發(fā)現(xiàn)肝索排列紊亂,肝細胞點狀壞死,炎細胞浸潤;彌漫性肝細胞脂肪變性,大小不一的脂滴呈彌漫性聚集在肝細胞內,脂褐素沉積。肝細胞間、肝竇周圍、匯管區(qū)見大量紅染的膠原纖維。2H組和3H組透射電鏡觀察發(fā)現(xiàn)肝Kupffer細胞增生,肝細胞胞質內有許多大小不一的脂滴,Disse間隙內膠原纖維多見,有淋巴細胞、漿細胞活化增生,另外,觀察到漿細胞和肝星狀細胞聯(lián)系緊密。 結論 1.胰島素抵抗大鼠血糖正常階段,腎臟形態(tài)學存在病理改變。腎小球濾過屏障,腎小管存在的病理結構改變,可能是形成糖尿病腎病的病理基礎。 2.胰島素抵抗大鼠血糖正常階段,晶狀體的超微結構存在病理結構的改變,有發(fā)生白內障的可能性。 3.胰島素抵抗大鼠血糖正常階段,肝臟形態(tài)學發(fā)生早期纖維化現(xiàn)象,可能與免疫系統(tǒng)激活有關。
[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.
【學位授予單位】：第四軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2008
【分類號】：R587.2;R361.2
本文編號：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.
【學位授予單位】：第四軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2008
【分類號】：R587.2;R361.2
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