【摘要】：目的：通過觀察糖尿病認知功能障礙大鼠不同時間、不同部位腦內血腦屏障變化，探討糖尿病認知功能障礙是否與血腦屏障變化有關，以及胰島素的干預效果。 方法：健康成年雄性SD（Sprague-Dawley）大鼠52只，體重180-250g。隨機分為3組：糖尿病組（20只）、胰島素治療組（20只）及對照組（12只），每組均以1、3個月為觀察點。糖尿病組及胰島素治療組大鼠采取單次腹腔注射2%鏈脲佐菌素（Streptozotocin, STZ）誘導糖尿病模型，72小時后尾靜脈取血測定空腹血糖，若空腹血糖11.1mmol/L，且尿糖+++以上者判定為糖尿病造模成功。對照組予單劑量腹腔注射0.1mmol/L檸檬酸-檸檬酸鈉緩沖液（pH4.4），血糖正常。胰島素治療組每日皮下注射低精蛋白鋅胰島素2-3U，使空腹血糖始終處于正常狀態(tài)。于1、3個月分批行Morris水迷宮實驗后處死大鼠，行免疫組化染色，觀察額葉、海馬、基底節(jié)（即尾殼核）及側腦室旁白質區(qū)內皮屏障抗原（Endothelialbarrier antigen, EBA）表達情況。 結果：1、1個月時糖尿病組各腦區(qū)內EBA陽性血管與對照組及胰島素治療組比較，，部分血管出現(xiàn)管壁邊緣硬化、模糊，管腔狹窄、閉塞。各組間血管面積、積分光密度（Integral optical density, IOD）值差異無統(tǒng)計學意義（P0.05）；胰島素治療組與對照組比較，差異無統(tǒng)計學意義（P0.05）。 2、3個月時糖尿病組大鼠各腦區(qū)內EBA陽性血管管壁硬化、模糊，管腔狹窄、閉塞明顯，較1個月時加重，血管面積、IOD值顯著減少，差異有統(tǒng)計學意義（P 0.05）；與對照組比較，差異有統(tǒng)計學意義（P 0.05）。 3、3個月時，胰島素治療組與對照組及1個月胰島素治療組比較，各腦區(qū)內EBA陽性血管面積及IOD值均減少，差異有統(tǒng)計學意義（P 0.05）。 結論：1、血腦屏障損傷是糖尿病認知功能障礙的原因之一，糖尿病認知功能障礙的嚴重程度與血腦屏障損傷的程度相關； 2、胰島素干預可以減輕血腦屏障損傷，但不能阻止其發(fā)生、發(fā)展，血腦屏障的損傷除糖代謝異常外可能有其他因素參與，需進一步探討。
[Abstract]:Aim: to observe the changes of blood-brain barrier (BBB) in the brain of diabetic cognitive dysfunction rats at different time and different sites, and to explore whether diabetes cognitive dysfunction is related to the change of BBB and the effect of insulin intervention. Methods: 52 healthy adult male SD (Sprague-Dawley) rats were weight 180-250 g. They were randomly divided into three groups: diabetic group (n = 20), insulin therapy group (n = 20) and control group (n = 12). Diabetic model was induced by single intraperitoneal injection of 2% streptozotocin (Streptozotocin, STZ) in diabetic group and insulin treatment group. Fasting blood glucose (FBG) was measured by tail vein blood samples 72 hours later. If fasting blood glucose was 11.1 mmol / L, the diabetic model was induced by intraperitoneal injection of 2% streptozotocin (Streptozotocin, STZ). The above-mentioned urine sugar was determined to be a successful model of diabetes mellitus. The control group received a single dose of 0.1mmol/L citric acid-sodium citrate buffer (pH4.4) and normal blood glucose. In insulin treatment group, hypoprotamine zinc insulin 2-3 U was injected subcutaneously daily to keep fasting blood glucose in normal state. The rats were killed by Morris water labyrinth test in batches after 1,3 months, and the expression of (Endothelialbarrier antigen, EBA) of skin barrier antigen in frontal lobe, hippocampus, basal ganglia (caudate putamen nucleus) and paraventricular white matter was observed by immunohistochemical staining. Results: 1. Compared with the control group and the insulin treatment group, some of the EBA positive vessels in the diabetic group showed sclerosing, blurring, narrow and occlusive vascular wall at one month. There was no significant difference in vascular area and integrated optical density (Integral optical density, IOD) between each group (P0.05); there was no significant difference between insulin treatment group and control group (P0.05). At 2 and 3 months, the EBA positive vascular wall in the diabetic group was sclerosing and blurred, the lumen was narrow and occlusive, which was more serious than that at 1 month, and the area of blood vessel and the IOD value were significantly decreased (P < 0. 05). Compared with the control group, the difference was statistically significant (P 0.05). At 3 and 3 months, compared with the control group and the 1 month insulin treatment group, the area of EBA positive vessels and the value of IOD in each brain region decreased significantly in the insulin treatment group (P 0.05). Conclusion: 1. The blood-brain barrier injury is one of the causes of diabetes cognitive dysfunction. The severity of diabetes cognitive dysfunction is related to the degree of blood-brain barrier damage. 2, insulin intervention can reduce the blood-brain barrier injury, but can not prevent its occurrence and development, the blood-brain barrier injury may have other factors except abnormal glucose metabolism, need to be further explored.
【學位授予單位】：大連醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R587.1;R749.2

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