【摘要】：目的：探討實驗性糖尿病大鼠坐骨神經(jīng)微血管通透性變化與周圍神經(jīng)病變的相關性。 方法：將雄性SD大鼠(22020g)隨機分成實驗組（T組，n=60）和對照組（N組，n=12）。采用腹腔注射鏈脲菌素(STZ)的方法將實驗組的60只大鼠全部制備成實驗性1型糖尿病大鼠模型。在成模即刻(0w)、成模后2w、4w、8w、12w分別隨機選取12只大鼠,分別用T0、T2、T4、T8、T12表示，依次通過伊文思蘭灌注在分光光度計下測坐骨神經(jīng)組織OD值和熒光顯微鏡下測其熒光量以及坐骨神經(jīng)的含水量等指標來了解坐骨神經(jīng)滋養(yǎng)血管的通透性。對其坐骨神經(jīng)傳導速度進行檢測，觀察大鼠成模后不同時間的病理改變,包括其HE染色及電鏡下的超微結構變化。并對坐骨神經(jīng)組織含水量與NCV、組織EB含量與NCV進行線性相關分析。用免疫組化的方法檢測血管內(nèi)皮生長因子（VEGF）在大鼠坐骨神經(jīng)上的表達。 結果：1.糖尿病大鼠伊文思藍灌注后，，分光光度計下其坐骨神經(jīng)OD值從4W開始明顯增加（p0.05）；熒光顯微鏡下觀察坐骨神經(jīng)組織的熒光量可見T4、T8、T12的大鼠神經(jīng)外膜血管管壁非常強的紅色熒光，神經(jīng)內(nèi)膜、神經(jīng)束呈現(xiàn)較強的紅色熒光。而與正常對照組相比，糖尿病大鼠8W、12W始出現(xiàn)坐骨神經(jīng)組織含水量明顯增加。2.與正常對照組相比，糖尿病組大鼠從2W開始出現(xiàn)坐骨神經(jīng)傳導速度（Nerveconduction velocity；NCV）明顯下降（p0.05）。光鏡下可見，糖尿病大鼠的坐骨神經(jīng)從4w開始出現(xiàn)神經(jīng)纖維的髓鞘變薄、形態(tài)不規(guī)則,軸突染色變淺，并伴有軸索萎縮；電鏡下觀察大鼠坐骨神經(jīng)的變化可見，T4、T8、T12的糖尿病大鼠均出現(xiàn)了有髓神經(jīng)纖維髓鞘板層薄厚不一、分離或脫落，局限增厚，結構疏松，且隨糖尿病病程的推移，坐骨神經(jīng)結構病變逐漸加重。3.通過對坐骨神經(jīng)組織含水量與NCV、組織EB含量與NCV進行線性相關分析，結果顯示，在糖尿病的病程中，坐骨神經(jīng)組織含水量與NCV存在負相關（r=-0.903）；坐骨神經(jīng)組織EB含量與NCV呈負相關關系（r=-0.799）。4. VEGF在各組大鼠坐骨神經(jīng)上的表達顯示T2、T4、T8的糖尿病大鼠的坐骨神經(jīng)纖維雪旺氏細胞、軸突以及髓鞘中表達呈陽性，血管壁陽性表達增強。T12糖尿病大鼠的坐骨神經(jīng)纖維雪旺氏細胞表達呈陽性,而軸索、髓鞘無表達，血管壁表達稍弱，這與N組、T0大鼠類似。 結論：1.糖尿病大鼠成模后4周發(fā)生了微血管通透性的改變。2.糖尿病大鼠成模后2周出現(xiàn)坐骨神經(jīng)功能的改變；糖尿病大鼠成模后4周出現(xiàn)坐骨神經(jīng)結構的改變。3.實驗性1型糖尿病大鼠坐骨神經(jīng)微血管通透性的改變是與坐骨神經(jīng)結構、功能的變化相關的。4.微血管通透性與坐骨神經(jīng)病變有相關關系，其可能機制之一是糖尿病誘導血管內(nèi)皮生長因子VEGF的表達。
[Abstract]:Aim: to investigate the relationship between microvascular permeability of sciatic nerve and peripheral neuropathy in experimental diabetic rats. Methods: male SD rats (22020g) were randomly divided into experimental group (group T) and control group (group N). The experimental model of type 1 diabetes was established by intraperitoneal injection of streptozotocin (STZ) in 60 experimental rats. At 0 w, 12 rats were randomly selected for 2 weeks, 4 weeks, 8 weeks and 12 weeks, respectively. The rats were represented by T0 T2T2OT4T4T8 T12, respectively. In order to understand the permeability of sciatic nerve nourishing vessels, OD value of sciatic nerve was measured with spectrophotometer, fluorescence quantity of sciatic nerve and water content of sciatic nerve were measured under fluorescence microscope. The conduction velocity of sciatic nerve was measured to observe the pathological changes of rat model at different time, including HE staining and ultrastructural changes under electron microscope. The correlation between water content of sciatic nerve tissue and NCVand EB content and NCV were analyzed. The expression of vascular endothelial growth factor (VEGF) in sciatic nerve of rats was detected by immunohistochemical method. The result is 1: 1. The OD value of sciatic nerve in diabetic rats increased significantly from 4W to 4W after perfusing Evans blue (p0.05), and the fluorescence amount of sciatic nerve tissue was observed under fluorescence microscope. The nerve bundle showed a strong red fluorescence in the inner part of the nerve. Compared with the normal control group, the water content of sciatic nerve tissue in diabetic rats increased significantly at 8W and 12W. Compared with the normal control group, the Nerveconduction conduction velocity (nCV) of the diabetic rats decreased significantly from 2 W (p0.05). Under the light microscope, the sciatic nerve of diabetic rats appeared the myelin sheath thinning, the shape irregular, the axon staining shallower and the axonal atrophy from 4 weeks. Observing the changes of sciatic nerve under electron microscope, we can see that the myelin lamellar layer of myelinated nerve fibers in diabetic rats with T4 and T8 and T12 were different in thickness, separated or shed, localized thickening, loose structure, and with the course of diabetes. The pathological changes of sciatic nerve structure gradually aggravation. A linear correlation analysis was made between water content of sciatic nerve tissue and NCV. The results showed that there was a negative correlation between water content of sciatic nerve tissue and NCV in the course of diabetes mellitus (r-0.903). There was a negative correlation between EB content and NCV in sciatic nerve tissue (r-0.799) .4. The expression of VEGF in sciatic nerve showed positive expression in sciatic nerve fiber Schwann cells, axons and myelin sheath of diabetic rats. The expression of Schwann cells in sciatic nerve fibers of T12 diabetic rats was enhanced, but no expression of axonal and myelin sheath was found, and the expression of vascular wall was slightly weak, which was similar to that of T0 rats in N group. Conclusion 1. The change of microvascular permeability occurred 4 weeks after diabetic rat model. 2. 2. The changes of sciatic nerve function were observed in diabetic rats 2 weeks after model formation, and 3. 3 in diabetic rats 4 weeks after model formation. The change of microvascular permeability of sciatic nerve in experimental type 1 diabetic rats is related to the changes of structure and function of sciatic nerve. Microvascular permeability is related to sciatic neuropathy, and one of its possible mechanisms is the expression of vascular endothelial growth factor (VEGF) induced by diabetes.
【學位授予單位】：遵義醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R587.2;R741

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