【摘要】：目的:觀察魚藤酮誘導的PD大鼠行為學改變及胃腸功能障礙,測定血清中膽囊收縮素(CCK)、新脂肪因子(Nesfatin-1)含量與黑質(zhì)紋狀體中酪氨酸羥化酶(TH)平均光密度值的相關(guān)性來研究腦腸肽是否可作為PD早期診斷指標;測定不同時間不同部位TH平均光密度值的變化來探討PD早期可能的發(fā)病機制。方法:采用隨機原則將84只大鼠分成實驗組及溶媒組各42只,實驗組采用頸背部皮下注射濃度為2mg/ml的魚藤酮葵花油乳液,溶媒組注射等體積葵花油乳液,分別在0周、2周、4周、6周注射30分鐘后測定大鼠體重、跨步實驗及懸掛實驗、糞便含水量百分比及胃內(nèi)容物占體重的百分比,利用免疫組化法檢測不同時期直腸、胸髓及黑質(zhì)紋狀體酪氨酸羥化酶(TH)平均光密度值,ELISA法測定腦腸肽CCK及Nesfatin-1的含量,應用Pearson分析法分別分析血清中CCK、Nesfatin-1與腦內(nèi)TH之間的關(guān)系。結(jié)果:行為學檢測發(fā)現(xiàn),較溶媒組相比,實驗組大鼠體重顯著下降(P0.05);實驗組懸掛實驗的分值明顯降低(P0.05),尤其在2~4周最明顯,而從4~6周后則下降的程度變慢,實驗組大鼠跨步數(shù)目明顯減少(P0.05),而溶媒組大鼠體重、懸掛實驗及跨步實驗均無明顯變化(P0.05)。糞便含水量及胃內(nèi)容物占體重百分比測定發(fā)現(xiàn),實驗組從第2周開始即出現(xiàn)糞便含水量顯著減少(P0.05)及胃內(nèi)容物占體重的百分比明顯增高(P0.05)。應用ELISA法檢測發(fā)現(xiàn),與溶媒組相比,實驗組大鼠血清中CCK含量及Nesfatin-1含量從第2周開始就明顯增高(P0.05),Nesfatin-1含量在第6周后逐漸出現(xiàn)下降趨勢;溶媒組大鼠均無明顯變化(P0.05)。免疫組化結(jié)果顯示,實驗組直腸、胸髓及黑質(zhì)紋狀體中TH平均光密度值明顯下降(P0.05),直腸從第2周開始就表現(xiàn)出較明顯的下降趨勢;而溶媒組大鼠腸道、胸髓及黑質(zhì)紋狀體中TH平均光密度值無明顯改變(P0.05)。從實驗組大鼠血清CCK含量與腦內(nèi)TH平均光密度值兩者的動態(tài)變化發(fā)現(xiàn)兩者隨時間變化呈負相關(guān)性r=-0.953(P0.05)。實驗組大鼠血清中Nesfatin-1含量與黑質(zhì)紋狀體中TH平均光密度值無明顯相關(guān)性r=-0.530(P0.05)。結(jié)論:帕金森病大鼠血清中CCK含量早期明顯升高,其與腦內(nèi)多巴胺能神經(jīng)元呈負相關(guān)性,提示血清中CCK可作為預測早期PD的可能指標。
[Abstract]:Objective: to observe the behavioral changes and gastrointestinal dysfunction in PD rats induced by rotenone, and to determine the cholecystokinin (CCK), in serum. The correlation between the content of new fat factor (Nesfatin-1) and the average optical density of tyrosine hydroxylase (TH) in nigra striatum to study whether brain intestinal peptide can be used as an early diagnostic index of PD. The changes of average optical density of TH at different time and different sites were measured to explore the early pathogenesis of PD. Methods: 84 rats were randomly divided into experimental group (n = 42) and solvent group (n = 42). The experimental group was injected with rotenone sunflower oil emulsion (2mg/ml) subcutaneously, and the solvent group was injected with the same volume sunflower oil emulsion for 0 weeks. The rats' body weight, step test and suspension test, the percentage of fecal water content and the percentage of gastric contents in body weight were measured by immunohistochemical method after 30 minutes of injection for 2 weeks, 4 weeks and 6 weeks. The mean optical density of tyrosine hydroxylase (TH) in thoracic spinal cord and nigra striatum was measured by ELISA. The contents of CCK and Nesfatin-1 in brain intestine were determined by ELISA method. The relationship between serum CCK,Nesfatin-1 and TH in brain was analyzed by Pearson assay. Results: the behavior test showed that the weight of the experimental group was significantly lower than that of the solvent group (P0.05). The scores of suspension test in the experimental group were significantly decreased (P0.05), especially in the 4th week of the experiment group, but the degree of the decrease was slower after 4 weeks. The number of stride in the experimental group was significantly decreased (P0.05), while the weight of the rats in the solvent group was significantly decreased (P0.05), and the weight of the rats in the solvent group was significantly lower than that in the control group. There was no significant change in suspension test and step test (P0.05). The percentage of fecal water content and gastric contents in body weight was significantly decreased (P0.05) and the percentage of gastric contents in body weight was significantly increased (P0.05) in the experimental group from the second week. Compared with the solvent group, the content of CCK and Nesfatin-1 in the serum of the experimental group increased significantly from the second week (P0.05), and the content of Nesfatin-1 decreased gradually after 6 weeks. No significant change was found in the solvent group (P0.05). The results of immunohistochemistry showed that the average optical density of TH in rectum, thoracic pulp and striatum of nigra decreased significantly in the experimental group (P0.05), and the rectum showed a more obvious downward trend from the second week. However, the mean optical density of TH in the intestinal tract, thoracic spinal cord and substantia nigra was not significantly changed in the solvent group (P0.05). From the dynamic changes of serum CCK content and TH optical density in the brain of experimental rats, it was found that there was a negative correlation between the two changes with time (P0.05). There was no significant correlation between the content of Nesfatin-1 in serum and the average optical density of TH in nigra striatum in the experimental group (P0.05). Conclusion: the level of CCK in serum of Parkinson's disease rats was significantly increased at the early stage, which was negatively correlated with dopaminergic neurons in the brain, suggesting that serum CCK may be used as a predictor of early PD.
【學位授予單位】：南華大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R742.5

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