帕金森病大鼠肠功能障碍及血清脑肠肽与脑内酪氨酸羟化酶相关性研究
发布时间：2018-12-25 08:31
【摘要】：目的:观察鱼藤酮诱导的PD大鼠行为学改变及胃肠功能障碍,测定血清中胆囊收缩素(CCK)、新脂肪因子(Nesfatin-1)含量与黑质纹状体中酪氨酸羟化酶(TH)平均光密度值的相关性来研究脑肠肽是否可作为PD早期诊断指标;测定不同时间不同部位TH平均光密度值的变化来探讨PD早期可能的发病机制。方法:采用随机原则将84只大鼠分成实验组及溶媒组各42只,实验组采用颈背部皮下注射浓度为2mg/ml的鱼藤酮葵花油乳液,溶媒组注射等体积葵花油乳液,分别在0周、2周、4周、6周注射30分钟后测定大鼠体重、跨步实验及悬挂实验、粪便含水量百分比及胃内容物占体重的百分比,利用免疫组化法检测不同时期直肠、胸髓及黑质纹状体酪氨酸羟化酶(TH)平均光密度值,ELISA法测定脑肠肽CCK及Nesfatin-1的含量,应用Pearson分析法分别分析血清中CCK、Nesfatin-1与脑内TH之间的关系。结果:行为学检测发现,较溶媒组相比,实验组大鼠体重显著下降(P0.05);实验组悬挂实验的分值明显降低(P0.05),尤其在2~4周最明显,而从4~6周后则下降的程度变慢,实验组大鼠跨步数目明显减少(P0.05),而溶媒组大鼠体重、悬挂实验及跨步实验均无明显变化(P0.05)。粪便含水量及胃内容物占体重百分比测定发现,实验组从第2周开始即出现粪便含水量显著减少(P0.05)及胃内容物占体重的百分比明显增高(P0.05)。应用ELISA法检测发现,与溶媒组相比,实验组大鼠血清中CCK含量及Nesfatin-1含量从第2周开始就明显增高(P0.05),Nesfatin-1含量在第6周后逐渐出现下降趋势;溶媒组大鼠均无明显变化(P0.05)。免疫组化结果显示,实验组直肠、胸髓及黑质纹状体中TH平均光密度值明显下降(P0.05),直肠从第2周开始就表现出较明显的下降趋势;而溶媒组大鼠肠道、胸髓及黑质纹状体中TH平均光密度值无明显改变(P0.05)。从实验组大鼠血清CCK含量与脑内TH平均光密度值两者的动态变化发现两者随时间变化呈负相关性r=-0.953(P0.05)。实验组大鼠血清中Nesfatin-1含量与黑质纹状体中TH平均光密度值无明显相关性r=-0.530(P0.05)。结论:帕金森病大鼠血清中CCK含量早期明显升高,其与脑内多巴胺能神经元呈负相关性,提示血清中CCK可作为预测早期PD的可能指标。
[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.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R742.5
本文编号：2390934
[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.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R742.5
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