当今社会中，抑郁症已经成为一种十分常见的精神类疾病，甚至会有自残和自杀的倾向和行为，给无数家庭带来沉重的痛苦。抑郁症所涉及的分子机制十分复杂，其病理和生理学的研究尚不清楚。选择性5-羟色胺（5-HT）再摄取抑制剂（Selective Serotonin Reuptake Inhibitor, SSRI）作为近些年来的一种新型药物对抑郁症的治疗有着极大的作用，SSRI类药物由于其对5-HT选择性高、副作用小、依从性好等优点被广泛用于临床治疗。本研究选取SSRI中的氟西汀和帕罗西汀两种药物灌胃健康SD雄性大鼠，分别收取两种药物灌胃前后的尿样，对于收取的尿液进行尿蛋白提取、FASP膜上酶切、酶切产物除盐、LC- MS/MS液相色谱串联质谱分析等实验操作，检测尿液蛋白质组的变化情况。尿液是良好的疾病生物标志物，尿液比血液更快、更灵敏地感受机体的变化。本研究通过对氟西汀和帕罗西汀两组药物灌胃模型的差异蛋白和生物学通路进行分析，并对比两组模型的异同，为抑郁症的早期诊断、SSRI类新药物的研发以及抑郁症副作用的相关研究提供一些可能的线索。

Depression has become a very common mental illness in today's society, and even has the tendency and behavior of self -harm and suicide, which brings heavy pain to countless families. The molecular mechanism involved in depression is very complicated, and the research of pathology and physiology is unclear. As a new type of drug in recent years，Selective Serotonin Reuptake Inhibitor（SSRI）has a great effect on the treatment of depression. Because of the high selectivity, small side effects, and good compliance, SSRIs have been widely used for clinical treatment. This study selects fluoxetine and paroxetine in SSRIs to give healthy SD male rats intragastric administration. We collect the urine samples before and after the intragastric administration of two drugs. For the urine samples, we extract urine protein, use enzyme digestion in the way of FASP, remove the salt ions in the product, analyze with LC- MS/MS to discover the changes in urine protein groups. Urine is a good disease biomarker. Urine feels faster and more sensitive to changes in the body than blood. This study analyzes the differential proteins and biological pathways of fluoxetine and paroxetine's intragastric administration models and compare the similarities and differences between the two models. It provides some possible clues for the early diagnosis of depression, the development of new SSRI drugs and the related research on the side effects of depression.