慢性应激诱导DPP-4表达及对脂肪炎症和代谢的影响

目的　分析慢性应激诱导脂肪二肽基肽酶-4（DPP-4）表达及对脂肪炎症和糖代谢的影响。 方法　雄性SPF级小鼠20只随机分慢性应激（Stress）组和正常对照（Control）组。Stress组小鼠每天在自制式束缚器中限制活动2 h,实验持续14 d。采用免疫组化方法检测巨噬细胞表面标志物（CD11b）在脂肪中的表达,实时定量PCR法检测脂肪组织中DPP-4、细胞因子（Adiponectin、MCP-1、IL-6、TNF-α）及糖代谢（IRS-1、GLUT-4）等指标的mRNA的相对表达量;ELISA法检测DPP-4酶活性及GLP-1浓度。 结果　Stress小鼠腹部白色脂肪组织（WAT）与Control组相比显著的退缩及其重量显著降低（P<0.001）。Stress组WAT出现大量的单核细胞、中性粒细胞浸润反应和炎症性改变;Stress显著降低Adiponectin的表达,并显著增高MCP-1、IL-6、TNF-α的mRNA表达及其血液中的浓度（P<0.001）;Stress组WAT组织中DPP-4 mRNA表达及其血液中的活性显著增高,而GLP-1血液中的浓度显著降低（P<0.001）;Stress组WAT组织中IRS-1及GLUT-4的mRNA水平显著低于Control组（P<0.001）。 结论　慢性应激诱导脂肪DPP-4异常表达,进而引起脂肪炎症和糖代谢异常等反应。

The chronic stress induced expression of DPP-4 and its role in adipose inflammation and glucose metabolism

Objective　To analyze chronic stress induced dipeptidyl peptidase-4 (DPP-4) expression and its role in adipose inflammation and glycometabolism.　Methods　20 male SPF mice were randomly divided into two groups: a stress group and a control group. Mice in the stress group were restrained in our own restraint device for 2 hours per day and lasted for 14 days. The expression of macrophage surface marker (CD11b) in adipose tissue was detected by immunohistochemistry. The expression of DPP-4, adipocytokines (Adiponectin, MCP-1, IL-6, TNF-α) in adipose tissue and the expressions of glucose metabolism molecules (IRS-1, GLUT-4) were further detected by RT-PCR. The enzymatic activity of DPP-4 and the concentration of GLP-1 were detected by ELISA.　Results　The white adipose tissue (WAT) of the stress group mice significantly retracted and WAT weight significantly reduced (P<0.001). WAT in the stress group showed a large number of monocytes, neutrophils infiltration and inflammatory changes. Mice in the stress group significantly decreased the expression of Adiponectin and significantly increased the expression of MCP-1, IL-6 and TNF-α (P<0.001). DPP-4 expression in WAT tissues and its activity in blood increased significantly in the stress group, but the concentration of serum GLP-1 decreased significantly (P<0.001). The mRNA level of IRS-1 and mRNA level of GLUT-4 in WAT of the stress group were significantly lower than that of the control group (P<0.001). Conclusions　Chronic stress induced abnormal expression of DPP-4 in adipose tissue, which can lead to adipose inflammation and abnormal glycometabolism.