【作者】 孙敏；

【导师】 王越晖；

【作者基本信息】 吉林大学 ， 临床医学， 2014， 硕士

【摘要】 背景：冠心病是目前多发的心血管疾病之一，常合并多种并发症。糖尿病既是其高危因素，也是其常见的并发症。我国糖尿病患者人数已居世界首位，冠心病是目前糖尿病患者最常见的死亡原因之一，因此，在冠心病患者中加强对糖代谢异常的筛查及对血糖的合理干预对改善患者预后有重要意义。巨噬细胞移动抑制因子(macrophage migration inhibitory factor，MIF)是一种多效的细胞因子，是机体免疫和炎症反应重要的介质，在冠心病及糖尿病的发生发展中发挥了重要作用。探讨MIF在冠心病合并糖尿病中的作用将有助于阐明MIF在其发病中的机制，并作为干预靶点进行有效的预防及治疗。二肽基肽酶-4（dipeptidyl peptidase4，DPP-4）是一种多功能的蛋白水解酶，广泛存在于血浆、肾脏、胃肠道、淋巴结和结缔组织等体内组织中。由于其在体内可以分解胰高血糖素样肽-1(Glucagon-like peptide-1，GLP-1)，因此成为2型糖尿病治疗的新靶点。DPP-4抑制剂作为新型的口服降糖药渐渐成为人们的关注焦点，近年来，随着该类药物的广泛应用，越来越多的研究关注其降糖外其他优势。目的：本课题通过检测冠心病患者，合并糖尿病的冠心病患者，及经DPP-4抑制剂治疗3个月的合并糖尿病的冠心病患者外周血血清中巨噬细胞移动抑制因子浓度的变化，探讨MIF在冠心病合并糖尿病中的作用，明确DPP-4抑制剂对合并糖尿病的冠心病患者降糖的同时通过调节MIF的变化发挥的降糖外效应。方法：选择2013年02月至2014年01月在本院心血管内科住院患者60例（男27例，女33例）。分为3组：冠心病组，冠心病合并糖尿病组，规律口服沙格列汀3个月后的冠心病合并糖尿病组。通过对体重指数（BMI）、谷丙转氨酶(ALT)、谷草转氨酶(AST)、肌酐(Cr)、尿素氮(BUN)、糖化血红蛋白（HbA1c）、甘油三酯（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、总胆固醇（TC）的检测，应用酶联免疫吸附试验（Enzyme-linked immunosorbent assay, ELISA）法，检测3组血清的MIF水平，进行统计学分析。实验数据均数±标准差（x s）表示用于计量资料。两组间计量资料的比较采用均数t检验。用SPSS19.0统计软件进行分析。P<0.05，具有统计学意义。结果：1.冠心病合并糖尿病组血清MIF水平明显高于单纯冠心病组血清MIF水平，有显著统计学差异(P<0.05)。2.冠心病合并糖尿病患者应用DPP-4抑制剂后血清MIF水平显著下降，有显著统计学差异(P<0.05)。结论：1.MIF在合并糖尿病的冠心病中发挥了重要作用，MIF可能是高血糖加速冠心病的重要致病因素之一。2.DPP-4抑制剂能有效降低血糖并抑制血清MIF水平，DPP-4抑制剂在降糖的同时可能通过降低MIF发挥抗炎作用进而发挥冠心病的保护作用。更多还原

【Abstract】 Background:Coronary heart disease is one of the major cardiovascular diseases,which is often associated with a variety of complications. Diabetes is one of its riskfactors, but also its common complications. The number of diabetic patients in Chinaranks first in the world. Coronary heart disease is the most common cause of death indiabetic patients, therefore, it is very important to strengthen screening abnormalglucose metabolism of glucose and reasonable intervention to improve the prognosisof patients with coronary artery disease. Macrophage migration inhibitory factor thatis a pleiotropic cytokine and an important media of immune and inflammatoryresponses，plays an important role in the development of coronary heart disease anddiabetes. Exploring the effect of macrophage migration inhibitory factor on coronaryheart disease companying with diabetes will help to clarify the role of MIF in thepathogenesis mechanisms, and it can be interventional target for the effectivetreatments.Dipeptidyl peptidase4widely presents in the plasma, kidneys, gastrointestinaltracts, lymphatic tissues and other tissues in vivo, that is a multifunctional proteolyticenzyme. It is a new target for the treatment of type2diabetes since dipeptidylpeptidase4may decompose some protein just like Glucagon-like peptide-1. DPP-4inhibitors acts as a novel oral hypoglycemic agents, which gradually become the hotpoint in recent years. With the extensive use of these drugs, more and moreadvantages except its hypoglycemic role in research have been paid close attention.Objective:We detected the concentration of MIF that exposed in peripheral bloodserum in the patients with coronary heart disease, coronary artery disease withdiabetes, coronary artery disease with diabetes after three months of treatment byDPP-4inhibitors. We tried to explore the role of MIF in coronary heart disease withdiabetes, and to clarify DPP-4inhibitors’ other effects besides lowering blood sugarconcentration in diabetic patients with coronary heart disease by adjusting the MIFconcentration. Methods:60patients Hospitalized in the department of Cardiology in the secondhospital of Jilin University from February2013to January2014(27males，33females)were selected，they were divided into3groups, coronary heart disease group(CHD),coronary heart disease with diabetes group，coronary heart disease with diabetesgroup at the3months after treatment by DPP-4inhibitors, each group included30patients. Each patient’s body mass index, glutamic-pyruvic transaminases,glutamic-oxaloacetic transaminase, glycosylated hemoglobin, riglycerides, lowdensity lipoprotein，high density lipoprotein are detected. The MIF serum levels ofeach group are examined by enzyme-linked immunosorbent assay method, statisticalanalysis was used to analyzed the determination of the test results. All the data wereexpressed as means±SD. The differences between two groups were analyzed by t-test.All statistical analysis was performed using SPSS19.0software and P<0.05wasstatistically significant.Results:1.Compared with coronary heart disease group，the MIF concentration incoronary heart disease with diabetes group increased，difference was statisticallysignificant (P <0.05).2.The MIF concentration in coronary heart disease with diabetes group weresignificantly decreased after the treatment by DPP-4inhibitors，difference wasstatistically significant (P <0.05).Conclusion:1.The MIF plays an important role in coronary heart disease with diabetes，and itmay be an important factor in progressing of high blood glucose acceleratingcoronary artery disease.2.DPP-4inhibitor can effectively reduce blood glucose levels and decrease theMIF concentration， they may exert anti-inflammatory effects hypoglycemicsimultaneously by reducing the MIF concentration.更多还原