2型糖尿病患者腹腔内脂肪组织中Rev-erbα表达的变化

Expression Change of Rev-erbα in the Intraperitoneal Adipose Tissue of Patients with Type 2 Diabetes

摘要: 研究背景及目的：Rev-erbα是以血红素为生理配体的核受体超家族之一。研究表明，Rev-erbα可调节机体的生物钟节律、糖脂代谢及炎症反应等，从而对生物体多种代谢性疾患及炎症性疾病的发生发展有重要影响。结合Rev-erbα在大鼠脂肪组织中的表达变化，本实验将结合临床研究Rev-erbα在2型糖尿病患者腹腔内脂肪组织中的表达水平，从而进一步探索并证实Rev-erbα对2型糖尿病发生发展的影响。方法：将受试者分为3组：对照组(非超重/肥胖非2型糖尿病)、超重/肥胖组(BMI ≥ 25 kg/m2的非2型糖尿病者)及2型糖尿病组。记录并测量三组受试者的人体学参数和生化学指标，包括性别、年龄、体重指数(BMI)、颈围(NC)、腰围(WC)、臀围(HC)、腰臀比(WHR)、谷丙转氨酶(ALT)、谷草转氨酶(ASL)、肌酐(SCr)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)。通过实时定量PCR (RT-PCR)和Western blot分别检测腹腔内脂肪组织中Rev-erbα的mRNA和蛋白表达水平，并采用ANOVA统计方法分析三组受试者Rev-erbα表达水平的差异。结果：1) 对照组、超重/肥胖组、2型糖尿病组三组受试者一般情况对比结果。三组受试者性别、年龄及ALT、ASL、SCr、HDL-C、LDL-C、TG实验室检查指标对比无明显统计学差异；三组受试者FPG对比，2型糖尿病组明显高于超重/肥胖组及对照组(p < 0.05)；而对照组与超重/肥胖组对比无明显统计学差异；三组受试者BMI、NC、WC、WHR对比，超重/肥胖组明显高于其他两组(p < 0.05)；超重/肥胖组的HC明显高于对照组(p < 0.05)，但与2型糖尿病组对比无明显统计学差异；2型糖尿病组受试者BMI、NC、WC、HC、WHR与对照组对比无明显统计学差异。2) 对照组、超重/肥胖组、2型糖尿病组三组受试者腹腔内脂肪组织中Rev-erbα的mRNA转录水平及蛋白表达水平对比结果。三组受试者对比，2型糖尿病组腹腔内脂肪组织中Rev-erbα的mRNA转录水平明显高于对照组(p < 0.05)，而Rev-erbα的蛋白表达水平也显著高于对照组(p < 0.01)；而对照组和超重/肥胖组之间，以及超重/肥胖组与2型糖尿病组之间mRNA转录水平和Rev-erbα的蛋白表达水平均无明显统计学差异。结论：Rev-erbα在2型糖尿病患者腹腔内脂肪组织中表达增加，提示Rev-erbα可能与2型糖尿病的发生发展相关。

Abstract: Background and Objective: Rev-erbα is one of the nuclear receptor superfamily with heme as its physiologic ligand. Studies reveal that Rev-erbα regulates circadian clock, glucolipid metabolism, inflammatory reaction, etc. Therefore, Rev-erbα has a great impact on the occurrence and develop-ment of various metabolic diseases and inflammatory diseases. Based on the change of expression of Rev-erbα in adipose tissue of rats, this study will combine with clinical to research expression change of Rev-erbα in intraperitoneal adipose tissue of patients with type 2 diabetes, so as to fur-ther explore and prove the influence of Rev-erbα on the occurrence and development of type 2 dia-betes. Methods: Subjects were divided into 3 groups: control group (non-overweight/obese non-type 2 diabetes), overweight/obese group (non-type 2 diabetes with BMI ≥ 25 kg/m2) and type 2 diabetes group. Recording and measuring the three groups of subjects of human learning param-eters and biochemical indexes, including gender, age, body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), alanine aminotrans-ferase (ALT), aspartate aminotransferase (ASL), creatinine (SCr), high-density lipoprotein choles-terol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG). The mRNA and protein expression levels of Rev-erbα in the intraperitoneal adipose tissue were detected by re-al-time quantitative PCR (RT-PCR) and Western blot, and ANOVA statistical method was used to an-alyze the differences in expression levels of Rev-erbα in the three groups. Results: 1) Comparison of the general conditions of the subjects in the control group, the overweight/obese group and the type 2 diabetes group. There was no significant difference in gender, age, ALT, ASL, SCr, HDL-C, LDL-C and TG among the three groups. In the three groups, the FPG of the type 2 diabetes group was sig-nificantly higher than that in the overweight/obese group and in the control group (p < 0.05). There was no statistical difference between the control group and the overweight/obese group. BMI, NC, WC, and WHR were significantly higher in the overweight/obese group than the other two groups (p < 0.05). Though HC is higher in the overweight/obese group than the control group (p < 0.05), there was no significant difference between the overweight/obese group and the type 2 diabetes group. There was no statistically significant difference in BMI, NC, WC, HC and WHR between the type 2 di-abetes group and the control group. 2) Comparison results of mRNA transcription level and protein expression level of Rev-erbα in the intraperitoneal adipose tissue of subjects in the control group, the overweight/obese group and the type 2 diabetes group. The mRNA transcription level of Rev-erbα in the intraperitoneal adipose tissue of the type 2 diabetes group was higher than the control group (p < 0.05), and the protein expression level of Rev-erbα was highest in the type 2 dia-betes group (p < 0.01). However, there was no statistically significant difference in mRNA transcrip-tion and protein levels between the control group and the overweight/obese group, or between the overweight/obese group and the type 2 diabetes group. Conclusion: Rev-erbα is highly expressed in the intraperitoneal adipose tissue of the type 2 diabetes group, which suggests that Rev-erbα may be associated with the occurrence and development of type 2 diabetes.