血管生成素2与内质网应激相关基因在肥胖患者内脏脂肪组织中表达及相关关系的研究  

The expression levels of angiopoietin-2 gene and endoplasmic reticulum stress-related genes in visceral adipose tissue in obese patients and relationship between them

作　　者：何泉[1] 徐盈[1] 唐新华[2] 刘衡[3] 朱宝生[2] 陈雄志[4] 蒋绿芝[5] 

机构地区：[1]云南省第一人民医院急诊科,昆明650032 [2]云南省第一人民医院遗传诊断中心,昆明650032 [3]中国科学院昆明动物所 [4]昆明医科大学第二附属医院肝胆外科 [5]昆明医科大学第二附属医院内分泌科

出　　处：《中国糖尿病杂志》2014年第4期308-312,共5页Chinese Journal of Diabetes

摘　　要：目的探讨肥胖患者内脏脂肪组织中血管生成素2(Ang-2)基因与内质网应激相关基因表达水平及其相关关系。方法选取行胆囊切除术患者204例,以BMI 25kg/m2为切点,分为肥胖(Ob)组及正常体重(Nob)组。ELISA测定Ang-2浓度,稳态模型评估胰岛素抵抗指数(HOMA-IR)。RT-PCR检测脂肪组织中内质网应激相关基因、Ang-2基因和MCP-1mRNA的表达水平。Western blot检测脂肪组织中Ang-2、内质网应激相关基因和MCP-1基因的蛋白表达。结果 (1)Ob组网膜脂肪组织中,内质网应激蛋白相关基因重链结合蛋白(Bip)、肌醇需求蛋白激酶Ⅰ(IREⅠ)、类PKR内质网应激酶(PERK)、氧调节蛋白150(ORP150)、转录激活因子6(ATF6)、X盒结合蛋白1(XBP1)、单核细胞趋化蛋白(MCP-1)及Ang-2的mRNA表达量均高于Nob组(P<0.01);Ob组磷酸化真核翻译起始因子(elF2α)蛋白高于Nob组,但差异无统计学意义[(1.05±0.40)vs(1.10±0.90),P>0.05];(2)PERK和ORP150的表达量与BMI相关;(3)脂肪组织中Ang-2、MCP-1分别与Bip、ORP150、XBP1及IREⅠ表达量有关(P均<0.05)。多因素回归分析显示,Ang-2与内质网应激基因Bip、IREⅠ、PERK、ATF6、ORP150及MCP-1相关;(4)Ang-2和MCP-1在肥胖患者血中及脂肪组织中表达差异无统计学意义(P>0.05)。结论肥胖患者内脏脂肪组织中Ang-2水平升高,内质网应激被激活;Ang-2基因与内质网应激相关基因及MCP-1的表达有关。Objective To study the expression levels of Angiopoietin-2 gene and endoplasmic reticulum stress-related gene in visceral adipose tissue in obese patients,and the relationship of two kinds of genes.Methods Cholecystectomy were carried out in 204 patients and the subjects were divided into obesity （Ob） and normal weight （Nob） group respectively according to BMI〈 or ≥ 25 kg/m2.Insulin resistance index （HOMA-IR） were calculated by homeostasis model assessment method and the concentrations of Angiopoietin-2 were measured by ELISA.RT-PCR and Western blot methods were used for detecting the mRNA and protein expressions of Angiopoietin-2,ER stress-related gene and MCP-1 gene in adipose tissue were measured.Results The mRNA expression levels of ERS-related genes bip （heavy-chain binding protein） expression,inositol demand of protein kinase Ⅰ （IRE Ⅰ）,class PKR ER stress kinase （PERK）,oxygen regulated protein 150 （ORP150）,activating transcription factor 6 （ATF6）,X box binding protein 1 （XBP1）,monocyte chemoattractant protein （MCP-1）,and Angiopoietin-2 were higher in Ob group than in Nob group in omental adipose tissue （P〈0.01）.The phosphorylation of eukaryotic translation initiation factor （elF2α） protein was higher in Ob group than in Nob group but did not reached statistical significance [（1.05 ± 0.40） vs （1.10 ± 0.90）,P〉0.05]; （2） The expressions of PERK and ORP150 were associated with BMI; （3） Angiopoietin-2 and MCP-1 in adipose tissue were related to Bip,ORP150,X box binding protein 1 （XBP1） and IRE Ⅰ expression respectively （P〈 0.05）.Multiple regression analysis showed that Angiopoetin-2 was correlated with endoplasmic reticulum stress-related genes,Bip,IRE Ⅰ,PERK,ATF6,ORP150 and MCP-1.（4） There was no significant difference in Angiopoietin-2 and MCP-1 in obesity patients blood and adipose tissue （P〉0.05）.Conclusion The level of Angiopoietin-2 increases in visceral adipose tissue in obese patients and endoplasmic re

关 键 词：血管生成素-2 内质网应激 脂肪组织 单核细胞趋化蛋白-1 

分 类 号：R589.2[医药卫生—内分泌]