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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 investigate the expression of angiopoietin 2 (Ang-2) gene and ER stress-related genes in visceral adipose tissue of obese patients. Methods Totally 204 patients undergoing cholecystectomy were divided into Ob group and Nob group with BMI 25kg / m2 as the cut-off point. The concentration of Ang-2 was measured by ELISA, and the homeostasis model was used to assess the insulin resistance index (HOMA-IR). RT-PCR was used to detect the expression of ER stress-related genes, Ang-2 mRNA and MCP-1 mRNA in adipose tissue. Western blot was used to detect the protein expression of Ang-2, ER stress-related genes and MCP-1 in adipose tissue. Results (1) In the omental adipose tissue of Ob, the endoplasmic reticulum stress protein related gene heavy chain binding protein (Bip), inositol-requiring protein kinase Ⅰ (IREⅠ), PKR-like endoplasmic reticulum- The mRNA expression of ORP150, ATF6, XBP1, MCP-1 and Ang-2 were significantly higher than those in Nob group (P (P <0.05); (2) The expression of phosphorylated eIF2α in Ob group was significantly higher than that in Nob group ([1.05 ± 0.40 vs 1.10 ± 0.90, P> 0.05] The expression of PERK and ORP150 correlated with BMI. (3) The expressions of Ang-2 and MCP-1 in adipose tissue were correlated with the expression of Bip, ORP150, XBP1 and IREⅠ (P all <0.05). Multivariate regression analysis showed that Ang-2 was associated with endoplasmic reticulum stress genes Bip, IREⅠ, PERK, ATF6, ORP150 and MCP-1. (4) Ang-2 and MCP-1 in blood and adipose tissue of obese patients The difference was not statistically significant (P> 0.05). CONCLUSIONS: Ang-2 levels are elevated in visceral adipose tissue and endoplasmic reticulum stress is activated in obese patients. Ang-2 gene is associated with the expression of stress-related genes and MCP-1 in endoplasmic reticulum.