白细胞介素-22在多囊卵巢综合征大鼠胰岛素抵抗中的作用机制  

Mechanism of interleukin-22 regulating insulin resistance in polycystic ovary syndrome rats

作　　者：马晓晨 祁玉娟[2] 刘颖[2] 孙芳 严晓南[2] 张蓓 Ma Xiaochen;Qi Yujuan;Liu Ying;Sun Fang;Yan Xiaonan;Zhang Bei(Xuzhou Clinical School of Xuzhou Medical University,Xuzhou 221009,China;Clinical Center of Reproductive Medicine,Xuzhou Central Hospital,Xuzhou 221009,China;Department of Obstetrics and Gynecology,Xuzhou Clinical School of Xuzhou Medical University,Xuzhou 221009,China)

机构地区：[1]徐州医科大学徐州临床学院,徐州221009 [2]徐州市中心医院生殖医学中心,徐州221009 [3]徐州医科大学徐州临床学院妇产科,徐州221009

出　　处：《中华生殖与避孕杂志》2023年第2期184-190,共7页Chinese Journal of Reproduction and Contraception

基　　金：国家自然科学基金(81571405);江苏省自然科学基金(BK20161169)。

摘　　要：目的研究胰腺白细胞介素-22(interleukin-22,IL-22)信号通路在多囊卵巢综合征(polycystic ovary syndrome,PCOS)大鼠胰岛素抵抗(insulin resistance,IR)中的作用机制。方法选取21 d的SD大鼠按照计算机随机生成数字的方式分为对照组和PCOS组,每组各10只。PCOS组大鼠皮下埋置双氢睾酮(dihydrotestosterone,DHT)硅胶缓释管90 d。测定大鼠体质量,检测腹腔葡萄糖耐量试验(intraperitoneal glucose tolerance test,IPGTT)、胰岛素耐量试验(intraperitoneal insulin tolerance test,IPITT),酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清IL-22和空腹胰岛素(fasting insulin,FINS),计算胰岛素稳态指数(homeostasis model assessment of insulin resistance,HOMA-IR),免疫荧光染色观察胰岛β细胞中IL-22受体1(interleukin-22 receptor 1,IL-22R1)的定位与差异性表达,蛋白印迹法检测大鼠胰腺组织IL-22、酪氨酸蛋白激酶1(Janus kinase 1,JAK1)、信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)蛋白表达水平。结果PCOS组体质量[(420.50+10.26)g]明显高于对照组[(314.40+6.54)g,P=0.003],血清IL-22浓度[(9.86±1.41)ng/L]低于对照组[(16.07±4.68)ng/L,P=0.038],PCOS组FINS[(17.97±2.86)mU/L]、HOMA-IR(4.46±0.80)明显高于对照组[(13.05±2.12)mU/L,P=0.001;2.99±0.61,P=0.001]。PCOS组IPGTT 30 min、60 min、90 min血糖[(15.58±1.86)mmol/L、(10.71±2.07)mmol/L、(7.47±1.36)mmol/L]均明显高于对照组[(12.54±1.60)mmol/L,P=0.010;(8.33±1.02)mmol/L,P=0.026;(6.28±0.72)mmol/L,P=0.013];PCOS组的糖耐量曲线下面积[area under curve,AUC;(1248.71±164.23)mmol/(L·min)]明显大于对照组[(1007.29±102.29)mmol/(L·min),P=0.010]。PCOS组IPITT 60 min、90 min、120 min血糖[(3.12±0.28)mmol/L、(2.62±0.17)mmol/L、(2.28±0.25)mmol/L]均明显高于对照组[(2.60±0.28)mmol/L,P=0.031;(2.10±0.33)mmol/L,P=0.026;(1.90±0.24)mmol/L,P=0.033];PCOS组胰岛素耐量AUC[(414.60±23.06)mmol/(L·min)]明显大于对照组[(359.40±39.95)mmoObjective To evaluate the mechanism of pancreatic interleukin-22(IL-22)signaling pathway regulating insulin resistance(IR)in polycystic ovary syndrome(PCOS)rats.Methods Postnatal 21 d SD rats were divided into control group and PCOS group with 10 rats in each group based on numbers randomly generated by computer.PCOS rats implanted with a silastic tube filled with dihydrotestosterone(DHT)at dosage of 7.5 mg.Their body weight was monitored weekly.At the end of the experiment,the intraperitoneal glucose tolerance test(IPGTT)and intraperitoneal insulin test(IPITT)were conducted,the serum IL-22 and fasting insulin(FINS)were monitored through the enzyme-linked immunosorbent assay(ELISA),and homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The location and differential expression of the interleukin-22 receptor 1(IL-22R1)in pancreatic β cells were observed by immunofluorescence staining,and the expressions of the IL-22,Janus kinase 1(JAK1),signal transducer and activator of transcription 3(STAT3)proteins were detected by Western blotting.Results Compared with control group,the body weight was increased[(420.50±10.26)g vs.(314.40±6.54)g,P=0.003]and the serum level of IL-22 in PCOS group was decreased[(9.86±1.41)ng/L vs.(16.07±4.68)ng/L,P=0.038].The levels of FINS and HOMA-IR were higher in PCOS group than in control group[(17.97±2.86)mU/L vs.(13.05±2.12)mU/L,P=0.001;4.46±0.80 vs.2.99±0.61,P=0.001].The glucose levels in IPGTT test were significantly elevated in PCOS group in 30 min,60 min and 90 min compared with control group[(15.58±1.86)mmol/L vs.(12.54±1.60)mmol/L,P=0.010;(10.71±2.07)mmol/L vs.(8.33±1.02)mmol/L,P=0.026;(7.47±1.36)mmol/L vs.(6.28±0.72)mmol/L,P=0.013],as well as the area under curve(AUC)[(1248.71±164.23)mmol/(L·min)vs.(1007.29±102.29)mmol/(L·min),P=0.010].Following IPITT,compared with control group,PCOS group showed significantly higher 60 min[(3.12±0.28)mmol/L vs.(2.60±0.28)mmol/L,P=0.031],90 min[(2.62±0.17)mmol/L vs.(2.10±0.33)mmol/L,P=0.026]and 120 min g

关 键 词：多囊卵巢综合征 胰岛素抵抗 白细胞介素-22 胰岛Β细胞 

分 类 号：R711.75[医药卫生—妇产科学]